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Arkiya S, Hesampour A, Esrafili A, Arasteh J. Effect of chitosan nanogels loaded with vancomycin and gamma interferon on TNF-α gene expression in macrophage cell line activated with methicillin-resistant Staphylococcus aureus (MRSA). IRANIAN JOURNAL OF MICROBIOLOGY 2024; 16:614-623. [PMID: 39534300 PMCID: PMC11551651 DOI: 10.18502/ijm.v16i5.16794] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/16/2024]
Abstract
Background and Objectives Staphylococcus aureus is an opportunistic pathogen that frequently leads to asymptomatic infections. Methicillin-resistant strains (MRSA) pose a significant threat as they are resistant to most commonly used antibiotics, complicating treatment efforts. This study aimed to develop chitosan nanogels loaded with vancomycin and IFN-γ and to assess the expression of the TNF-α gene in a cell line infected with MRSA. Materials and Methods Following the synthesis and confirmation of the chitosan nanogels, vancomycin and IFN-γ were incorporated into these nanogels. The synthesis was validated using DLS, FTIR, TEM, and SEM. Subsequently, the anti-bacterial efficacy of the nanogels was assessed. Finally, four groups of cell lines were designed: control, MRSA, chitosan nanogels and IFN-γ-vancomycin chitosan nanogels. After infection of the groups (except control) with MRSA, 5 μg/mL of nanogels, and nanogels (drug and IFN-γ) were added to groups 3 and 4, respectively. Then the expression of TNF-α gene in each group was analyzed by RT-PCR at 6 and 24 hours. Results At pH 6.5 and 7.4, the MIC of 1 μg/mL was obtained for free vancomycin, whereas that of IFN-γ-vancomycin nanogels at both pHs was respectively 8 and 64 μg/mL. The IC50 of chitosan nanogels and nanogels loaded with vancomycin-IFN-γ on RAW264.7 cells were 2.37 and 4.15 μg/mL in 24 hours, respectively. In group 4 in comparison to the MRSA group, TNF-α expression decreased significantly following 24 hours. Conclusion Loading of vancomycin and IFN-γ in the chitosan nanogel can reduce TNF-α gene expression on MRSA infected cell lines.
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Affiliation(s)
- Sahar Arkiya
- Department of Biology, Faculty of Science, Central Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Ardeshir Hesampour
- Department of Biology, Faculty of Science, Central Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Ali Esrafili
- Department of Environmental Health Engineering, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Javad Arasteh
- Department of Biology, Faculty of Science, Central Tehran Branch, Islamic Azad University, Tehran, Iran
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Costa M, Meirinhos C, Cunha E, Gomes D, Pereira M, Dias R, Tavares L, Oliveira M. Nisin Mutant Prevention Concentration and the Role of Subinhibitory Concentrations on Resistance Development by Diabetic Foot Staphylococci. Antibiotics (Basel) 2022; 11:antibiotics11070972. [PMID: 35884226 PMCID: PMC9311964 DOI: 10.3390/antibiotics11070972] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 07/14/2022] [Accepted: 07/15/2022] [Indexed: 12/10/2022] Open
Abstract
The most prevalent microorganism in diabetic foot infections (DFI) is Staphylococcus aureus, an important multidrug-resistant pathogen. The antimicrobial peptide nisin is a promising compound for DFI treatment, being effective against S. aureus. However, to avoid the selection of resistant mutants, correct drug therapeutic doses must be established, being also important to understand if nisin subinhibitory concentrations (subMIC) can potentiate resistant genes transfer between clinical isolates or mutations in genes associated with nisin resistance. The mutant selection window (MSW) of nisin was determined for 23 DFI S. aureus isolates; a protocol aiming to prompt vanA horizontal transfer between enterococci to clinical S. aureus was performed; and nisin subMIC effect on resistance evolution was assessed through whole-genome sequencing (WGS) applied to isolates subjected to a MEGA-plate assay. MSW ranged from 5–360 μg/mL for two isolates, from 5–540 μg/mL for three isolates, and from 5–720 μg/mL for one isolate. In the presence of nisin subMIC values, no transconjugants were obtained, indicating that nisin does not seem to promote vanA transfer. Finally, WGS analysis showed that incubation in the presence of nisin subMIC did not promote the occurrence of significant mutations in genes related to nisin resistance, supporting nisin application to DFI treatment.
