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Pathoor NN, Ganesh PS, Anshad AR, Gopal RK, Ponmalar EM, Suvaithenamudhan S, Rudrapathy P, Shankar EM. 3-Hydroxybenzoic acid inhibits the virulence attributes and disrupts biofilm production in clinical isolates of Acinetobacter baumannii. Eur J Clin Microbiol Infect Dis 2025; 44:653-669. [PMID: 39739165 DOI: 10.1007/s10096-024-05009-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Accepted: 11/29/2024] [Indexed: 01/02/2025]
Abstract
PURPOSE Acinetobacter baumannii (A. baumannii) is an emerging global public health threat owing to its ability to form biofilms. Here, we evaluated 3-hydroxybenzoic acid (3-HBA), a promising organic compound, for its ability to disrupt biofilm formation and virulence attributes in clinical isolates of A. baumannii. MATERIALS AND METHODS The effect of 3-HBA on A. baumannii was assessed by determining the minimum inhibitory concentration (MIC) and certain other in vitro investigations viz., extracellular polymeric substance (EPS) estimation, crystal violet staining assay, motility assay, and the hydrogen peroxide (H2O2) assay to examine its impact on bacterial virulence. Biofilm formation was also evaluated at the air-liquid interface. In situ visualization investigations were employed to confirm biofilm dispersion at the lowest effective concentration. The cytotoxic effects of 3-HBA on MCF-7 cells were investigated using the MTT assay. RESULTS At a sub-inhibitory concentration of 0.078 mg/mL, 3-HBA reduced biofilm formation in A. baumannii LSAB-04 and A. baumannii LSAB-06 by 61.22% and 59.21%, respectively, and decreased EPS production by 64% in LSAB-04 and 58.31% in LSAB-06. Microscopic examination confirmed significant biofilm dispersion. 3-HBA also significantly impaired swarming motility and increased their sensitivity to H2O2. The MTT assay showed a dose-dependent decrease in MCF-7 cell viability (43.67%) at a concentration of 0.078 mg/mL. CONCLUSION Our findings underscore the likely role of 3-HBA as a promising A. baumannii biofilm-disrupting agent. Further, by downplaying against the virulence factors of A. baumannii, 3-HBA could be a compelling alternative to conventional antibiotics that however requires to be investigated.
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Affiliation(s)
- Naji Naseef Pathoor
- Department of Microbiology, Centre for Infectious Diseases, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University (Deemed to be University), Chennai, 600 077, Tamil Nadu, India
| | - Pitchaipillai Sankar Ganesh
- Department of Microbiology, Centre for Infectious Diseases, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University (Deemed to be University), Chennai, 600 077, Tamil Nadu, India.
| | - Abdul R Anshad
- Infection and Inflammation, Department of Biotechnology, School of Integrative Biology, Central University of Tamil Nadu, Thiruvarur, Tamil Nadu, 610 005, India
| | - Rajesh Kanna Gopal
- Department of Microbiology, Centre for Infectious Diseases, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University (Deemed to be University), Chennai, 600 077, Tamil Nadu, India
| | - Esaki Muthu Ponmalar
- Sri Sairam Siddha Medical College and Research Centre, West Tambaram, Chennai, 600 044, Tamil Nadu, India
| | - Suvaiyarasan Suvaithenamudhan
- Department of Research, Meenakshi Academy of Higher Education and Research (MAHER) (Deemed to be University), Chennai, 600 078, India
| | - Parthiban Rudrapathy
- Microbiology Division, Department of Clinical Laboratory Services and Translational Research, Malabar Cancer Centre (Post Graduate Institute of Oncology Sciences and Research), Thalassery, 670 103, Kerala, India
| | - Esaki M Shankar
- Infection and Inflammation, Department of Biotechnology, School of Integrative Biology, Central University of Tamil Nadu, Thiruvarur, Tamil Nadu, 610 005, India
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Taner F, Baddal B, Theodoridis L, Petrovski S. Biofilm Production in Intensive Care Units: Challenges and Implications. Pathogens 2024; 13:954. [PMID: 39599508 PMCID: PMC11597785 DOI: 10.3390/pathogens13110954] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Revised: 10/23/2024] [Accepted: 10/30/2024] [Indexed: 11/29/2024] Open
Abstract
The prevalence of infections amongst intensive care unit (ICU) patients is inevitably high, and the ICU is considered the epicenter for the spread of multidrug-resistant bacteria. Multiple studies have focused on the microbial diversity largely inhabiting ICUs that continues to flourish despite treatment with various antibiotics, investigating the factors that influence the spread of these pathogens, with the aim of implementing sufficient monitoring and infection control methods. Despite joint efforts from healthcare providers and policymakers, ICUs remain a hub for healthcare-associated infections. While persistence is a unique strategy used by these pathogens, multiple other factors can lead to persistent infections and antimicrobial tolerance in the ICU. Despite the recognition of the detrimental effects biofilm-producing pathogens have on ICU patients, overcoming biofilm formation in ICUs continues to be a challenge. This review focuses on various facets of ICUs that may contribute to and/or enhance biofilm production. A comprehensive survey of the literature reveals the apparent need for additional molecular studies to assist in understanding the relationship between biofilm regulation and the adaptive behavior of pathogens in the ICU environment. A better understanding of the interplay between biofilm production and antibiotic resistance within the environmental cues exhibited particularly by the ICU may also reveal ways to limit biofilm production and indivertibly control the spread of antibiotic-resistant pathogens in ICUs.
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Affiliation(s)
- Ferdiye Taner
- Department of Medical Microbiology and Clinical Microbiology, Faculty of Medicine, Near East University, 99138 Nicosia, Cyprus;
- DESAM Research Institute, Near East University, 99138 Nicosia, Cyprus
| | - Buket Baddal
- Department of Medical Microbiology and Clinical Microbiology, Faculty of Medicine, Near East University, 99138 Nicosia, Cyprus;
- DESAM Research Institute, Near East University, 99138 Nicosia, Cyprus
| | - Liana Theodoridis
- Department of Physiology, Anatomy, and Microbiology, La Trobe University, Bundoora, VIC 3086, Australia; (L.T.); (S.P.)
| | - Steve Petrovski
- Department of Physiology, Anatomy, and Microbiology, La Trobe University, Bundoora, VIC 3086, Australia; (L.T.); (S.P.)
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Jha NK, Gopu V, Sivasankar C, Singh SR, Devi PB, Murali A, Shetty PH. In vitro and in silico assessment of anti-biofilm and anti-quorum sensing properties of 2,4-Di-tert butylphenol against Acinetobacter baumannii. J Med Microbiol 2024; 73. [PMID: 38506718 DOI: 10.1099/jmm.0.001813] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/21/2024] Open
Abstract
Introduction. Acinetobacter baumannii is a nosocomial pathogen with a high potential to cause food-borne infections. It is designated as a critical pathogen by the World Health Organization due to its multi-drug resistance and mortalities reported. Biofilm governs major virulence factors, which promotes drug resistance in A. baumannii. Thus, a compound with minimum selection pressure on the pathogen can be helpful to breach biofilm-related virulence.Hypothesis/Gap Statement. To identify anti-biofilm and anti-virulent metabolites from extracts of wild Mangifera indica (mango) brine pickle bacteria that diminishes pathogenesis and resistance of A. baumannii.Aim. This study reports anti-biofilm and anti-quorum sensing (QS) efficacy of secondary metabolites from bacterial isolates of fermented food origin.Method. Cell-free supernatants (CFS) of 13 bacterial isolates from fermented mango brine pickles were screened for their efficiency in inhibiting biofilm formation and GC-MS was used to identify its metabolites. Anti-biofilm metabolite was tested on early and mature biofilms, pellicle formation, extra polymeric substances (EPS), cellular adherence, motility and resistance of A. baumannii. Gene expression and in silico studies were also carried out to validate the compounds efficacy.Results. CFS of TMP6b identified as Bacillus vallismortis, inhibited biofilm production (83.02 %). Of these, major compound was identified as 2,4-Di-tert-butyl phenol (2,4-DBP). At sub-lethal concentrations, 2,4-DBP disrupted both early and mature biofilm formation. Treatment with 2,4-DBP destructed in situ biofilm formed on glass and plastic. In addition, key virulence traits like pellicle (77.5 %), surfactant (95.3 %), EPS production (3-fold) and cell adherence (65.55 %) reduced significantly. A. baumannii cells treated with 2,4-DBP showed enhanced sensitivity towards antibiotics, oxide radicals and blood cells. Expression of biofilm-concomitant virulence genes like csuA/B, pgaC, pgaA, bap, bfmR, katE and ompA along with QS genes abaI, abaR significantly decreased. The in silico studies further validated the higher binding affinity of 2,4-DBP to the AbaR protein than the cognate ligand molecule.Conclusion. To our knowledge, this is the first report to demonstrate 2,4- DBP has anti-pathogenic potential alone and with antibiotics by in vitro, and in silico studies against A. baumannii. It also indicates its potential use in therapeutics and bio-preservatives.
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Affiliation(s)
- Nisha Kumari Jha
- Department of Food Science and Technology, Pondicherry University, Pondicherry-605014, India
| | - Venkadesaperumal Gopu
- Department of Microbiology and Molecular Genetics, Institute of Medical Research Israel-Canada, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Chandran Sivasankar
- Department of Public Health, College of Veterinary Medicine, Jeonbuk National University, Iksan-54596, Republic of Korea
| | - Satya Ranjan Singh
- Department of Bioinformatics, Pondicherry University, Pondicherry-605014, India
| | - Palanisamy Bruntha Devi
- Department of Food Science and Technology, Pondicherry University, Pondicherry-605014, India
| | - Ayaluru Murali
- Department of Bioinformatics, Pondicherry University, Pondicherry-605014, India
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Apostolaki K, Gagaletsios LA, Papagiannitsis CC, Petinaki E. Macrolides impact the growth ability of clinical Pseudomonas aeruginosa through quorum-sensing systems. J Chemother 2024; 36:24-30. [PMID: 38156440 DOI: 10.1080/1120009x.2023.2296150] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Accepted: 12/12/2023] [Indexed: 12/30/2023]
Abstract
The aim of the present study was to examine the impact of macrolides on the expression of virulence factors and QS-associated genes in clinical P. aeruginosa isolates. Among 60 clinical P. aeruginosa, pyocyanin production was detected in 27 (45%) isolates, which belonged to various STs. Erythromycin inhibited the production of pigments in 12 out of 27 isolates. Other antibiotic categories didn't have an impact on production of pigments. Additionally, results showed that erythromycin sub-MIC inhibited the growth-rate in 17 isolates. Of note, in six isolates, the inhibition of growth-rate was greater when using both erythromycin and meropenem than using each antibiotic individually. Finally, addition of erythromycin down-regulated the expression of QS-associated genes (65.5%-81.3%) and almost all virulence-associated genes. In conclusion, our results confirmed that macrolides could be used in combination with last-line antibiotics, such as carbapenems, to treat infections caused by multidrug-resistant Gram-negative bacteria.
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Affiliation(s)
| | | | | | - Efthimia Petinaki
- Department of Microbiology, University Hospital of Larissa, Larissa, Greece
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Jha RK, Singh E, Khan RJ, Kumar A, Jain M, Muthukumaran J, Singh AK. Droperidol as a potential inhibitor of acyl-homoserine lactone synthase from A. baumannii: insights from virtual screening, MD simulations and MM/PBSA calculations. Mol Divers 2023; 27:1979-1999. [PMID: 36190592 DOI: 10.1007/s11030-022-10533-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Accepted: 09/18/2022] [Indexed: 10/10/2022]
Abstract
Acinetobacter baumannii belongs to the ESKAPE family of pathogens and is a multi-drug resistant, gram-negative bacteria which follows the anaerobic form of respiration. A. baumannii is known to be the causative agent of hospital-related infections such as pneumonia, meningitis, endocarditis, septicaemia and a plethora of infections such as urinary tract infections found primarily in immunocompromised patients. These attributes of A. baumannii make it a priority pathogen against which potential therapeutic agents need to be developed. A. baumannii employs the formation of a biofilm to insulate its colonies from the outer environment, which allows it to grow under harsh environmental conditions and develop resistance against various drug molecules. Acyl-homoserine lactone synthase (AHLS) is an enzyme involved in the quorum-sensing pathway in A. baumannii, which is responsible for the synthesis of signal molecules known as acyl-homoserine lactones, which trigger the signalling pathway to regulate the factors involved in biofilm formation and regulation. The present study utilised a homology-modelled structure of AHLS to virtually screen it against the ZINC in trial/FDA-approved drug molecule library to find a subset of potential lead candidates. These molecules were then filtered based on Lipinski's, toxicological and ADME properties, binding affinity, and interaction patterns to delineate lead molecules. Finally, three promising molecules were selected, and their estimated binding affinity values were corroborated using AutoDock 4.2. The identified molecules and a control molecule were subsequently subjected to MD simulations to mimic the physiological conditions of protein ligand-binding interaction under the influence of a GROMOS forcefield. The global and essential dynamics analyses and MM/PBSA based binding free energy computations suggested Droperidol and Cipargamin as potential inhibitors against the binding site of AHLS from A. baumannii. The binding free energy calculations based on the MM/PBSA method showed excellent results for Droperidol (- 50.02 ± 4.67 kcal/mol) and Cipargamin (- 42.29 ± 4.05 kcal/mol).
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Affiliation(s)
- Rajat Kumar Jha
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, U.P., P.C. 201310, India
| | - Ekampreet Singh
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, U.P., P.C. 201310, India
| | - Rameez Jabeer Khan
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, U.P., P.C. 201310, India
| | - Ankit Kumar
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, U.P., P.C. 201310, India
| | - Monika Jain
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, U.P., P.C. 201310, India
| | - Jayaraman Muthukumaran
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, U.P., P.C. 201310, India.
| | - Amit Kumar Singh
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, U.P., P.C. 201310, India.