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Affiliation(s)
- Margarida Costa
- CIISA—Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa, Av. da Universidade Técnica de Lisboa, 1300-477 Lisboa, Portugal; (M.C.); (C.M.); (D.G.); (L.T.); (M.O.)
- Laboratório Associado para Ciência Animal e Veterinária (AL4AnimalS), 1300-477 Lisbon, Portugal
| | - Cláudia Meirinhos
- CIISA—Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa, Av. da Universidade Técnica de Lisboa, 1300-477 Lisboa, Portugal; (M.C.); (C.M.); (D.G.); (L.T.); (M.O.)
- Laboratório Associado para Ciência Animal e Veterinária (AL4AnimalS), 1300-477 Lisbon, Portugal
| | - Eva Cunha
- CIISA—Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa, Av. da Universidade Técnica de Lisboa, 1300-477 Lisboa, Portugal; (M.C.); (C.M.); (D.G.); (L.T.); (M.O.)
- Laboratório Associado para Ciência Animal e Veterinária (AL4AnimalS), 1300-477 Lisbon, Portugal
- Correspondence:
| | - Diana Gomes
- CIISA—Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa, Av. da Universidade Técnica de Lisboa, 1300-477 Lisboa, Portugal; (M.C.); (C.M.); (D.G.); (L.T.); (M.O.)
- Laboratório Associado para Ciência Animal e Veterinária (AL4AnimalS), 1300-477 Lisbon, Portugal
| | - Marcelo Pereira
- Biosystems and Integrative Sciences Institute, Faculdade de Ciências, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal; (M.P.); (R.D.)
| | - Ricardo Dias
- Biosystems and Integrative Sciences Institute, Faculdade de Ciências, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal; (M.P.); (R.D.)
| | - Luís Tavares
- CIISA—Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa, Av. da Universidade Técnica de Lisboa, 1300-477 Lisboa, Portugal; (M.C.); (C.M.); (D.G.); (L.T.); (M.O.)
- Laboratório Associado para Ciência Animal e Veterinária (AL4AnimalS), 1300-477 Lisbon, Portugal
| | - Manuela Oliveira
- CIISA—Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa, Av. da Universidade Técnica de Lisboa, 1300-477 Lisboa, Portugal; (M.C.); (C.M.); (D.G.); (L.T.); (M.O.)
- Laboratório Associado para Ciência Animal e Veterinária (AL4AnimalS), 1300-477 Lisbon, Portugal
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Liu S, Hon K, Bouras GS, Psaltis AJ, Shearwin K, Wormald PJ, Vreugde S. APTC-C-SA01: A Novel Bacteriophage Cocktail Targeting Staphylococcus aureus and MRSA Biofilms. Int J Mol Sci 2022; 23:ijms23116116. [PMID: 35682794 PMCID: PMC9181636 DOI: 10.3390/ijms23116116] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Revised: 05/25/2022] [Accepted: 05/26/2022] [Indexed: 02/06/2023] Open
Abstract
The high infection and mortality rate of methicillin-resistant Staphylococcus aureus (MRSA) necessitates the urgent development of new treatment strategies. Bacteriophages (phages) have several advantages compared to antibiotics for the treatment of multi-drug-resistant bacterial infections, and thus provide a promising alternative to antibiotics. Here, S. aureus phages were isolated from patients and environmental sources. Phages were characterized for stability, morphology and genomic sequence and their bactericidal activity against the biofilm form of methicillin-susceptible Staphylococcus aureus (MSSA) and MRSA was investigated. Four S. aureus phages were isolated and tested against 51 MSSA and MRSA clinical isolates and reference strains. The phages had a broad host range of 82−94% individually and of >98% when combined and could significantly reduce the viability of S. aureus biofilms. The phages had a latent period of ≤20 min and burst size of >11 plaque forming units (PFU)/infected cell. Transmission electron microscopy (TEM) identified phages belonging to the family of Myoviridae. Genomic sequencing indicated the lytic nature of all four phages, with no identified resistance or virulence genes. The 4 phages showed a high complementarity with 49/51 strains (96%) sensitive to at least 2/4 phages tested. Furthermore, the frequency of bacteriophage insensitive mutant (BIM) generation was lower when the phages were combined into the phage cocktail APTC-C-SA01 than for bacteria exposed to each of the phages alone. In conclusion, APTC-C-SA01, containing four lytic S. aureus phages has the potential for further development as a treatment against MSSA and MRSA infections.
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Affiliation(s)
- Sha Liu
- Department of Surgery-Otolaryngology Head and Neck Surgery, Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Woodville, SA 5011, Australia; (S.L.); (K.H.); (G.S.B.); (A.J.P.); (P.-J.W.)
- Adelaide Medical School, The University of Adelaide, Adelaide, SA 5000, Australia
| | - Karen Hon
- Department of Surgery-Otolaryngology Head and Neck Surgery, Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Woodville, SA 5011, Australia; (S.L.); (K.H.); (G.S.B.); (A.J.P.); (P.-J.W.)
- Adelaide Medical School, The University of Adelaide, Adelaide, SA 5000, Australia
| | - George Spyro Bouras
- Department of Surgery-Otolaryngology Head and Neck Surgery, Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Woodville, SA 5011, Australia; (S.L.); (K.H.); (G.S.B.); (A.J.P.); (P.-J.W.)
- Adelaide Medical School, The University of Adelaide, Adelaide, SA 5000, Australia
| | - Alkis James Psaltis
- Department of Surgery-Otolaryngology Head and Neck Surgery, Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Woodville, SA 5011, Australia; (S.L.); (K.H.); (G.S.B.); (A.J.P.); (P.-J.W.)
- Adelaide Medical School, The University of Adelaide, Adelaide, SA 5000, Australia
| | - Keith Shearwin
- School of Biological Sciences, The University of Adelaide, Adelaide, SA 5000, Australia;
| | - Peter-John Wormald
- Department of Surgery-Otolaryngology Head and Neck Surgery, Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Woodville, SA 5011, Australia; (S.L.); (K.H.); (G.S.B.); (A.J.P.); (P.-J.W.)
- Adelaide Medical School, The University of Adelaide, Adelaide, SA 5000, Australia
| | - Sarah Vreugde
- Department of Surgery-Otolaryngology Head and Neck Surgery, Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Woodville, SA 5011, Australia; (S.L.); (K.H.); (G.S.B.); (A.J.P.); (P.-J.W.)
- Adelaide Medical School, The University of Adelaide, Adelaide, SA 5000, Australia
- Correspondence: ; Tel.: +61-8-8222-6928
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Akhtar F, Khan AU. Antimicrobial photodynamic therapy (aPDT) against vancomycin resistant Staphylococcus aureus (VRSA) biofilm disruption: A putative role of phagocytosis in infection control. Photodiagnosis Photodyn Ther 2021; 36:102552. [PMID: 34597830 DOI: 10.1016/j.pdpdt.2021.102552] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2021] [Revised: 09/21/2021] [Accepted: 09/24/2021] [Indexed: 10/20/2022]
Abstract
Biofilm mediated infections have major clinical impact. Staphylococcus aureus is a pathogen that frequently causes biofilm forming infections, such as those associated with medical devices and persistent wounds. Microorganisms embedded in biofilm are impervious to antibiotics and other antimicrobial agents, thus they are difficult to eliminate. The upsurge of multi-drug resistant strains makes treating such illnesses even more difficult. Therefore, new strategies are required to combat such type of infections. In this work, we have proposed an alternative therapeutic option to eradicate preformed biofilm of vancomycin resistant Staphylococcus aureus (VRSA) and enhanced phagocytosis by neutrophils in fresh human blood using curcumin mediated antimicrobial photodynamic therapy (aPDT).At sub-MIC of curcumin, different anti-biofilm assays and microscopic examinations were performed, followed by 20 J/cm2 of blue laser light irradiation which corresponds to 52 s only. The result showed significant disruption of VRSA biofilm. Moreover, when curcumin-aPDT treated VRSA biofilm was exposed to whole blood from healthy donors, it was nearly completely eradicated. The present study suggests that curcumin-aPDT enhanced phagocytosis may be a useful strategy for inactivating VRSA biofilms adhering to medical implant surfaces.
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Affiliation(s)
- Farheen Akhtar
- Medical Microbiology and Molecular Biology Lab., Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India
| | - Asad U Khan
- Medical Microbiology and Molecular Biology Lab., Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India.