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Chiang TT, Huang TW, Sun JR, Kuo SC, Cheng A, Liu CP, Liu YM, Yang YS, Chen TL, Lee YT, Wang YC. Biofilm formation is not an independent risk factor for mortality in patients with Acinetobacter baumannii bacteremia. Front Cell Infect Microbiol 2022; 12:964539. [PMID: 36189355 PMCID: PMC9523115 DOI: 10.3389/fcimb.2022.964539] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Accepted: 08/31/2022] [Indexed: 12/01/2022] Open
Abstract
In the past decades, due to the high prevalence of the antibiotic-resistant isolates of Acinetobacter baumannii, it has emerged as one of the most troublesome pathogens threatening the global healthcare system. Furthermore, this pathogen has the ability to form biofilms, which is another effective mechanism by which it survives in the presence of antibiotics. However, the clinical impact of biofilm-forming A. baumannii isolates on patients with bacteremia is largely unknown. This retrospective study was conducted at five medical centers in Taiwan over a 9-year period. A total of 252 and 459 patients with bacteremia caused by biofilm- and non-biofilm-forming isolates of A. baumannii, respectively, were enrolled. The clinical demographics, antimicrobial susceptibility, biofilm-forming ability, and patient clinical outcomes were analyzed. The biofilm-forming ability of the isolates was assessed using a microtiter plate assay. Multivariate analysis revealed the higher APACHE II score, shock status, lack of appropriate antimicrobial therapy, and carbapenem resistance of the infected strain were independent risk factors of 28-day mortality in the patients with A. baumannii bacteremia. However, there was no significant difference between the 28-day survival and non-survival groups, in terms of the biofilm forming ability. Compared to the patients infected with non-biofilm-forming isolates, those infected with biofilm-forming isolates had a lower in-hospital mortality rate. Patients with either congestive heart failure, underlying hematological malignancy, or chemotherapy recipients were more likely to become infected with the biofilm-forming isolates. Multivariate analysis showed congestive heart failure was an independent risk factor of infection with biofilm-forming isolates, while those with arterial lines tended to be infected with non-biofilm-forming isolates. There were no significant differences in the sources of infection between the biofilm-forming and non-biofilm-forming isolate groups. Carbapenem susceptibility was also similar between these groups. In conclusion, the patients infected with the biofilm-forming isolates of the A. baumannii exhibited different clinical features than those infected with non-biofilm-forming isolates. The biofilm-forming ability of A. baumannii may also influence the antibiotic susceptibility of its isolates. However, it was not an independent risk factor for a 28-day mortality in the patients with bacteremia.
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Affiliation(s)
- Tsung-Ta Chiang
- Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Tzu-Wen Huang
- Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Jun-Ren Sun
- Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
- Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan
| | - Shu-Chen Kuo
- National Institute of Infectious Diseases and Vaccinology, National Health Research Institute, Maoli County, Taiwan
| | - Aristine Cheng
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Chang-Pan Liu
- Division of Infectious Diseases, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan
- Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan
| | - Yuag-Meng Liu
- Division of Infectious Diseases, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Ya-Sung Yang
- Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Te-Li Chen
- Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan
| | - Yi-Tzu Lee
- Department of Emergency Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
- *Correspondence: Yung-Chih Wang, ; Yi-Tzu Lee,
| | - Yung-Chih Wang
- Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
- *Correspondence: Yung-Chih Wang, ; Yi-Tzu Lee,
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Roy S, Chowdhury G, Mukhopadhyay AK, Dutta S, Basu S. Convergence of Biofilm Formation and Antibiotic Resistance in Acinetobacter baumannii Infection. Front Med (Lausanne) 2022; 9:793615. [PMID: 35402433 PMCID: PMC8987773 DOI: 10.3389/fmed.2022.793615] [Citation(s) in RCA: 80] [Impact Index Per Article: 26.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Accepted: 01/31/2022] [Indexed: 07/30/2023] Open
Abstract
Acinetobacter baumannii (A. baumannii) is a leading cause of nosocomial infections as this pathogen has certain attributes that facilitate the subversion of natural defenses of the human body. A. baumannii acquires antibiotic resistance determinants easily and can thrive on both biotic and abiotic surfaces. Different resistance mechanisms or determinants, both transmissible and non-transmissible, have aided in this victory over antibiotics. In addition, the propensity to form biofilms (communities of organism attached to a surface) allows the organism to persist in hospitals on various medical surfaces (cardiac valves, artificial joints, catheters, endotracheal tubes, and ventilators) and also evade antibiotics simply by shielding the bacteria and increasing its ability to acquire foreign genetic material through lateral gene transfer. The biofilm formation rate in A. baumannii is higher than in other species. Recent research has shown how A. baumannii biofilm-forming capacity exerts its effect on resistance phenotypes, development of resistome, and dissemination of resistance genes within biofilms by conjugation or transformation, thereby making biofilm a hotspot for genetic exchange. Various genes control the formation of A. baumannii biofilms and a beneficial relationship between biofilm formation and "antimicrobial resistance" (AMR) exists in the organism. This review discusses these various attributes of the organism that act independently or synergistically to cause hospital infections. Evolution of AMR in A. baumannii, resistance mechanisms including both transmissible (hydrolyzing enzymes) and non-transmissible (efflux pumps and chromosomal mutations) are presented. Intrinsic factors [biofilm-associated protein, outer membrane protein A, chaperon-usher pilus, iron uptake mechanism, poly-β-(1, 6)-N-acetyl glucosamine, BfmS/BfmR two-component system, PER-1, quorum sensing] involved in biofilm production, extrinsic factors (surface property, growth temperature, growth medium) associated with the process, the impact of biofilms on high antimicrobial tolerance and regulation of the process, gene transfer within the biofilm, are elaborated. The infections associated with colonization of A. baumannii on medical devices are discussed. Each important device-related infection is dealt with and both adult and pediatric studies are separately mentioned. Furthermore, the strategies of preventing A. baumannii biofilms with antibiotic combinations, quorum sensing quenchers, natural products, efflux pump inhibitors, antimicrobial peptides, nanoparticles, and phage therapy are enumerated.
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Affiliation(s)
- Subhasree Roy
- Division of Bacteriology, Indian Council of Medical Research (ICMR)-National Institute of Cholera and Enteric Diseases, Kolkata, India
| | - Goutam Chowdhury
- Division of Molecular Microbiology, Indian Council of Medical Research (ICMR)-National Institute of Cholera and Enteric Diseases, Kolkata, India
| | - Asish K. Mukhopadhyay
- Division of Molecular Microbiology, Indian Council of Medical Research (ICMR)-National Institute of Cholera and Enteric Diseases, Kolkata, India
| | - Shanta Dutta
- Division of Bacteriology, Indian Council of Medical Research (ICMR)-National Institute of Cholera and Enteric Diseases, Kolkata, India
| | - Sulagna Basu
- Division of Bacteriology, Indian Council of Medical Research (ICMR)-National Institute of Cholera and Enteric Diseases, Kolkata, India
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Decoding Acinetobacter baumannii biofilm dynamics and associated protein markers: proteomic and bioinformatics approach. Arch Microbiol 2022; 204:200. [PMID: 35239017 DOI: 10.1007/s00203-022-02807-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 01/27/2022] [Accepted: 02/15/2022] [Indexed: 12/11/2022]
Abstract
Biofilm formation by Acinetobacter baumannii is one of the major cause of its persistence in hospital environment. Biofilm phenotypes are more resistant to physical as well as chemical stresses than their planktonic counterparts. The present study was carried in quest of biofilm-associated protein markers and their association with various biological pathways of A. baumannii. The study was designed with an aim to highlight the crucial common factor present in the majority of the A. baumannii strains irrespective of its resistance nature. A label-free proteome comparison of biofilm and planktonic phenotypes of A. baumannii was done using QExactive tandem mass spectrometry. Our investigation suggests key elevation of adhesion factors, acetate metabolism, nutrient transporters, and secretion system proteins are required for biofilm formation in A. baumannii. Elevation of biofilm-associated proteins revealed that biofilm is the unique phenotype with the potential to form robust matrix-embedded colonies and defeat stress condition. Further, core protein markers of biofilm phenotypes could be used as targets for new clinical interventions to combat biofilm-associated infections.
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Gedefie A, Demsis W, Ashagrie M, Kassa Y, Tesfaye M, Tilahun M, Bisetegn H, Sahle Z. Acinetobacter baumannii Biofilm Formation and Its Role in Disease Pathogenesis: A Review. Infect Drug Resist 2021; 14:3711-3719. [PMID: 34531666 PMCID: PMC8439624 DOI: 10.2147/idr.s332051] [Citation(s) in RCA: 152] [Impact Index Per Article: 38.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2021] [Accepted: 09/02/2021] [Indexed: 01/01/2023] Open
Abstract
Acinetobacter species, particularly Acinetobacter baumannii, is the first pathogen on the critical priority list of pathogens for novel antibiotics to become a "red-alert" human pathogen. Acinetobacter baumannii is an emerging global antibiotic-resistant gram-negative bacteria that most typically causes biofilm-associated infections such as ventilator-associated pneumonia and catheter-related infection, both of which are resistant to antibiotic therapy. A. baumannii's capacity to develop antibiotic resistance mechanisms allows the organism to thrive in hospital settings, facilitating the global spread of multidrug-resistant strains. Although Acinetobacter infections are quickly expanding throughout hospital environments around the world, the highest concentration of infections occurs in intensive care units (ICUs). Biofilms are populations of bacteria on biotic or abiotic surfaces that are encased in the extracellular matrix and play a crucial role in pathogenesis, making treatment options more difficult. Even though a variety of biological and environmental elements are involved in the production of A. baumannii biofilms, glucose is the most important component. Biofilm-mediated A. baumannii infections are the most common type of A. baumannii infection associated with medical equipment, and they are extremely difficult to treat. As a result, health care workers (HCWs) should focus on infection prevention and safety actions to avoid A. baumannii biofilm-related infections caused by medical devices, and they should be very selective when using treatments in combination with anti-biofilms. Therefore, this review discusses biofilm formation in A. baumannii, its role in disease pathogenesis, and its antimicrobial resistance mechanism.
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Affiliation(s)
- Alemu Gedefie
- Department of Medical Laboratory Sciences, College of Medicine and Health Science, Wollo University, Dessie, Ethiopia
| | - Wondmagegn Demsis
- Department of Medical Laboratory Sciences, College of Medicine and Health Science, Wollo University, Dessie, Ethiopia
| | - Melaku Ashagrie
- Department of Medical Laboratory Sciences, College of Medicine and Health Science, Wollo University, Dessie, Ethiopia
| | - Yeshimebet Kassa
- Department of Medical Laboratory Sciences, College of Medicine and Health Science, Wollo University, Dessie, Ethiopia
| | - Melkam Tesfaye
- Department of Medical Laboratory Sciences, College of Medicine and Health Science, Wollo University, Dessie, Ethiopia
| | - Mihret Tilahun
- Department of Medical Laboratory Sciences, College of Medicine and Health Science, Wollo University, Dessie, Ethiopia
| | - Habtye Bisetegn
- Department of Medical Laboratory Sciences, College of Medicine and Health Science, Wollo University, Dessie, Ethiopia
| | - Zenawork Sahle
- Department of Medical Laboratory Sciences, Debre Birhan Health Science College, Debre Birhan, Ethiopia
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Josyula A, Parikh KS, Pitha I, Ensign LM. Engineering biomaterials to prevent post-operative infection and fibrosis. Drug Deliv Transl Res 2021; 11:1675-1688. [PMID: 33710589 PMCID: PMC8238864 DOI: 10.1007/s13346-021-00955-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/01/2021] [Indexed: 12/19/2022]
Abstract
Implantable biomaterials are essential surgical devices, extending and improving the quality of life of millions of people globally. Advances in materials science, manufacturing, and in our understanding of the biological response to medical device implantation over several decades have resulted in improved safety and functionality of biomaterials. However, post-operative infection and immune responses remain significant challenges that interfere with biomaterial functionality and host healing processes. The objectives of this review is to provide an overview of the biology of post-operative infection and the physiological response to implanted biomaterials and to discuss emerging strategies utilizing local drug delivery and surface modification to improve the long-term safety and efficacy of biomaterials.
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Affiliation(s)
- Aditya Josyula
- Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA
- Department of Chemical & Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA
| | - Kunal S Parikh
- Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA
- Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
- Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA
- Center for Bioengineering Innovation and Design, Johns Hopkins University, Baltimore, MD, 21218, USA
| | - Ian Pitha
- Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA
- Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
| | - Laura M Ensign
- Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.
- Department of Chemical & Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA.
- Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
- Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA.
- Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, 21287, USA.
- Departments Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
- Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
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11
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Bamunuarachchi NI, Khan F, Kim YM. Inhibition of Virulence Factors and Biofilm Formation of Acinetobacter Baumannii by Naturally-derived and Synthetic Drugs. Curr Drug Targets 2021; 22:734-759. [PMID: 33100201 DOI: 10.2174/1389450121666201023122355] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Revised: 09/17/2020] [Accepted: 09/22/2020] [Indexed: 11/22/2022]
Abstract
Acinetobacter baumannii is a gram-negative, aerobic, non-motile, and pleomorphic bacillus. A. baumannii is also a highly-infectious pathogen causing high mortality and morbidity rates in intensive care units. The discovery of novel agents against A. baumannii infections is urgently needed due to the emergence of drug-resistant A. baumannii strains and the limited number of efficacious antibiotics available for treatment. In addition to the production of several virulence factors, A. baumannii forms biofilms on the host cell surface as well. Formation of biofilms occurs through initial surface attachment, microcolony formation, biofilm maturation, and detachment stages, and is one of the major drug resistance mechanisms employed by A. baumannii. Several studies have previously reported the efficacy of naturally-derived and synthetic compounds as anti- biofilm and anti-virulence agents against A. baumannii. Here, inhibition of biofilm formation and virulence factors of A. baumannii using naturally-derived and synthetic compounds are reviewed.