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Wu Q, Sabokroo N, Wang Y, Hashemian M, Karamollahi S, Kouhsari E. Systematic review and meta-analysis of the epidemiology of vancomycin-resistance Staphylococcus aureus isolates. Antimicrob Resist Infect Control 2021; 10:101. [PMID: 34193295 PMCID: PMC8247230 DOI: 10.1186/s13756-021-00967-y] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Accepted: 06/03/2021] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Vancomycin‑resistant Staphylococcus aureus (VRSA) is a serious public health challenging concern worldwide. OBJECTIVES Therefore, the objective of present study of 62 published studies was to evaluate the prevalence of VRSA based on different years, areas, isolate source, antimicrobial susceptibility testing, and the genetic determinants. METHODS We searched the relevant articles that focused on the prevalence rates of VRSA in PubMed, Scopus, Embase, and Web of Science from 2000 to 2019. Statistical analyses were conducted using STATA software (version 14.0). RESULTS The prevalence of VRSA was 2% before 2006, 5% in 2006-2014, and 7% in 2015-2020 that showed a 3.5-fold increase in the frequency of VRSA between before 2006 and 2020 years. The prevalence of VRSA was 5% in Asia, 1% in Europe, 4% in America, 3% in South America, and 16% in Africa. The frequencies of VRSA isolated from clinical, non-clinical, and mixed samples were 6%, 7%, and 14%, respectively. The prevalence of VRSA was 12% using disk diffusion agar method, 7% using MIC-base methods, and 4% using mixed-methods. The prevalence of vanA, vanB, and vanC1 positive were 71%, 26%, and 4% among VRSA strains. The most prevalent genotype was staphylococcal cassette chromosomemec (SCCmec) II, which accounted for 57% of VRSA. The most prevalent staphylococcal protein A (spa) types were t002, t030, and t037. CONCLUSION The prevalence of VRSA has been increasing in recent years particularly in Africa/Asia than Europe/America. The most prevalent of genetic determinants associated with VRSA were vanA and SCCmec II. This study clarifies that the rigorous monitoring of definite antibiotic policy, regular surveillance/control of nosocomial-associated infections and intensive surveillance of vancomycin-resistance are required for preventing emergence and further spreading of VRSA.
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Affiliation(s)
- Qianxing Wu
- The Medical Lab of Hainan Cancer Hospital, Hainan Province, Haikou, 570312, People's Republic of China
| | - Niloofar Sabokroo
- Department of Microbiology, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Yujie Wang
- School of International Pharmaceutical Business, China Pharmaceutical University, Jiangsu Province, Nanjing, 211198, People's Republic of China.
| | - Marzieh Hashemian
- Clinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran
| | - Somayeh Karamollahi
- Clinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran
| | - Ebrahim Kouhsari
- Laboratory Sciences Research Center, Golestan University of Medical Sciences, Gorgan, Iran.
- Department of Laboratory Sciences, Faculty of Paramedicine, Golestan University of Medical Sciences, Gorgan, Iran.
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Zarghami V, Ghorbani M, Bagheri KP, Shokrgozar MA. Prevention the formation of biofilm on orthopedic implants by melittin thin layer on chitosan/bioactive glass/vancomycin coatings. JOURNAL OF MATERIALS SCIENCE. MATERIALS IN MEDICINE 2021; 32:75. [PMID: 34156547 PMCID: PMC8219550 DOI: 10.1007/s10856-021-06551-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/22/2020] [Accepted: 06/05/2021] [Indexed: 06/13/2023]
Abstract
Methicillin-resistant and Vancomycin-resistant Staphylococcus aureus bacteria (MRSA and VRSA, respectively) can seriously jeopardizes bone implants. This research aimed to examine the potential synergistic effects of Melittin and vancomycin in preventing MRSA and VRSA associated bone implant infections. Chitosan/bioactive glass nanoparticles/vancomycin composites were coated on hydrothermally etched titanium substrates by casting method. The composite coatings were coated by Melittin through drop casting technique. Melittin raised the proliferation of MC3T3 cells, making it an appropriate option as osteoinductive and antibacterial substance in coatings of orthopedic implants. Composite coatings having combined vancomycin and Melittin eliminated both planktonic and adherent MRSA and VRSA bacteria, whereas coatings containing one of them failed to kill the whole VRSA bacteria. Therefore, chitosan/bioactive glass/vancomycin/Melittin coating can be used as a bone implant coating because of its anti-infective properties.
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Affiliation(s)
- Vahid Zarghami
- Institute for Nanoscience & Nanotechnology, Sharif University of Technology, Tehran, Iran
| | - Mohammad Ghorbani
- Institute for Nanoscience & Nanotechnology, Sharif University of Technology, Tehran, Iran.