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Affiliation(s)
| | - Fazlurrahman Khan
- Institute of Food Science, Pukyong National University, Busan 48513, South Korea
| | - Young-Mog Kim
- Department of Food Science and Technology, Pukyong National University, Busan 48513, South Korea
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12
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Efficacy of isolated bacteriophage against biofilm embedded colistin-resistant Acinetobacter baumannii. GENE REPORTS 2021. [DOI: 10.1016/j.genrep.2020.100984] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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13
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Elkhatib WF, Khalil MAF, Ashour HM. Integrons and Antiseptic Resistance Genes Mediate Resistance of Acinetobacter baumannii and Pseudomonas aeruginosa Isolates from Intensive Care Unit Patients with Wound Infections. Curr Mol Med 2020; 19:286-293. [PMID: 30907313 DOI: 10.2174/1566524019666190321113008] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Revised: 03/12/2019] [Accepted: 03/18/2019] [Indexed: 11/22/2022]
Abstract
BACKGROUND Acinetobacter baumannii and Pseudomonas aeruginosa are of major concern for hospitalized patients. METHODS We evaluated antibiotic and antiseptic resistance of A. baumannii (n = 29) and P. aeruginosa (n = 37) isolates recovered from 66 intensive care unit (ICU) patients and determined the prevalence of qacE, qacEΔ1, and integrons in these clinical isolates. Antibiotic and antiseptic susceptibility testing was performed via Kirby Bauer disk diffusion and broth microdilution methods, respectively. The resistance genes and integrons were detected by PCR. A. baumannii and P. aeruginosa ICU isolates showed 100% and 70.3% antibiotic multiple drug resistance patterns, respectively. RESULTS The isolates also revealed high levels of resistance (MIC ≥ 16 µg/ml) against antiseptics commonly used in Egyptian hospitals (Benzalkonium, Benzethonium, and Chlorhexidine). The qacEΔ1 gene showed higher levels of prevalence in both A. baumannii and P. aeruginosa isolates (93.5% and 78%, respectively) as compared to that of qacE gene (52.0% and 33.0%, respectively). The intI1 was more prevalent among A. baumannii isolates (65.5%) compared to P. aeruginosa isolates (37.8%). P. aeruginosa resistance genotypes were significantly associated with antibiotic and antiseptic resistance patterns. A. baumannii resistance genotypes were associated with antiseptic-resistance patterns. CONCLUSION The excessive usage of antiseptics may escalate bacterial resistance, especially with high prevalence of intI1 integron in these pathogens.
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Affiliation(s)
- Walid F Elkhatib
- Department of Microbiology and Immunology, School of Pharmacy & Pharmaceutical Industries, Badr University in Cairo (BUC), Entertainment Area, Badr City, Cairo, Egypt.,Microbiology and Immunology Department, Faculty of Pharmacy, Ain Shams University, African Union Organization St., Abbassia, Cairo11566, Egypt
| | - Mahmoud A F Khalil
- Department of Microbiology and Immunology, Faculty of Pharmacy, Fayoum University, Fayoum City, Egypt
| | - Hossam M Ashour
- Department of Biological Sciences, College of Arts and Sciences, University of South Florida St. Petersburg, St. Petersburg, Florida, United States.,Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, Egypt
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14
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Shakerimoghaddam A, Razavi D, Rahvar F, Khurshid M, Ostadkelayeh SM, Esmaeili SA, Khaledi A, Eshraghi M. Evaluate the Effect of Zinc Oxide and Silver Nanoparticles on Biofilm and icaA Gene Expression in Methicillin-Resistant Staphylococcus aureus Isolated From Burn Wound Infection. J Burn Care Res 2020; 41:1253-1259. [PMID: 32479611 DOI: 10.1093/jbcr/iraa085] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Methicillin-resistant Staphylococcus aureus is the cause of nosocomial and community-acquired infections. This study aimed to evaluate the effect of zinc oxide and silver nanoparticles (ZnO-Ag NPs) on biofilms formation and icaA gene expression in methicillin-resistant S. aureus (MRSA). In this study, three standard strains (ATCC 43300, 25923, and 29913) and a clinical isolate are included. The minimum inhibitory concentration (MIC) of nanoparticles was determined by microdilution broth method. The antibacterial effects of ZnO-Ag NPs either alone or in combination with each other were compared with vancomycin (as the control group). The effect of MIC and sub-MIC concentrations of ZnO-Ag NPs on biofilm formation was determined by the microtiter plate method. The expression level of the icaA gene was assessed by real-time PCR LightCycler® 96 software (Version 1.1.0.1320, Roche, Germany). technique. All experiments were repeated three times. Data were analyzed using SPSS software through ANOVA and t-test. The P-value of less than .05 was considered as statistically significant. The average MICs of ZnO, Ag, and ZnO-Ag NPs compounds were 393.2, 179.8, and 60.8 μg/ml, respectively. The compound of ZnO-Ag NPs had a synergistic effect against all isolates. ZnO-Ag NPs decreased the biofilm formation rate at MIC and sub-MIC concentrations (P < .001). Sub-MIC ZnO-Ag NPs concentration significantly reduced the icaA gene expression in S. aureus strains (P < .03). The sub-MIC concentration of ZnO-Ag NPs reduced biofilm formation rate and icaA gene expression in Staphylococcus aureus strains compared with vancomycin. It can be used to cover medical devices after examining more clinical isolates to prevent bacterial colonization.
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Affiliation(s)
- Ali Shakerimoghaddam
- Infectious Diseases, Research Center, Kashan University of Medical Sciences, Iran.,Department of Microbiology and Immunology, Faculty of Medicine, Kashan University of Medical Sciences, Iran
| | - Delaramsadat Razavi
- Biology Department, Sciences Faculty, Science and Arts University, Yazd, Iran
| | - Farzaneh Rahvar
- Department of Medical Genetics, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology(NIGEB), Tehran, Iran
| | - Maria Khurshid
- Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Seyed-Alireza Esmaeili
- Immunology Research Center, Mashhad University of Medical Sciences, Iran.,Immunology Department, Faculty of Medicine, Mashhad University of Medical Sciences, Iran
| | - Azad Khaledi
- Infectious Diseases, Research Center, Kashan University of Medical Sciences, Iran.,Department of Microbiology and Immunology, Faculty of Medicine, Kashan University of Medical Sciences, Iran
| | - Mohsen Eshraghi
- Department of Thoracic Surgery, Qom University of Medical Sciences, Iran
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15
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Colquhoun JM, Rather PN. Insights Into Mechanisms of Biofilm Formation in Acinetobacter baumannii and Implications for Uropathogenesis. Front Cell Infect Microbiol 2020; 10:253. [PMID: 32547965 PMCID: PMC7273844 DOI: 10.3389/fcimb.2020.00253] [Citation(s) in RCA: 69] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2020] [Accepted: 04/30/2020] [Indexed: 01/10/2023] Open
Abstract
Multidrug resistant Acinetobacter baumannii is a serious healthcare threat. In fact, the Center for Disease Control recently reported that carbapenem-resistant A. baumannii is responsible for more than 8,500 infections, 700 deaths, and $281 million in healthcare costs annually in the United States with few, if any, treatment options available, leading to its designation as a pathogen of urgent concern and a priority for novel antimicrobial development. It is hypothesized that biofilms are, at least in part, responsible for the high prevalence of A. baumannii nosocomial and recurrent infections because they frequently contaminate hospital surfaces and patient indwelling devices; therefore, there has been a recent push for mechanistic understanding of biofilm formation, maturation and dispersal. However, most research has focused on A. baumannii pneumonia and bloodstream infections, despite a recent retrospective study showing that 17.1% of A. baumannii isolates compiled from clinical studies over the last two decades were obtained from urinary samples. This highlights that A. baumannii is an underappreciated uropathogen. The following minireview will examine our current understanding of A. baumannii biofilm formation and how this influences urinary tract colonization and pathogenesis.
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Affiliation(s)
- Jennifer M Colquhoun
- Department of Microbiology and Immunology, Emory University, Atlanta, GA, United States
| | - Philip N Rather
- Department of Microbiology and Immunology, Emory University, Atlanta, GA, United States.,Research Service, Atlanta VA Healthcare System, Decatur, GA, United States
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16
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Genteluci GL, Gomes DBC, Pereira D, Neves MDC, de Souza MJ, Rangel K, Villas Bôas MHS. Multidrug-resistant Acinetobacter baumannii: differential adherence to HEp-2 and A-549 cells. Braz J Microbiol 2020; 51:657-664. [PMID: 32180159 DOI: 10.1007/s42770-020-00252-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2018] [Accepted: 02/28/2020] [Indexed: 12/16/2022] Open
Abstract
Acinetobacter baumannii has been associated with antimicrobial resistance and ability to form biofilms. Furthermore, its adherence to host cells is an important factor to the colonization process. Therefore, this study intended to identify some virulence factors that can explain the success of A. baumannii in causing nosocomial infections. We studied 92 A. baumannii isolates collected from hospitals in Rio de Janeiro, Brazil. Isolates were identified and the susceptibility to antimicrobials was determined. Oxacilinase type β-lactamase encoding genes were amplified by polymerase chain reaction, and genetic diversity was investigated by pulsed-field gel electrophoresis (PFGE). In addition, biofilm formation on polystyrene plates using crystal violet staining was quantified, and adherence to human cell lines was evaluated. Eighty-six isolates were multidrug-resistant, of which 93% were carbapenem-resistant. All isolates had the blaOXA-51 gene and 94% had the blaOXA-23 gene, other searched blaOXA genes were not detected. PFGE typing showed two predominant clones, and biofilm production was observed in 79% of isolates. A. baumannii isolates adhered better to HEp-2 cell compared with A-549 cell. Clones A, B, E, and F showed a significantly increased adherence to HEp-2 compared with adherence to A-549 cell. Our findings revealed that A. baumannii isolates had high frequencies of resistance to antimicrobial agents, ability to form biofilm, and capacity to adhere to HEp-2 cells.
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Affiliation(s)
- Gabrielle Limeira Genteluci
- Department of Microbiology, National Institute of Quality Control in Heath, Fiocruz, Rio de Janeiro, Brazil.
- Post-Graduation Program in Health Surveillance, Fiocruz, National Institute of Quality Control in Heath, Rio de Janeiro, Brazil.
| | - Daniela Betzler Cardoso Gomes
- Department of Microbiology, National Institute of Quality Control in Heath, Fiocruz, Rio de Janeiro, Brazil
- Post-Graduation Program in Health Surveillance, Fiocruz, National Institute of Quality Control in Heath, Rio de Janeiro, Brazil
| | - Daniella Pereira
- Department of Microbiology, National Institute of Quality Control in Heath, Fiocruz, Rio de Janeiro, Brazil
| | - Marta de Campos Neves
- Department of Microbiology, National Institute of Quality Control in Heath, Fiocruz, Rio de Janeiro, Brazil
| | | | - Karyne Rangel
- Department of Microbiology, National Institute of Quality Control in Heath, Fiocruz, Rio de Janeiro, Brazil
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17
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Insights into Antagonistic Interactions of Multidrug Resistant Bacteria in Mangrove Sediments from the South Indian State of Kerala. Microorganisms 2019; 7:microorganisms7120678. [PMID: 31835720 PMCID: PMC6956087 DOI: 10.3390/microorganisms7120678] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2019] [Revised: 12/06/2019] [Accepted: 12/09/2019] [Indexed: 01/28/2023] Open
Abstract
Antibiotic resistance is a global issue which is magnified by interspecies horizontal gene transfer. Understanding antibiotic resistance in bacteria in a natural setting is crucial to check whether they are multidrug resistant (MDR) and possibly avoid outbreaks. In this study, we have isolated several antibiotic-resistant bacteria (ARB) (n = 128) from the mangroves in Kerala, India. ARBs were distributed based on antibiotics (p = 1.6 × 10-5). The 16S rRNA gene characterization revealed dominance by Bacillaceae (45%), Planococcaceae (22.5%), and Enterobacteriaceae (17.5%). A high proportion of the isolates were MDR (75%) with maximum resistance to methicillin (70%). Four isolates affiliated to plant-growth promoters, probiotics, food, and human pathogens were resistant to all antibiotics indicating the seriousness and prevalence of MDR. A significant correlation (R = 0.66; p = 2.5 × 10-6) was observed between MDR and biofilm formation. Antagonist activity was observed in 62.5% isolates. Gram-positive isolates were more susceptible to antagonism (75.86%) than gram-negative (36.36%) isolates. Antagonism interactions against gram-negative isolates were lower (9.42%) when compared to gram-positive isolates (89.85%). Such strong antagonist activity can be harnessed for inspection of novel antimicrobial mechanisms and drugs. Our study shows that MDR with strong biofilm formation is prevalent in natural habitat and if acquired by deadly pathogens may create havoc in public health.
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18
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Virulence genes profile and biofilm formation ability of Acinetobacter baumannii strains isolated from inpatients of a tertiary care hospital in southwest of Iran. GENE REPORTS 2019. [DOI: 10.1016/j.genrep.2019.100481] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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19
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In-Vitro Biofilm Formation and Antimicrobial Resistance of Escherichia coli in Diabetic and Nondiabetic Patients. BIOMED RESEARCH INTERNATIONAL 2019; 2019:1474578. [PMID: 31641666 PMCID: PMC6770373 DOI: 10.1155/2019/1474578] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/29/2019] [Revised: 07/23/2019] [Accepted: 08/05/2019] [Indexed: 01/11/2023]
Abstract
Background Diabetic patients are more susceptible to urinary tract infection compared to nondiabetic patients, Escherichia coli being the most common uropathogen causing UTI. Unreasonable and incorrect antibiotic prescription for UTI in these patients may induce the development of antibiotic-resistant urinary pathogens resulting in delayed recovery and longer hospitalization. In addition to these, biofilm forming capacity of the pathogen may worsen the problem. The main aim of this cross-sectional study (conducted from March to September 2015) is to detect the biofilm forming capacity of UTI causing micro-organisms and compare the antibiotic resistance pattern of Escherichia coli, the most common cause of UTI, which will help the physician in choosing the best antibiotic. Method Total of 1,099 clean-catch mid stream urine (CCMSU) was processed by standard microbiological technique; 182 were from the diabetic group and 917 nondiabetic. Following identification, all isolates were subjected to antibiotic susceptibility testing using modified Kirby-Bauer disc diffusion method. In-vitro biofilm forming capacity of the isolates were detected by Microtitre plate method. The data were analyzed using SPSS software 16. Result Urinary tract infection was found to be significantly higher in diabetic patients (42.9%) compared to nondiabetic patients (17.4%) with Escherichia coli as the most common uropathogen in both diabetic and nondiabetic groups. Similarly, UTI was more common in elderly population (29.5%). Imipenem, nitrofurantoin and amikacin were found to be the most effective drug for uropathogenic E. coli in both diabetic and nondiabetic patients, whereas amoxicillin, ciprofloxacin, and cotrimoxazole were least effective. Of the total bacterial isolates, 43.3% showed positive results for in-vitro biofilm production by the Microtitre plate method. A significantly higher resistance rate was observed among biofilm producing E. coli for quinolones, cotrimoxazole, and third generation cephalosporin ceftriaxone. Most of the biofilm producers (79.5%) were found to be MDR (p-value 0.015). Conclusion Elderly populations with diabetes are at a higher risk of UTI. Higher biofilm production and resistance to in-use antimicrobial agents in this study render its inefficacy for empirical treatment and point out the importance of biofilm screening to ensure the effective management of infection.
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20
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In Vitro Anti-Biofilm Activity of Curcumin Nanoparticles in Acinetobacter baumannii: A Culture-Based and Molecular Approach. ARCHIVES OF CLINICAL INFECTIOUS DISEASES 2019. [DOI: 10.5812/archcid.83263] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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21
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Saipriya K, Swathi CH, Ratnakar KS, Sritharan V. Quorum-sensing system in Acinetobacter baumannii: a potential target for new drug development. J Appl Microbiol 2019; 128:15-27. [PMID: 31102552 DOI: 10.1111/jam.14330] [Citation(s) in RCA: 85] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2019] [Revised: 04/24/2019] [Accepted: 05/14/2019] [Indexed: 12/30/2022]
Abstract
Acinetobacter baumannii causes several nosocomial infections and poses major threat when it is multidrug resistant. Even pan drug-resistant strains have been reported in some countries. The intensive care unit (ICU) mortality rate ranged from 45.6% to 60.9% and it is as high as 84.3% when ventilator-associated pneumonia was caused by XDR (extensively drug resistant) A. baumannii. Acinetobacter baumannii constituted 9.4% of all Gram-negative organisms throughout the hospital and 22.6% in the ICUs according to a study carried out in an Indian hospital. One of the major factors contributing to drug resistance in A. baumannii infections is biofilm development. Quorum sensing (QS) facilitates biofilm formation and therefore the search for 'quorum quenchers' has increased recently. Such compounds are expected to inhibit biofilm formation and hence reduce/prevent development of drug resistance in the bacteria. Some of these compounds also target synthesis of some virulence factors (VF). Several candidate drugs have been identified and are at various stages of drug development. Since quorum quenching, inhibition of biofilm formation and inhibition of VF synthesis do not pose any threat to the DNA replication and cell division of the bacteria, chances of resistance development to such compounds is presumably rare. Thus, these compounds ideally qualify as adjunct therapeutics and could be administered along with an antibiotic to reduce chances of resistance development and also to increase the effectiveness of antimicrobial therapy. This review describes the state-of-art in QS process in Gram-negative bacteria in general and in A. baumannii in particular. This article elaborates the nature of QS mediators, their characteristics, and the methods for their detection and quantification. Various potential sites in the QS pathway have been highlighted as drug targets and the candidate quorum quenchers which inhibit the mediator's synthesis or function are enlisted.
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Affiliation(s)
- K Saipriya
- Department of Molecular Diagnostics & Biomarkers, Global Medical Education & Research Foundation (GMERF), Lakdi-Ka-Pul, Hyderabad, India
| | - C H Swathi
- Department of Molecular Diagnostics & Biomarkers, Global Medical Education & Research Foundation (GMERF), Lakdi-Ka-Pul, Hyderabad, India
| | - K S Ratnakar
- Department of Molecular Diagnostics & Biomarkers, Global Medical Education & Research Foundation (GMERF), Lakdi-Ka-Pul, Hyderabad, India
| | - V Sritharan
- Department of Molecular Diagnostics & Biomarkers, Global Medical Education & Research Foundation (GMERF), Lakdi-Ka-Pul, Hyderabad, India
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22
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Lopez-Gigosos RM, Mariscal A, Gutierrez-Bedmar M, Real M, Mariscal-López E. Carbapenem resistance in Acinetobacter baumannii is associated with enhanced survival on hospital fabrics. Acta Microbiol Immunol Hung 2019; 66:143-154. [PMID: 30403362 DOI: 10.1556/030.65.2018.043] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
The success of Acinetobacter baumannii as an emerging organism is probably linked to its high resistance to adverse environmental conditions. This study was conducted to analyze the association between some factors that may favor the dissemination of A. baumannii clinical isolates. A total of 47 clinical strains of A. baumannii were evaluated to carbapenem, the ability to produce biofilm, the susceptibility to some antiseptics, and the survival time on cotton fabrics. Most of the isolates were resistant to carbapenem (72.3%), produced biofilm (83%), and survived more than 7 (51%) days on fabrics. A significant association between decreased susceptibility to antiseptics containing chlorhexidine or triclosan and carbapenem resistance and survival on fabrics could be observed. The resistance to carbapenem was significantly associated with survival on fabric, but not with the ability to form biofilm. The survival of the isolates on fabric was not associated with the ability to produce biofilms. Characteristics, such as resistance to antibiotics, ability to form biofilm, and survival on dry surfaces, probably contribute to the proliferation of this organism when selected in the hospital environment and can partly explain its success as responsible for nosocomial infection.
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Affiliation(s)
| | - Alberto Mariscal
- 1 Department of Public Health and Psychiatry, Malaga University, Malaga, Spain
| | | | - Macarena Real
- 1 Department of Public Health and Psychiatry, Malaga University, Malaga, Spain
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23
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Zhang M, Wang L, Xu M, Zhou H, Wang S, Wang Y, Bai M, Zhang C. Selective antibiotic resistance genes in multiphase samples during biofilm growth in a simulated drinking water distribution system: Occurrence, correlation and low-pressure ultraviolet removal. THE SCIENCE OF THE TOTAL ENVIRONMENT 2019; 649:146-155. [PMID: 30172134 DOI: 10.1016/j.scitotenv.2018.08.297] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/23/2018] [Revised: 08/22/2018] [Accepted: 08/22/2018] [Indexed: 06/08/2023]
Abstract
The aim of this study was to gain comprehensive insights into the characteristics of antibiotic resistance genes (ARGs) in multiphase samples from drinking water distribution pipelines using a simulated biofilm reactor. During 120 d of continuous operation, common parameters and six ARGs (ermA, ermB, aphA2, ampC, sulII, and tetO) in samples of three phases (water, particle, and biofilm) from the reactor were investigated, which demonstrated secondary contamination by ARGs. Abundances of the six ARGs in the reactor effluent increased gradually, and in the 120 d effluent, the relative abundances of aphA2 and sulII were the highest, at 9.9 × 10-4 and 1.3 × 10-3, respectively, with a 1.5-fold and 2.8-fold increase, compared with those in the influent. The relative abundances of the six ARGs in the biofilm phase increased significantly (P < 0.05) at 120 d, which was caused by robust bacteria in biofilm that was newly exposed following the detachment of a large piece of aging biofilm. In the particle phase, four of the ARGs did not change significantly during the 120 d period. The six ARGs in the samples of three phases showed a negative correlation with residual chlorine in the pipe water, which demonstrated that low abundance of ARGs in the samples of three phases was related to the improvement of residual chlorine. The proportion of cultivable bacteria illustrated that the robust and active bacteria were negatively correlated with the six ARGs in the biofilm. Total organic carbon (TOC) in the pipeline showed a positive correlation with the proportion of cultivable bacteria in both the water and biofilm phases, which indicated that a TOC reduction in the pipeline contributed to low abundance of ARGs. With low-pressure ultraviolet (LP-UV) irradiation of 20 mJ/cm2, ARGs in the samples of three phases were efficiently controlled, which showed that LP-UV can be used for ARG removal in terminal water for supplemental bactericidal treatment of pipeline effluent.
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Affiliation(s)
- Minglu Zhang
- Department of Environmental Science and Engineering, Beijing Technology and Business University, Beijing 100048, China
| | - Li Wang
- Department of Environmental Science and Engineering, Beijing Technology and Business University, Beijing 100048, China
| | - Mengyao Xu
- Department of Environmental Science and Engineering, Beijing Technology and Business University, Beijing 100048, China
| | - He Zhou
- Beijing Boda Water Company, Beijing 100176, China
| | - Shuangling Wang
- Department of Environmental Science and Engineering, Beijing Technology and Business University, Beijing 100048, China
| | - YongJing Wang
- Department of Environmental Science and Engineering, Beijing Technology and Business University, Beijing 100048, China
| | - Miao Bai
- Institute of Disease Control and Prevention of Chinese PLA, Beijing 100071, China
| | - Can Zhang
- Institute of Disease Control and Prevention of Chinese PLA, Beijing 100071, China.
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24
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Beganovic M, Luther MK, Daffinee KE, LaPlante KL. Biofilm prevention concentrations (BPC) of minocycline compared to polymyxin B, meropenem, and amikacin against Acinetobacter baumannii. Diagn Microbiol Infect Dis 2019; 94:223-226. [PMID: 30827805 DOI: 10.1016/j.diagmicrobio.2019.01.016] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2018] [Revised: 12/03/2018] [Accepted: 01/21/2019] [Indexed: 11/29/2022]
Abstract
Infections caused by Acinetobacter baumannii are difficult to treat as they are often multidrug resistant (MDR) and frequently form biofilms. We investigated the activities of minocycline, polymyxin B, meropenem, and amikacin against diverse Acinetobacter baumannii strains with biofilm formation classified as weak versus moderate/strong. At clinically achievable concentrations, minocycline prevented biofilm formation for 96% of isolates versus 54% for polymyxin B, 29% for meropenem and 29% for amikacin. Minocycline and polymyxin B demonstrated highest in vitro activity against A. baumannii and prevented biofilm formation for a majority of isolates.
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Affiliation(s)
- Maya Beganovic
- Infectious Diseases Research Program, Providence Veterans Affairs Medical Center, Providence, RI, United States; College of Pharmacy, University of Rhode Island, Kingston, RI, United States
| | - Megan K Luther
- Infectious Diseases Research Program, Providence Veterans Affairs Medical Center, Providence, RI, United States; College of Pharmacy, University of Rhode Island, Kingston, RI, United States; Center of Innovation in Long-Term Support Services, Providence Veterans Affairs Medical Center, Providence, RI, United States
| | - Kathryn E Daffinee
- Infectious Diseases Research Program, Providence Veterans Affairs Medical Center, Providence, RI, United States
| | - Kerry L LaPlante
- Infectious Diseases Research Program, Providence Veterans Affairs Medical Center, Providence, RI, United States; College of Pharmacy, University of Rhode Island, Kingston, RI, United States; Center of Innovation in Long-Term Support Services, Providence Veterans Affairs Medical Center, Providence, RI, United States; Warren Alpert Medical School of Brown University, Division of Infectious Diseases, Providence, RI.
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Dumaru R, Baral R, Shrestha LB. Study of biofilm formation and antibiotic resistance pattern of gram-negative Bacilli among the clinical isolates at BPKIHS, Dharan. BMC Res Notes 2019; 12:38. [PMID: 30658694 PMCID: PMC6339267 DOI: 10.1186/s13104-019-4084-8] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2018] [Accepted: 01/14/2019] [Indexed: 01/31/2023] Open
Abstract
Objectives Gram-negative bacilli are the common causative agents for community-acquired, nosocomial and opportunistic infections. The recent upsurge of biofilm, as well as beta-lactamases producing strains, have synergistically led to the extensive dissemination of multi-drug resistant gram-negative bacilli. This study was carried out with an intention to detect the biofilm formation by gram-negative bacilli and determine their antibiogram along with the detection of extended-spectrum beta-lactamases (ESBLs) and metallo-beta-lactamases (MBLs) production. Results Among 314 isolates, Escherichia coli (38%) were the predominant isolates followed by Acinetobacter spp. (20%), Klebsiella spp. (16%), and Pseudomonas spp. (12%). Overall, 197 (62.73%) of isolates were biofilm positive. 84 (26.75%) and 51 (16.24%) were confirmed as ESBL and MBL producers respectively. The association between MBL production and biofilm formation was statistically significant (χ2 = 10.20, P value= 0.002) whereas it was insignificant between ESBL and biofilm production (χ2 = 0.006, P-value= 0.937). Most of the biofilm and MBL producing strains were multi-drug resistant.
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Affiliation(s)
- Rabina Dumaru
- Microbiology & Infectious Diseases, B.P Koirala Institute of Health Sciences, Dharan, 56700, Nepal.
| | - Ratna Baral
- Microbiology & Infectious Diseases, B.P Koirala Institute of Health Sciences, Dharan, 56700, Nepal
| | - Lok Bahadur Shrestha
- Microbiology & Infectious Diseases, B.P Koirala Institute of Health Sciences, Dharan, 56700, Nepal
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Shi C, Li M, Muhammad I, Ma X, Chang Y, Li R, Li C, He J, Liu F. Combination of berberine and ciprofloxacin reduces multi-resistant Salmonella strain biofilm formation by depressing mRNA expressions of luxS, rpoE, and ompR. J Vet Sci 2018; 19:808-816. [PMID: 30304890 PMCID: PMC6265579 DOI: 10.4142/jvs.2018.19.6.808] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2018] [Revised: 09/13/2018] [Accepted: 10/01/2018] [Indexed: 12/30/2022] Open
Abstract
Bacterial biofilms have been demonstrated to be closely related to clinical infections and contribute to drug resistance. Berberine, which is the main component of Coptis chinensis, has been reported to have efficient antibacterial activity. This study aimed to investigate the potential effect of a combination of berberine with ciprofloxacin (CIP) to inhibit Salmonella biofilm formation and its effect on expressions of related genes (rpoE, luxS, and ompR). The fractional inhibitory concentration (FIC) index of the combination of berberine with CIP is 0.75 showing a synergistic antibacterial effect. The biofilm's adhesion rate and growth curve showed that the multi-resistant Salmonella strain had the potential to form a biofilm relative to that of strain CVCC528, and the antibiofilm effects were in a dose-dependent manner. Biofilm microstructures were rarely observed at 1/2 × MIC/FIC concentrations (MIC, minimal inhibition concentration), and the combination had a stronger antibiofilm effect than each of the antimicrobial agents used alone at 1/4 × FIC concentration. LuxS, rpoE, and ompR mRNA expressions were significantly repressed (p ＜ 0.01) at 1/2 × MIC/FIC concentrations, and the berberine and CIP combination repressed mRNA expressions more strongly at the 1/4 × FIC concentration. The results indicate that the combination of berberine and CIP has a synergistic effect and is effective in inhibiting Salmonella biofilm formation via repression of luxS, rpoE, and ompR mRNA expressions.
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Affiliation(s)
- Chenxi Shi
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China
- Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Harbin 150030, China
| | - Minmin Li
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China
- Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Harbin 150030, China
| | - Ishfaq Muhammad
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China
- Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Harbin 150030, China
| | - Xin Ma
- Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150069, China
| | - Yicong Chang
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China
- Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Harbin 150030, China
| | - Rui Li
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China
- Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Harbin 150030, China
| | - Changwen Li
- Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150069, China
| | - Jingshan He
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China
- Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Harbin 150030, China
| | - Fangping Liu
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China
- Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Harbin 150030, China
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Antibacterial and Antibiofilm Activity and Mode of Action of Magainin 2 against Drug-Resistant Acinetobacter baumannii. Int J Mol Sci 2018; 19:ijms19103041. [PMID: 30301180 PMCID: PMC6213043 DOI: 10.3390/ijms19103041] [Citation(s) in RCA: 67] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2018] [Revised: 09/28/2018] [Accepted: 09/28/2018] [Indexed: 02/06/2023] Open
Abstract
Antimicrobial peptides (AMPs) are promising therapeutic agents for treating antibiotic-resistant bacterial infections. Previous studies showed that magainin 2 (isolated from African clawed fogs Xenopus laevis) has antimicrobial activity against gram-positive and gram-negative bacteria. The present study was conducted to investigate the antibacterial activity of magainin 2 against Acinetobacter baumannii. Magainin 2 showed excellent antibacterial activity against A. baumannii strains and high stability at physiological salt concentrations. This peptide was not cytotoxic towards HaCaT cells and showed no hemolytic activity. Biofilm inhibition and elimination were significantly induced in all A. baumannii strains exposed to magainin 2. We confirmed the mechanism of magainin 2 on the bacterial outer and inner membranes. Collectively, these results suggest that magainin 2 is an effective antimicrobial and antibiofilm agent against A. baumannii strains.
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Association of Antibiotic Resistance, Cell Adherence, and Biofilm Production with the Endemicity of Nosocomial Klebsiella pneumoniae. BIOMED RESEARCH INTERNATIONAL 2018; 2018:7012958. [PMID: 30345305 PMCID: PMC6174813 DOI: 10.1155/2018/7012958] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/17/2018] [Accepted: 07/31/2018] [Indexed: 11/17/2022]
Abstract
Klebsiella pneumoniae is a leading cause of multiple nosocomial infections, some of which are associated with high mortality. The increasing prevalence of antibiotic-resistant strains highlights their clinical importance and how complicated managing treatment can be. In this study, we investigated antimicrobial resistance, cell adherence, and biofilm production of nosocomial K. pneumoniae strains isolated from surveillance studies in a Mexican tertiary hospital and evaluated the potential association of these phenotypes with endemicity. The great majority of the clones exhibited adhesion to cultured epithelial cells and were strong biofilm producers. A direct relationship between adhesion phenotypes, biofilm production, and endemicity was not always apparent. Biofilm formation and production of ESBL did not appear to be directly associated. Notably, all the endemic strains were multidrug-resistant. This study emphasizes that while endemic strains possess various virulence-associated properties, antimicrobial resistance appears to be a determining factor of their endemicity.
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Magana M, Sereti C, Ioannidis A, Mitchell CA, Ball AR, Magiorkinis E, Chatzipanagiotou S, Hamblin MR, Hadjifrangiskou M, Tegos GP. Options and Limitations in Clinical Investigation of Bacterial Biofilms. Clin Microbiol Rev 2018; 31:e00084-16. [PMID: 29618576 PMCID: PMC6056845 DOI: 10.1128/cmr.00084-16] [Citation(s) in RCA: 118] [Impact Index Per Article: 16.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Bacteria can form single- and multispecies biofilms exhibiting diverse features based upon the microbial composition of their community and microenvironment. The study of bacterial biofilm development has received great interest in the past 20 years and is motivated by the elegant complexity characteristic of these multicellular communities and their role in infectious diseases. Biofilms can thrive on virtually any surface and can be beneficial or detrimental based upon the community's interplay and the surface. Advances in the understanding of structural and functional variations and the roles that biofilms play in disease and host-pathogen interactions have been addressed through comprehensive literature searches. In this review article, a synopsis of the methodological landscape of biofilm analysis is provided, including an evaluation of the current trends in methodological research. We deem this worthwhile because a keyword-oriented bibliographical search reveals that less than 5% of the biofilm literature is devoted to methodology. In this report, we (i) summarize current methodologies for biofilm characterization, monitoring, and quantification; (ii) discuss advances in the discovery of effective imaging and sensing tools and modalities; (iii) provide an overview of tailored animal models that assess features of biofilm infections; and (iv) make recommendations defining the most appropriate methodological tools for clinical settings.
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Affiliation(s)
- Maria Magana
- Department of Clinical Microbiology, Athens Medical School, Aeginition Hospital, Athens, Greece
| | - Christina Sereti
- Department of Clinical Microbiology, Athens Medical School, Aeginition Hospital, Athens, Greece
- Department of Microbiology, Thriassio General Hospital, Attiki, Greece
| | - Anastasios Ioannidis
- Department of Clinical Microbiology, Athens Medical School, Aeginition Hospital, Athens, Greece
- Department of Nursing, Faculty of Human Movement and Quality of Life Sciences, University of Peloponnese, Sparta, Greece
| | - Courtney A Mitchell
- Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, Tennessee, USA
| | - Anthony R Ball
- Gliese 623b, Mendon, Massachusetts, USA
- GAMA Therapeutics LLC, Pepperell, Massachusetts, USA
| | - Emmanouil Magiorkinis
- Department of Hygiene, Epidemiology and Medical Statistics, Medical School, University of Athens, Athens-Goudi, Greece
| | | | - Michael R Hamblin
- Harvard-MIT Division of Health Science and Technology, Cambridge, Massachusetts, USA
- Department of Dermatology, Harvard Medical School, Boston, Massachusetts, USA
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Maria Hadjifrangiskou
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - George P Tegos
- Gliese 623b, Mendon, Massachusetts, USA
- GAMA Therapeutics LLC, Pepperell, Massachusetts, USA
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Yılmaz EŞ, Çetin SK, Duran N. Diyabetik ayak yaralarında nadir bir etmen: Corynebacterium striatum. CUKUROVA MEDICAL JOURNAL 2018. [DOI: 10.17826/cumj.350084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
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Sung JY. Molecular Characterization and Antimicrobial Susceptibility of Biofilm-forming Acinetobacter baumannii Clinical Isolates from Daejeon, Korea. KOREAN JOURNAL OF CLINICAL LABORATORY SCIENCE 2018. [DOI: 10.15324/kjcls.2018.50.2.100] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Affiliation(s)
- Ji Youn Sung
- Department of Biomedical Laboratory Science, Far East University, Eumseong, Korea
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Phenotypic and Genotypic Investigation of Biofilm Formation in Clinical and Environmental Isolates of Acinetobacter baumannii. ARCHIVES OF CLINICAL INFECTIOUS DISEASES 2018. [DOI: 10.5812/archcid.12914] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Karumathil DP, Nair MS, Gaffney J, Kollanoor-Johny A, Venkitanarayanan K. Trans-Cinnamaldehyde and Eugenol Increase Acinetobacter baumannii Sensitivity to Beta-Lactam Antibiotics. Front Microbiol 2018; 9:1011. [PMID: 29875743 PMCID: PMC5974060 DOI: 10.3389/fmicb.2018.01011] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2017] [Accepted: 04/30/2018] [Indexed: 01/23/2023] Open
Abstract
Multi-drug resistant (MDR) Acinetobacter baumannii is a major nosocomial pathogen causing a wide range of clinical conditions with significant mortality rates. A. baumannii strains are equipped with a multitude of antibiotic resistance mechanisms, rendering them resistant to most of the currently available antibiotics. Thus, there is a critical need to explore novel strategies for controlling antibiotic resistance in A. baumannii. This study investigated the efficacy of two food-grade, plant-derived antimicrobials (PDAs), namely trans-cinnamaldehyde (TC) and eugenol (EG) in decreasing A. baumannii’s resistance to seven β-lactam antibiotics, including ampicillin, methicillin, meropenem, penicillin, aztreonam, amoxicillin, and piperacillin. Two MDR A. baumannii isolates (ATCC 17978 and AB 251847) were separately cultured in tryptic soy broth (∼6 log CFU/ml) containing the minimum inhibitory concentration (MIC) of TC or EG with or without the MIC of each antibiotic at 37°C for 18 h. A. baumannii strains not exposed to the PDAs or antibiotics served as controls. Following incubation, A. baumannii counts were determined by broth dilution assay. In addition, the effect of PDAs on the permeability of outer membrane and efflux pumps in A. baumannii was measured. Further, the effect of TC and EG on the expression of A. baumannii genes encoding resistance to β-lactam antibiotics (blaP), efflux pumps (adeABC), and multi-drug resistant protein (mdrp) was studied using real-time quantitative PCR (RT-qPCR). The experiment was replicated three times with duplicate samples of each treatment and control. The results from broth dilution assay indicated that both TC and EG in combination with antibiotics increased the sensitivity of A. baumannii to all the tested antibiotics (P < 0.05). The two PDAs inhibited the function of A. baumannii efflux pump, (AdeABC), but did not increase the permeability of its outer membrane. Moreover, RT-qPCR data revealed that TC and EG down-regulated the expression of majority of the genes associated with β-lactam antibiotic resistance, especially blaP and adeABC (P < 0.05). The results suggest that TC and EG could potentially be used along with β-lactam antibiotics for controlling MDR A. baumannii infections; however, their clinical significance needs to be determined using in vivo studies.
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Affiliation(s)
- Deepti P Karumathil
- Department of Animal Science, University of Connecticut, Storrs, CT, United States
| | - Meera Surendran Nair
- Department of Animal Science, University of Connecticut, Storrs, CT, United States
| | - James Gaffney
- College of Veterinary Medicine, Cornell University, Ithaca, NY, United States
| | - Anup Kollanoor-Johny
- Department of Animal Science, University of Minnesota, Saint Paul, MN, United States
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Vatan A, Saltoglu N, Yemisen M, Balkan II, Surme S, Demiray T, Mete B, Tabak F. Association between biofilm and multi/extensive drug resistance in diabetic foot infection. Int J Clin Pract 2018; 72:e13060. [PMID: 29381248 DOI: 10.1111/ijcp.13060] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2017] [Accepted: 12/22/2017] [Indexed: 12/23/2022] Open
Abstract
PURPOSE We aimed to determine significant risk factors for biofilm production and to investigate the association between antimicrobial resistance profile and biofilm formation in the bacterial isolates obtained from patients with diabetic foot infection (DFI). METHODS Demographic, clinical, laboratory and outcome data of 165 patients, prospectively recorded and followed between January 2008 and December 2015 by a multidisciplinary committee, were analysed. Standard microbiological methods were adopted. Risk factors associated with biofilm were determined by univariate and multivariate analyses. RESULTS The overall rate of biofilm production among 339 wound isolates was 34%. The biofilm production rate was significantly higher in Gram-negative micro-organisms (39%) in comparison with Gram positives (21%) (P = .01). A. baumannii presented the highest biofilm production (62%), followed by P. aeruginosa (52%) and Klebsiella spp. (40%). On univariate analysis, significant factors associated with biofilm were antibiotic use within last 3 months (OR:2.94, CI: 1.5-5.75, P = .002), recurrent DFI within last 6 months (OR:2.35, CI: 1.23-4.53, P = .01), hospitalisation within last 3 months due to ipsilateral recurrent DFI (OR:2.44, CI: 1.06-5.58, P = .03), presence of amputation history (OR: 2.20, CI: 1.14-4.24, P = .01), multidrug-resistant (MDR) micro-organism (OR: 7.76, CI: 4.53-13.35, P<.001) and extensively drug-resistant (XDR) micro-organism (OR:11.33, CI:4.97-26.55, P<.001). Multivariate regression analysis revealed two variables to be significant factors associated with biofilm: MDR micro-organism (OR: 3.63, CI: 1.58-8.33, P = .002) and XDR micro-organism (OR:4.06, CI: 1.25-13.1, P = .01). CONCLUSIONS Multi/extensive drug resistance and previous recurrent DFIs were significantly associated with biofilm formation in patients with diabetic foot.
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Affiliation(s)
- Aslı Vatan
- Cerrahpasa Medical Faculty, Infectious Diseases and Clinical Microbiology, Istanbul University, Istanbul, Turkey
| | - Nese Saltoglu
- Cerrahpasa Medical Faculty, Infectious Diseases and Clinical Microbiology, Istanbul University, Istanbul, Turkey
| | - Mucahit Yemisen
- Cerrahpasa Medical Faculty, Infectious Diseases and Clinical Microbiology, Istanbul University, Istanbul, Turkey
| | - Ilker Inanc Balkan
- Cerrahpasa Medical Faculty, Infectious Diseases and Clinical Microbiology, Istanbul University, Istanbul, Turkey
| | - Serkan Surme
- Cerrahpasa Medical Faculty, Infectious Diseases and Clinical Microbiology, Istanbul University, Istanbul, Turkey
| | - Tayfur Demiray
- Sakarya University Medical Faculty, Microbiology, Sakarya, Turkey
| | - Birgul Mete
- Cerrahpasa Medical Faculty, Infectious Diseases and Clinical Microbiology, Istanbul University, Istanbul, Turkey
| | - Fehmi Tabak
- Cerrahpasa Medical Faculty, Infectious Diseases and Clinical Microbiology, Istanbul University, Istanbul, Turkey
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Bogdan M, Drenjancevic D, Harsanji Drenjancevic I, Bedenic B, Zujic Atalic V, Talapko J, Vukovic D. In vitro effect of subminimal inhibitory concentrations of antibiotics on the biofilm formation ability of Acinetobacter baumannii clinical isolates. J Chemother 2017; 30:16-24. [PMID: 28956494 DOI: 10.1080/1120009x.2017.1378835] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
The ability of A cinetobacter baumannii strains to form biofilm is one of the most important virulence factor which enables bacterial survival in a harsh environment and decreases antibiotic concentration as well. Subminimal inhibitory concentrations (subMICs) of antibiotics may change bacterial ultrastructure or have an influence on some different molecular mechanisms resulting in morphological or physiological changes in bacteria itself. The aim of this study was to determine effects of 1/2, 1/4, 1/8 and 1/16 minimal inhibitory concentrationsof imipenem, ampicillin-sulbactam, azithromycin, rifampicin and colistin on biofilm formation ability of 22 biofilm non-producing and 46 biofilm producing A. baumannii strains (30 weak producing strains and 16 moderate producing strains). Results of this study indicate that 1/2-1/16 MICs of imipenem, azithromycin, and rifampicin can reduce bacterial biofilm formation ability in moderate producing strains (p < 0.05), whereas 1/16 MIC of imipenem and 1/4-1/8 MICs of rifampicin reduce the biofilm formation in weak producing strains (p < 0.05). Statisticaly significant effect was detected among biofilm non-producing strains after their exposure to 1/16 MIC of azithromycin (p = 0.039). SubMICs of ampicillin-sulbactam and colistin did not have any significant effect on biofilm formation among tested A. baumannii strains.
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Affiliation(s)
- Maja Bogdan
- a Microbiology Service , Institute of Public Health Osijek-Baranja County , Osijek , Croatia.,b Faculty of Medicine, Department of Microbiology and Parasitology , University of Osijek , Osijek , Croatia
| | - Domagoj Drenjancevic
- b Faculty of Medicine, Department of Microbiology and Parasitology , University of Osijek , Osijek , Croatia.,c Department of Transfusion Medicine , Osijek University Hospital , Osijek , Croatia
| | - Ivana Harsanji Drenjancevic
- d Department of Anesthesiology, Reanimatology and Intensive Medicine , Osijek University Hospital , Osijek , Croatia.,e Faculty of Medicine, Department of Anesthesiology, Reanimatology and Intensive Medicine , University of Osijek , Osijek , Croatia
| | - Branka Bedenic
- f Department of Clinical and Molecular Microbiology , University Hospital Center Zagreb , Zagreb , Croatia.,g Department of Microbiology and Parasitology , School of Medicine, University of Zagreb , Zagreb , Croatia
| | - Vlasta Zujic Atalic
- a Microbiology Service , Institute of Public Health Osijek-Baranja County , Osijek , Croatia.,b Faculty of Medicine, Department of Microbiology and Parasitology , University of Osijek , Osijek , Croatia
| | - Jasminka Talapko
- b Faculty of Medicine, Department of Microbiology and Parasitology , University of Osijek , Osijek , Croatia
| | - Dubravka Vukovic
- a Microbiology Service , Institute of Public Health Osijek-Baranja County , Osijek , Croatia
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Krzyściak P, Chmielarczyk A, Pobiega M, Romaniszyn D, Wójkowska-Mach J. Acinetobacter baumannii isolated from hospital-acquired infection: biofilm production and drug susceptibility. APMIS 2017; 125:1017-1026. [PMID: 28913903 DOI: 10.1111/apm.12739] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2016] [Accepted: 06/06/2017] [Indexed: 01/03/2023]
Abstract
Acinetobacter baumannii cause opportunistic nosocomial infections and is often multidrug resistant. It has ability to form biofilm. The possession of drug resistance mechanism and ability of biofilm formation seems to be the different way to enhancement of viability in stressful environment. In this study, we evaluate relation between these two factors. The biofilm formation was investigated in M63 medium with casein in microtiter plates, and the drug susceptibility was performed by disk diffusion methods. We found that 80-98% strains formed a biofilm. Strains showing sensitivity to amikacin and tobramycin from ICU produced more biofilm than strains showing resistance to these antibiotics. Ceftazidime-sensitive strains formed a smaller biofilm than resistant. The logistic regression shows association between drug resistance and strains originating from ICU. In case of ceftazidime, strong biofilm formation and descending from ICU reduced the likelihood of drug sensitivity. For other drugs such as aminoglycosides, fluoroquinolones, trimethoprim/sulfamethoxazole, and tetracycline, we found opposite relation (but it was not statistically significance). However, generally it seems that strong biofilm producers from ICUs are often more susceptible to antibiotics. This situation can be explained by the fact that bacteria protected in biofilm do not need mechanisms responsible for resistance of planktonic cells.
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Affiliation(s)
- Paweł Krzyściak
- Department of Mycology, Jagiellonian University Medical College, Krakow, Poland
| | - Agnieszka Chmielarczyk
- Department of Bacteriology, Microbial Ecology and Parasitology, Jagiellonian University Medical College, Krakow, Poland
| | - Monika Pobiega
- Department of Bacteriology, Microbial Ecology and Parasitology, Jagiellonian University Medical College, Krakow, Poland
| | - Dorota Romaniszyn
- Department of Bacteriology, Microbial Ecology and Parasitology, Jagiellonian University Medical College, Krakow, Poland
| | - Jadwiga Wójkowska-Mach
- Department of Bacteriology, Microbial Ecology and Parasitology, Jagiellonian University Medical College, Krakow, Poland
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Rosales-Reyes R, Gayosso-Vázquez C, Fernández-Vázquez JL, Jarillo-Quijada MD, Rivera-Benítez C, Santos-Preciado JI, Alcántar-Curiel MD. Virulence profiles and innate immune responses against highly lethal, multidrug-resistant nosocomial isolates of Acinetobacter baumannii from a tertiary care hospital in Mexico. PLoS One 2017; 12:e0182899. [PMID: 28797068 PMCID: PMC5552319 DOI: 10.1371/journal.pone.0182899] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2017] [Accepted: 07/26/2017] [Indexed: 11/18/2022] Open
Abstract
Virulence profiles and innate immune responses were studied in Acinetobacter baumannii from nosocomial infections collected over one year in a tertiary care hospital in Mexico. A. baumannii were identified by VITEK 2 System followed by susceptibility tests. Carbapenemase genes, active efflux mechanism to imipenem and meropenem and outer membrane proteins profile were analyzed to evaluate their role on the activity of carbapenem resistance. All isolates were genotyped by pulsed field gel electrophoresis. The ability to form biofilm was determined on a polystyrene surface. The resistance to complement was determined with a pooled human normal serum and TNFα release by infected macrophages was determined by ELISA. The 112 isolates from this study were associated with a 52% of mortality. All were resistance to β-lactams, fluoroquinolones, and trimethroprim-sulfamethoxal, 96 and 90% were resistant to meropenem and imipenem, respectively, but with high susceptibility to polymyxin B, colistin and tigecyclin. Isolates were classified in 11 different clones. Most isolates, 88% (99/112), were metallo-β-lactamases and carbapenemases producers, associated in 95% with the presence of blaOXA-72 gene. Only 4/99 and 1/99 of the carbapenem-resistant isolates were related to efflux mechanism to meropenem or imipenem resistance, respectively. The loss of expression of 22, 29, and/or 33-36-kDa proteins was detected in 8/11 of the clinical isolates with resistance to carbapenem. More than 96% (108/112) of the isolates were high producers of biofilms on biotic surfaces. Finally, all isolates showed variable resistance to normal human serum activity and were high inductors of TNFα release by macrophages. In summary, these results suggest that multidrug-resistant A. baumannii can persist in the hospital environment through its ability to form biofilms. The high mortality observed was due to their ability to survive normal human serum activity and capability to induce potent inflammatory immune response making this nosocomial pathogen a serious threat to hospitalized patients.
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Affiliation(s)
- Roberto Rosales-Reyes
- Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México. Ciudad de México, México
- * E-mail: (MDAC); (RRR)
| | - Catalina Gayosso-Vázquez
- Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México. Ciudad de México, México
| | - José Luis Fernández-Vázquez
- Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México. Ciudad de México, México
| | - Ma Dolores Jarillo-Quijada
- Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México. Ciudad de México, México
| | | | - José Ignacio Santos-Preciado
- Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México. Ciudad de México, México
| | - María Dolores Alcántar-Curiel
- Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México. Ciudad de México, México
- * E-mail: (MDAC); (RRR)
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Chen R, Lv R, Xiao L, Wang M, Du Z, Tan Y, Cui Y, Yan Y, Luo Y, Yang R, Song Y. A1S_2811, a CheA/Y-like hybrid two-component regulator from Acinetobacter baumannii ATCC17978, is involved in surface motility and biofilm formation in this bacterium. Microbiologyopen 2017; 6. [PMID: 28714256 PMCID: PMC5635159 DOI: 10.1002/mbo3.510] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2017] [Revised: 05/22/2017] [Accepted: 05/25/2017] [Indexed: 12/14/2022] Open
Abstract
Two‐component systems in Acinetobacter baumannii are associated with its virulence, drug resistance, motility, biofilm formation, and other characteristics. In this study, we used RecAb, a genetic engineering method, to investigate the function of A1S_2811 in A. baumannii strain ATCC17978. A1S_2811, a hypothetical hybrid sensor histidine kinase/response regulator, has four histidine‐containing phosphotransfer domains, a CheA‐like regulatory domain, and a CheY‐like receiver domain at its C terminus. Compared with the ATCC17978 strain, both surface motility and biofilm formation at the gas–liquid interface decreased significantly in the A1S_2811 knock‐out strain. The number of pilus‐like structures and the amount of extrapolymeric substances on the cell surface also decreased in the A1S_2811 null strain. Transcription of abaI, which encodes an N‐acylhomoserine lactone synthase in A. baumannii , decreased significantly in the A1S_2811 null strain, and supplementation with synthetic N‐(3‐oxodecanoyl) homoserine‐l‐lactone rescued the surface motility and biofilm formation phenotype in the null mutant. We speculate that A1S_2811 regulates surface motility and biofilm formation, not by regulating type IV pili‐associated genes expression, but by regulating the chaperone/usher pili‐associated csuA/ABCDE operon and the AbaI‐dependent quorum‐sensing pathway‐associated A1S_0112‐0119 operon instead.
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Affiliation(s)
- Rong Chen
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.,Department of Clinical Microbiology, General Hospital of Chinese People's Liberation Army, Beijing, China
| | - Ruichen Lv
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China
| | - Lisheng Xiao
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China
| | - Min Wang
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China
| | - Zongmin Du
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China
| | - Yafang Tan
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China
| | - Yujun Cui
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China
| | - Yanfeng Yan
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China
| | - Yanping Luo
- Department of Clinical Microbiology, General Hospital of Chinese People's Liberation Army, Beijing, China
| | - Ruifu Yang
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China
| | - Yajun Song
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China
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Bardoloi V, Yogeesha Babu KV. Comparative study of isolates from community-acquired and catheter-associated urinary tract infections with reference to biofilm-producing property, antibiotic sensitivity and multi-drug resistance. J Med Microbiol 2017; 66:927-936. [PMID: 28703700 DOI: 10.1099/jmm.0.000525] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
PURPOSE Urinary tract infection (UTI) can be community-acquired (Com-UTI) or catheter-associated (CAUTI) and may be associated with biofilm-producing organisms. A comparative analysis of biofilm-producing property (BPP), antibiotic-sensitivity and multi-drug resistance (MDR) and their relation with the BPP of isolates from Com-UTI and CAUTI has not yet been performed and necessitated this study. METHODOLOGY OBJECTIVES (1) isolation of bacteria from CAUTI and Com-UTI and identification of their BPP, antibiotic-sensitivity and MDR status; (2) comparison of the isolates from CAUTI and Com-UTI as regards BPP, MDR status and their relation with BPP. METHOD isolates from 100 cases each of Com-UTI and CAUTI were subjected to Congo redagar (CRA) and Safranin tube tests. Antibiotic susceptibility was investigated using the disc diffusion method. Both groups were compared regarding BPP, drug sensitivity and MDR status. Statistical analyses were performed using χ2 and Fisher's exact tests. RESULTS 76.19 % of isolates from Com-UTI and 60.72 % from CAUTI had BPP (P=0.0252; significant). The Safranin tube test detected more isolates with BPP than the CRA test. MDR is greater in CAUTI than Com-UTI (83.33 % versus 64.76 %; P=0.0039; significant). MDR is greater in isolates with BPP in both Com-UTI and CAUTI (76.47 and 62.35 %; non-significant). CONCLUSIONS BPP was found in both Com-UTI and CAUTI. When used together, the Safranin tube test and the CRA test increased the sensitivity of detecting BPP. MDR was higher in CAUTI than Com-UTI. MDR and BPP are not interrelated or associated, especially in settings where it is not certain that isolates were obtained from a well-formed biofilm. However, this does not rule out a higher incidence or prevalence of MDR in isolates with BPP taken directly from the biofilms.
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Affiliation(s)
- Vishwajeet Bardoloi
- Department of Microbiology, Azeezia Institute of Medical Sciences and Research, Kollam, Kerala, India
| | - K V Yogeesha Babu
- Department of Microbiology, Azeezia Institute of Medical Sciences and Research, Kollam, Kerala, India
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Acinetobacter sp. DW-1 immobilized on polyhedron hollow polypropylene balls and analysis of transcriptome and proteome of the bacterium during phenol biodegradation process. Sci Rep 2017; 7:4863. [PMID: 28687728 PMCID: PMC5501837 DOI: 10.1038/s41598-017-04187-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2016] [Accepted: 05/03/2017] [Indexed: 02/07/2023] Open
Abstract
Phenol is a hazardous chemical known to be widely distributed in aquatic environments. Biodegradation is an attractive option for removal of phenol from water sources. Acinetobacter sp. DW-1 isolated from drinking water biofilters can use phenol as a sole carbon and energy source. In this study, we found that Immobilized Acinetobacter sp. DW-1cells were effective in biodegradation of phenol. In addition, we performed proteome and transcriptome analysis of Acinetobacter sp. DW-1 during phenol biodegradation. The results showed that Acinetobacter sp. DW-1 degrades phenol mainly by the ortho pathway because of the induction of phenol hydroxylase, catechol-1,2-dioxygenase. Furthermore, some novel candidate proteins (OsmC-like family protein, MetA-pathway of phenol degradation family protein, fimbrial protein and coenzyme F390 synthetase) and transcriptional regulators (GntR/LuxR/CRP/FNR/TetR/Fis family transcriptional regulator) were successfully identified to be potentially involved in phenol biodegradation. In particular, MetA-pathway of phenol degradation family protein and fimbrial protein showed a strong positive correlation with phenol biodegradation, and Fis family transcriptional regulator is likely to exert its effect as activators of gene expression. This study provides valuable clues for identifying global proteins and genes involved in phenol biodegradation and provides a fundamental platform for further studies to reveal the phenol degradation mechanism of Acinetobacter sp.
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Mohammadi M, Soroush S, Delfani S, Pakzad I, Abbaszadeh A, Bahmani M, Bogdanovic L, Taherikalani M. Distribution of Class D Carbapenemase and Extended-Spectrum β-Lactamase Genes among Acinetobacter Baumannii Isolated from Burn Wound and Ventilator Associated Pneumonia Infections. J Clin Diagn Res 2017; 11:DC19-DC23. [PMID: 28892891 DOI: 10.7860/jcdr/2017/25534.10218] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2016] [Accepted: 04/10/2017] [Indexed: 12/27/2022]
Abstract
INTRODUCTION Resistance to Acinetobacter baumannii is dramatically on the rise in Iran. Therefore, it is important to study resistance pattern among Acinetobacter isolates which is a common cause of nosocomial infections. AIM To investigate antibiotic resistance patterns and the role of resistant genes and biofilm formation in the induction of resistance among Acinetobacter baumannii isolated from burn wound and ventilator associated pneumonia infections. MATERIALS AND METHODS Total 103 isolates such as 33 burn samples from Rasool Akram Hospital and 70 isolates from ventilated patients in Shahid Motahhari Hospital were identified with A. baumannii using biochemical method, and then identified to species level with PCR of gyrB and blaOXA-51 gene. Antibiotic sensitivity pattern for β-lactam and carbapenem antibiotics was assessed using Agar disc diffusion test and E-test. The presence of different carbapenemase and metalo-β-lactamase (blaOXA-51-like, gyrB, blaOXA-23-like, blaOXA-24-like, blaOXA-58, blaVEB, blaPER, blaGIM, blaSIM, blaIMP, blaVIM), extended-spectrum β-lactamases (blaTEM, blaSHV) and two insertion sequences genes (ISaba1, IS1113) was assessed. Biofilm formation of all isolates was then assessed. Chi-square analysis or Fisher's-exact tests were used for statistical analysis. A p-value <0.05 was considered statistically significant. RESULTS Colistin was the most effective antimicrobial agents, although 10.7% (11/103) of the isolates were resistant. The high rate of resistance to meropenem (93.2%) and imipenem (90.3%) was determined. Also, with exception of ampicillin-sulbactam, surprisingly the resistant rate was 28.2%, the resistance to β-lactam antibiotic was dramatically increased. Co-existence of two and three blaOXA genes was also determined. The blaOXA-58 was detected in only one isolate. The blaTEM and blaOXA-23 was the most prevalent Extended-Spectrum β-Lactamases (ESBL) gene. All isolates were biofilm producers. CONCLUSION Antibiotic resistance is increasing among A. baumannii isolates which is due to excessive use of antibiotics and also acquired resistant genes and biofilm production. Resistance to nearly all antimicrobial agents especially colistin as end choice for treatment of multiple drug resistance A. baumannii is a big concern.
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Affiliation(s)
- Maryam Mohammadi
- Clinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran
| | - Setareh Soroush
- Razi Herbal Medicines Research Center, Department of Microbiology, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Somayeh Delfani
- Razi Herbal Medicines Research Center, Department of Microbiology, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Iraj Pakzad
- Clinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran
| | - Abolfazl Abbaszadeh
- Department of Surgery, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Mahmoud Bahmani
- Biotechnology and Medicinal Plants Research Center, Ilam University of Medical Sciences, Ilam Iran
| | - Lidija Bogdanovic
- Department of Public Health, University of Naples Federico II, Naples, Italy
| | - Morovat Taherikalani
- Razi Herbal Medicines Research Center, Department of Microbiology, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
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Chiang SR, Jung F, Tang HJ, Chen CH, Chen CC, Chou HY, Chuang YC. Desiccation and ethanol resistances of multidrug resistant Acinetobacter baumannii embedded in biofilm: The favorable antiseptic efficacy of combination chlorhexidine gluconate and ethanol. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2017; 51:770-777. [PMID: 28732564 DOI: 10.1016/j.jmii.2017.02.003] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/05/2016] [Revised: 01/04/2017] [Accepted: 02/21/2017] [Indexed: 01/09/2023]
Abstract
BACKGROUND/PURPOSE Globally, multidrug-resistant Acinetobacter baumannii (MDRAB) has emerged as an important pathogen in nosocomial outbreaks. This study aimed to investigate the correlation between the biofilm formation and survival of MDRABs, and to investigate the antiseptic efficacy of hand sanitizers for the MDRABs, embedded with biofilm (MDRAB-Bs). METHODS The MDRABs were selected randomly after pulsed-field gel electrophoresis (PFGE), and their biofilm formation was analyzed. Desiccation and ethanol tolerances were assayed to test the bacterial survival. The antiseptic efficacy of combined chlorhexidine gluconate (CHG) and 70% ethanol agents against MDRAB-Bs were compared with the 70% ethanol cleanser. RESULTS Eleven MDRABs, which varied in biofilm formation (MRDAB-B) and planktonic type (MDRAB-P), were tested. In desiccation survival, the mean survival time for the MDRAB-Bs was 49.0 days which was significantly higher than that of their planktonic type (17.3 days) (P < 0.005). The MDRAB-Ps could be eliminated after a 10 min contact with a 30% ethanol agent, however, it took 10 min of 70% ethanol to eliminate the MDRAB-Bs. On the other hand, a 2% CHG in 70% ethanol solution completely eliminated all MDRAB-Bs after 1 min contacted time. The 2% CHG in 70% ethanol agent provided a significantly superior efficacy than the 70% ethanol solution at eliminating the MDRAB-Bs (P < 0.005). CONCLUSION MDRAB with biofilm-formation presented significantly higher desiccation and ethanol resistances than their planktonic type. Moreover, the 2% CHG in 70% ethanol agent provided a superior antiseptic efficacy for MDRAB-Bs than that of the 70% ethanol agent.
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Affiliation(s)
- Shyh-Ren Chiang
- Department of Internal Medicine, Chi Mei Medical Center, Tainan City, Taiwan; Chia Nan University of Pharmacy & Science, Tainan City, Taiwan.
| | - Fang Jung
- Department of Respiratory Therapy, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
| | - Hung-Jen Tang
- Department of Internal Medicine, Chi Mei Medical Center, Tainan City, Taiwan; Chia Nan University of Pharmacy & Science, Tainan City, Taiwan.
| | - Chung-Hua Chen
- Department of Medicine, En Chu Kong Hospital, Taipei County, Taiwan.
| | - Chi-Chung Chen
- Department of Medical Research, Chi Mei Medical Center, Tainan City, Taiwan; Institute of Biotechnology, National Cheng Kung University, Tainan City, Taiwan.
| | - Hsiu-Yin Chou
- Department of Pathology, Chi Mei Medical Center, Tainan City, Taiwan.
| | - Yin-Ching Chuang
- Department of Medical Research, Chi Mei Medical Center, Tainan City, Taiwan; Department of Medicine, Chi Mei Medical Center-Liou Ying, Tainan City, Taiwan.
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Biofilm is a Major Virulence Determinant in Bacterial Colonization of Chronic Skin Ulcers Independently from the Multidrug Resistant Phenotype. Int J Mol Sci 2017; 18:ijms18051077. [PMID: 28513576 PMCID: PMC5454986 DOI: 10.3390/ijms18051077] [Citation(s) in RCA: 71] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2017] [Revised: 05/06/2017] [Accepted: 05/11/2017] [Indexed: 01/28/2023] Open
Abstract
Bacterial biofilm is a major factor in delayed wound healing and high levels of biofilm production have been repeatedly described in multidrug resistant organisms (MDROs). Nevertheless, a quantitative correlation between biofilm production and the profile of antimicrobial drug resistance in delayed wound healing remains to be determined. Microbial identification, antibiotic susceptibility and biofilm production were assessed in 135 clinical isolates from 87 patients. Gram-negative bacteria were the most represented microorganisms (60.8%) with MDROs accounting for 31.8% of the total isolates. Assessment of biofilm production revealed that 80% of the strains were able to form biofilm. A comparable level of biofilm production was found with both MDRO and not-MDRO with no significant differences between groups. All the methicillin-resistant Staphylococcus aureus (MRSA) and 80% of Pseudomonas aeruginosa MDR strains were found as moderate/high biofilm producers. Conversely, less than 17% of Klebsiella pneumoniae extended-spectrum beta-lactamase (ESBL), Escherichia coli-ESBL and Acinetobacter baumannii were moderate/high biofilm producers. Notably, those strains classified as non-biofilm producers, were always associated with biofilm producer bacteria in polymicrobial colonization. This study shows that biofilm producers were present in all chronic skin ulcers, suggesting that biofilm represents a key virulence determinant in promoting bacterial persistence and chronicity of ulcerative lesions independently from the MDRO phenotype.
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Bardbari AM, Arabestani MR, Karami M, Keramat F, Alikhani MY, Bagheri KP. Correlation between ability of biofilm formation with their responsible genes and MDR patterns in clinical and environmental Acinetobacter baumannii isolates. Microb Pathog 2017; 108:122-128. [PMID: 28457900 DOI: 10.1016/j.micpath.2017.04.039] [Citation(s) in RCA: 77] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2017] [Revised: 04/26/2017] [Accepted: 04/26/2017] [Indexed: 10/19/2022]
Abstract
Acinetobacter baumannii potential to form biofilm and exhibit multiple antibiotic resistances may be responsible in its survival in hospital environment. Accordingly, our study was aimed to determine the correlation between ability of biofilm formation and the frequency of biofilm related genes with antibiotic resistance phenotypes, and also the categorization of their patterns in clinical and environmental isolates. A total of 75 clinical and 32 environmental strains of the A. baumannii were collected and identified via API 20NE. Antibiotic susceptibility was evaluated by disk diffusion and microdilution broth methods. Biofilm formation assay was performed by microtiter plate method. OXA types and biofilm related genes including BlaOXA-51, BlaOXA-23, BlaOXA-24, BlaOXA-58, bap, blaPER-1, and ompA were amplified by PCR. The rate of MDR A. baumannii in clinical isolates (100%) was higher than environmental (81.2%) isolates (p < 0.05). Among 10 antibiotypes, the predominant resistance pattern in clinical and environmental isolates was antibiotypes I (85.3 and 78.1%, respectively). Analysis of the frequency of blaOXA-23 gene revealed a statistically significant difference between clinical (85.3%) and environmental (68.7%) isolates (p < 0.05). The prevalence of strong biofilm producers in clinical and environmental isolates were 31.2%-58.7%, respectively. In the clinical and environmental isolates, the frequencies of ompA, blaRER-1 and bap genes were 100%, 53.3%, 82.7% and 100%, 37.5%, 84.4% respectively. Statistical analysis revealed a significant correlation between the frequency of MDR isolates and biofilm formation ability (p = 0.008). The high frequency of antibiotype I would be indicated that an outbreak has been happened earlier and an endemic strain is currently being settled in the hospital environment. It would be suggested that if there was no difference in the frequency of pattern I and biofilm formation ability between clinical and environmental isolates, it is a critical point representing the higher risk of bacterial transmission from environment to the patients. The resulting data would be assisted in the improvement of disinfection strategies to better control of nosocomial infections. One dominant resistance pattern has shown among clinical and environmental isolates. The frequency of blaOXA-23 had significant difference between clinical and environmental isolates. The presence of bap gene in the A. baumannii isolates was associated with biofilm formation. There was a significant correlation between multiple drug resistance and biofilm formation. The clinical isolates had a higher ability to form strong biofilms compared to the environmental samples.
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Affiliation(s)
- Ali Mohammadi Bardbari
- Department of Microbiology, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
| | - Mohammad Reza Arabestani
- Department of Microbiology, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
| | - Manoochehr Karami
- Department of Epidemiology, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran.
| | - Fariba Keramat
- Department of Infectious Diseases, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran; Brucellosis Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
| | - Mohammad Yousef Alikhani
- Department of Microbiology, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran; Brucellosis Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
| | - Kamran Pooshang Bagheri
- Venom and Biotherapeutics Molecules Lab., Medical Biotechnology Dept., Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
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Saranathan R, Pagal S, Sawant AR, Tomar A, Madhangi M, Sah S, Satti A, Arunkumar KP, Prashanth K. Disruption of tetR type regulator adeN by mobile genetic element confers elevated virulence in Acinetobacter baumannii. Virulence 2017; 8:1316-1334. [PMID: 28436748 DOI: 10.1080/21505594.2017.1322240] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
Acinetobacter baumannii is an important human pathogen and considered as a major threat due to its extreme drug resistance. In this study, the genome of a hyper-virulent MDR strain PKAB07 of A. baumannii isolated from an Indian patient was sequenced and analyzed to understand its mechanisms of virulence, resistance and evolution. Comparative genome analysis of PKAB07 revealed virulence and resistance related genes scattered throughout the genome, instead of being organized as an island, indicating the highly mosaic nature of the genome. Many intermittent horizontal gene transfer events, insertion sequence (IS) element insertions identified were augmenting resistance machinery and elevating the SNP densities in A. baumannii eventually aiding in their swift evolution. ISAba1, the most widely distributed insertion sequence in A. baumannii was found in multiple sites in PKAB07. Out of many ISAba1 insertions, we identified novel insertions in 9 different genes wherein insertional inactivation of adeN (tetR type regulator) was significant. To assess the significance of this disruption in A. baumannii, adeN mutant and complement strains were constructed in A. baumannii ATCC 17978 strain and studied. Biofilm levels were abrogated in the adeN knockout when compared with the wild type and complemented strain of adeN knockout. Virulence of the adeN knockout mutant strain was observed to be high, which was validated by in vitro experiments and Galleria mellonella infection model. The overexpression of adeJ, a major component of AdeIJK efflux pump observed in adeN knockout strain could be the possible reason for the elevated virulence in adeN mutant and PKB07 strain. Knocking out of adeN in ATCC strain led to increased resistance and virulence at par with the PKAB07. Disruption of tetR type regulator adeN by ISAba1 consequently has led to elevated virulence in this pathogen.
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Affiliation(s)
- Rajagopalan Saranathan
- a Department of Biotechnology, School of Life Sciences , Pondicherry University , Puducherry , India
| | - Sudhakar Pagal
- a Department of Biotechnology, School of Life Sciences , Pondicherry University , Puducherry , India
| | - Ajit R Sawant
- a Department of Biotechnology, School of Life Sciences , Pondicherry University , Puducherry , India
| | - Archana Tomar
- b Laboratory of Molecular Genetics , Centre for DNA Fingerprinting and Diagnostics (CDFD) , Hyderabad , India
| | - M Madhangi
- a Department of Biotechnology, School of Life Sciences , Pondicherry University , Puducherry , India
| | - Suresh Sah
- a Department of Biotechnology, School of Life Sciences , Pondicherry University , Puducherry , India
| | - Annapurna Satti
- b Laboratory of Molecular Genetics , Centre for DNA Fingerprinting and Diagnostics (CDFD) , Hyderabad , India
| | - K P Arunkumar
- b Laboratory of Molecular Genetics , Centre for DNA Fingerprinting and Diagnostics (CDFD) , Hyderabad , India
| | - K Prashanth
- a Department of Biotechnology, School of Life Sciences , Pondicherry University , Puducherry , India
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Antibiotic Resistance Determinant-Focused Acinetobacter baumannii Vaccine Designed Using Reverse Vaccinology. Int J Mol Sci 2017; 18:ijms18020458. [PMID: 28230771 PMCID: PMC5343991 DOI: 10.3390/ijms18020458] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2016] [Revised: 01/31/2017] [Accepted: 02/10/2017] [Indexed: 12/11/2022] Open
Abstract
As one of the most influential and troublesome human pathogens, Acinetobacter baumannii (A. baumannii) has emerged with many multidrug-resistant strains. After collecting 33 complete A. baumannii genomes and 84 representative antibiotic resistance determinants, we used the Vaxign reverse vaccinology approach to predict classical type vaccine candidates against A. baumannii infections and new type vaccine candidates against antibiotic resistance. Our genome analysis identified 35 outer membrane or extracellular adhesins that are conserved among all 33 genomes, have no human protein homology, and have less than 2 transmembrane helices. These 35 antigens include 11 TonB dependent receptors, 8 porins, 7 efflux pump proteins, and 2 fimbrial proteins (FilF and CAM87009.1). CAM86003.1 was predicted to be an adhesin outer membrane protein absent from 3 antibiotic-sensitive strains and conserved in 21 antibiotic-resistant strains. Feasible anti-resistance vaccine candidates also include one extracellular protein (QnrA), 3 RND type outer membrane efflux pump proteins, and 3 CTX-M type β-lactamases. Among 39 β-lactamases, A. baumannii CTX-M-2, -5, and -43 enzymes are predicted as adhesins and better vaccine candidates than other β-lactamases to induce preventive immunity and enhance antibiotic treatments. This report represents the first reverse vaccinology study to systematically predict vaccine antigen candidates against antibiotic resistance for a microbial pathogen.
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Granov D, Ljubovic AD, Zec SL, Granov N, Hukic M. The Impact of Antibiotic Consumption on Development of Acinetobacter Baumannii Resistance. Mater Sociomed 2017; 28:449-453. [PMID: 28144198 PMCID: PMC5239659 DOI: 10.5455/msm.2016.28.449-453] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
Aim: The aim of this study was to examine the impact of antibiotic consumption on development of antimicrobial resistance in Acinetobacter baumannii. Material and Methods: The study was conducted in University Clinical Center of Sarajevo. In our retrospective study Acinetobacter baumannii isolated in period from July 1st 2009 to December 31st 2012. Isolates were detected from different clinical samples including urine, wound swab, blood, bronchial aspirate and other samples which were collected from patients situated on various hospital wards. Clinical isolates belonged to one per patient in a given period of time. Results: Antimicrobial resistance was interpreted according to CLSI breakpoints. Consumption of antibiotics was analyzed according to recommendations of the ESAC-Net and current Acinetobacter baumannii classification. Pearson’s correlation showed a positive correlation between gentamicin consumption and emerging of resistance (p = 0.023). Conclusion: Increase in the antimicrobial use was followed with an increase in resistance of Acinetobacter baumannii isolates. Monitoring of antibiotic resistance and consumption is of a great importance in order to reduce the emergence and spread of antimicrobial resistant organisms in the health care settings.
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Affiliation(s)
- Djana Granov
- Clinical Microbiology, University Clinical Center Sarajevo, Bosnia and Herzegovina
| | | | - Svjetlana Loga Zec
- Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine University of Sarajevo, Bosnia and Herzegovina
| | - Nermir Granov
- Clinic for Cardio Surgery, University Clinical Center Sarajevo, Bosnia and Herzegovina
| | - Mirsada Hukic
- Institute for Biomedical Diagnostics and Research-Nalaz, Sarajevo, Bosnia and Herzegovina and International Burch University, Sarajevo, Bosnia and Herzegovina
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Bai J, Yang Y, Wang S, Gao L, Chen J, Ren Y, Ding W, Muhammad I, Li Y. Syringa oblata Lindl. Aqueous Extract Is a Potential Biofilm Inhibitor in S. suis. Front Pharmacol 2017; 8:26. [PMID: 28194111 PMCID: PMC5278344 DOI: 10.3389/fphar.2017.00026] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2016] [Accepted: 01/16/2017] [Indexed: 11/13/2022] Open
Abstract
Streptococcus suis (S. suis) is a zoonotic pathogen that causes severe disease symptoms in pigs and humans. Syringa oblata Lindl. distributed in the middle latitudes of Eurasia and North America were proved as the most development potential of Chinese Medicine. In this study, biofilm formation by S. suis decreased after growth with 1/2 MIC, 1/4 MIC, or 1/8 MIC of Syringa oblata Lindl. aqueous extract and rutin. Scanning electron microscopy analysis revealed the potential effect of Syringa oblata Lindl. aqueous extract and rutin against biofilm formation by S. suis. Using iTRAQ technology, comparative proteomic analyses was performed at two conditions: 1/2 MIC of Syringa oblata Lindl. aqueous extract treated and non-treated cells. The results revealed the existence of 28 proteins of varying amounts. We found that the majority of the proteins were related to cell growth and metabolism. We also found that Syringa oblata Lindl. Aqueous extract affected the synthesis enzymes. In summary, Syringa oblata Lindl. aqueous extract might be used to inhibit the biofilm formation effectively by S. suis, and the active ingredients of the Syringa oblate Lindl. aqueous extract is rutin. The content of rutin is 9.9 ± 0.089 mg/g dry weight.
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Affiliation(s)
- Jingwen Bai
- College of Veterinary Medicine, Northeast Agricultural University Harbin, China
| | - Yanbei Yang
- College of Veterinary Medicine, Northeast Agricultural University Harbin, China
| | - Shuai Wang
- College of Veterinary Medicine, Northeast Agricultural University Harbin, China
| | - Lingfei Gao
- College of Veterinary Medicine, Northeast Agricultural University Harbin, China
| | - Jianqing Chen
- College of Veterinary Medicine, Northeast Agricultural University Harbin, China
| | - Yongzhi Ren
- College of Veterinary Medicine, Northeast Agricultural University Harbin, China
| | - Wenya Ding
- College of Veterinary Medicine, Northeast Agricultural University Harbin, China
| | - Ishfaq Muhammad
- College of Veterinary Medicine, Northeast Agricultural University Harbin, China
| | - Yanhua Li
- College of Veterinary Medicine, Northeast Agricultural University Harbin, China
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Kentache T, Ben Abdelkrim A, Jouenne T, Dé E, Hardouin J. Global Dynamic Proteome Study of a Pellicle-forming Acinetobacter baumannii Strain. Mol Cell Proteomics 2017; 16:100-112. [PMID: 27799293 PMCID: PMC5217776 DOI: 10.1074/mcp.m116.061044] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2016] [Revised: 09/23/2016] [Indexed: 12/21/2022] Open
Abstract
For several decades, many bacteria, among which A. baumannii, have shown their ability to colonize the upper surface of static liquids, forming a biofilm at the air-liquid interface named pellicle. Despite the ubiquity of these pellicles in both natural and artificial environments, few studies have investigated this biofilm type. The present data set provides the first description of the whole proteome of A. baumannii cells grown as pellicle, using a label-free mass spectrometry approach. Results are in accord with the general findings reporting that sessile bacteria are far more resistant to detrimental conditions than their planktonic counterparts, by the accumulation of stress proteins. The present investigation also confirmed previous studies suggesting a correlation between the pellicle forming ability and the bacterial virulence. Indeed, we showed the up-regulation of numerous virulence factors during the pellicle growth, e.g. phospholipases, adhesion factors, as well as those of the GacAS Two-Component System (TCS) and Type 6 Secretion System (T6SS). We also highlighted that Bam and Tam systems, both related to the OM insertion machinery, play a critical role during pellicle biogenesis. Moreover, sessile bacteria activate several pathways, e.g. iron, magnesium, phosphate pathways, which allows for increasing the panel of nutrient sources.
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Affiliation(s)
- Takfarinas Kentache
- From the ‡CNRS; UMR 6270 Polymères, Biopolymères, Surfaces Laboratory, F-76821 Mont-Saint-Aignan, France
- §Normandie University, UR, France
| | - Ahmed Ben Abdelkrim
- From the ‡CNRS; UMR 6270 Polymères, Biopolymères, Surfaces Laboratory, F-76821 Mont-Saint-Aignan, France
- §Normandie University, UR, France
| | - Thierry Jouenne
- From the ‡CNRS; UMR 6270 Polymères, Biopolymères, Surfaces Laboratory, F-76821 Mont-Saint-Aignan, France
- §Normandie University, UR, France
- ¶PISSARO proteomic facility, IRIB, F-76821 Mont-Saint-Aignan, France
| | - Emmanuelle Dé
- From the ‡CNRS; UMR 6270 Polymères, Biopolymères, Surfaces Laboratory, F-76821 Mont-Saint-Aignan, France
- §Normandie University, UR, France
- ¶PISSARO proteomic facility, IRIB, F-76821 Mont-Saint-Aignan, France
| | - Julie Hardouin
- From the ‡CNRS; UMR 6270 Polymères, Biopolymères, Surfaces Laboratory, F-76821 Mont-Saint-Aignan, France;
- §Normandie University, UR, France
- ¶PISSARO proteomic facility, IRIB, F-76821 Mont-Saint-Aignan, France
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Inaba M, Matsuda N, Banno H, Jin W, Wachino JI, Yamada K, Kimura K, Arakawa Y. In vitro reduction of antibacterial activity of tigecycline against multidrug-resistant Acinetobacter baumannii with host stress hormone norepinephrine. Int J Antimicrob Agents 2016; 48:680-689. [PMID: 27842757 DOI: 10.1016/j.ijantimicag.2016.09.022] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2016] [Revised: 09/03/2016] [Accepted: 09/15/2016] [Indexed: 12/31/2022]
Abstract
The host stress hormone norepinephrine (NE), also called noradrenaline, is reported to augment bacterial growth and pathogenicity, but few studies have focused on the effect of NE on the activity of antimicrobials. The aim of this study was to clarify whether NE affects antimicrobial activity against multidrug-resistant Acinetobacter baumannii (MDR-AB). Time-kill studies of tigecycline (TIG) and colistin (COL) against MDR-AB as well as assays for factors contributing to antibiotic resistance were performed using MDR-AB clinical strains both in the presence and absence of 10 µM NE. In addition, expression of three efflux pump genes (adeB, adeJ and adeG) in the presence and absence of NE was analysed by quantitative reverse transcription PCR. Viable bacterial cell counts in TIG-supplemented medium containing NE were significantly increased compared with those in medium without NE. In contrast, NE had little influence on viable bacterial cell counts in the presence of COL. NE-supplemented medium resulted in an ca. 2 log increase in growth and in bacterial cell numbers adhering on polyurethane, silicone and polyvinylchloride surfaces. Amounts of biofilm in the presence of NE were ca. 3-fold higher than without NE. Expression of the adeG gene was upregulated 4-6-fold in the presence of NE. In conclusion, NE augmented factors contributing to antibiotic resistance and markedly reduced the in vitro antibacterial activity of TIG against MDR-AB. These findings suggest that NE treatment may contribute to the failure of TIG therapy in patients with MDR-AB infections.
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Affiliation(s)
- Masato Inaba
- Department of Emergency & Critical Care Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan; Department of Bacteriology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan
| | - Naoyuki Matsuda
- Department of Emergency & Critical Care Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan
| | - Hirotsugu Banno
- Department of Bacteriology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan
| | - Wanchun Jin
- Department of Bacteriology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan
| | - Jun-Ichi Wachino
- Department of Bacteriology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan
| | - Keiko Yamada
- Department of Bacteriology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan
| | - Kouji Kimura
- Department of Bacteriology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan
| | - Yoshichika Arakawa
- Department of Bacteriology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
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