- Department of Materials Science and Engineering, Sharif University of Technology, Tehran, Iran.
| | - Kamran Pooshang Bagheri
- Venom & Biotherapeutics Molecules Laboratory, Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
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Bevalian P, Pashaei F, Akbari R, Pooshang Bagheri K. Eradication of vancomycin-resistant Staphylococcus aureus on a mouse model of third-degree burn infection by melittin: An antimicrobial peptide from bee venom. Toxicon 2021; 199:49-59. [PMID: 34087287 DOI: 10.1016/j.toxicon.2021.05.015] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 05/18/2021] [Accepted: 05/29/2021] [Indexed: 01/10/2023]
Abstract
Third-degree burn infections caused by antibiotic-resistant bacteria are of high clinical concern. Chemical antibiotics are not promising in eradication of bacterial infections. In this challenging condition, antimicrobial peptides (AMPs) are recently introduced as novel promising agents to overcome the issue. Accordingly, our study aimed to evaluate the efficiency of 'melittin' as natural peptide in bee venom, in eradicating vancomycin resistant Staphylococcus aureus (VRSA) on a mouse model of third-degree burn infection. In vitro pharmacological value of melittin was determined by examining its inhibitory and killing activities on VRSA isolates at different doses and time periods. The action mechanism of 'melittin' was evaluated by fluorescent release assay and Field Emission Scanning Electron Microscopy (FE-SEM) analyses. In vivo activity and toxicity of melittin were also examined on a mouse model of third-degree burn infection. The Minimum Inhibitory Concentration (MIC) and the Minimum Bactericidal Concentration (MBC) of melittin on all isolates ranged from '0.125-2 μg/mL' and '0.125-4 μg/mL', respectively. Rapid antibacterial activity of melittin on VRSA isolates was demonstrated by killing kinetics assays. Fluorometric and FE-SEM analyses indicated the membranolytic effects of melittin on VRSA isolates. The colonized VRSA bacteria were eradicated by melittin at 16 μg, in a single dose. No dermal toxicity and in vivo hemolysis were observed in the examined mice. The lack of in vivo toxicity of melittin along with its potent antibacterial activity indicated its promising therapeutic value as a topical drug against S. aureus associated third-degree burn infections.
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Affiliation(s)
- Parvaneh Bevalian
- Venom and Biotherapeutics Molecules Lab., Biotechnology Dept., Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
| | - Fatemeh Pashaei
- Venom and Biotherapeutics Molecules Lab., Biotechnology Dept., Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
| | - Reza Akbari
- Venom and Biotherapeutics Molecules Lab., Biotechnology Dept., Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran; Department of Microbiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, West Azerbaijan, Iran
| | - Kamran Pooshang Bagheri
- Venom and Biotherapeutics Molecules Lab., Biotechnology Dept., Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
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Synergistic action of phage phiIPLA-RODI and lytic protein CHAPSH3b: a combination strategy to target Staphylococcus aureus biofilms. NPJ Biofilms Microbiomes 2021; 7:39. [PMID: 33888725 PMCID: PMC8062563 DOI: 10.1038/s41522-021-00208-5] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Accepted: 03/19/2021] [Indexed: 02/02/2023] Open
Abstract
Staphylococcus aureus is considered a priority pathogen due to its increasing acquisition of antibiotic resistance determinants. Additionally, this microbe has the ability to form recalcitrant biofilms on different biotic and inert surfaces. In this context, bacteriophages and their derived lytic proteins may be a forward-looking strategy to help combat staphylococcal biofilms. However, these antimicrobials exhibit individual limitations that may be overcome by combining them with other compounds. This work investigates the combination of a phage-derived lytic protein, CHAPSH3b, and the virulent bacteriophage phiIPLA-RODI. The obtained results show the synergy between both antimicrobials for the treatment of 24-h-old S. aureus biofilms, with greater reductions in viable cell counts observed when phage and lysin are applied together compared to the individual treatments. Time-kill curves and confocal microscopy revealed that the fast antibacterial action of CHAPSH3b reduces the population up to 7 hours after initial exposure, which is subsequently followed by phage predation, limiting regrowth of the bacterial population. Moreover, at least 90% of bacteriophage insensitive mutants are susceptible to the lytic protein. Therefore, CHAPSH3b might help curtail the development of phage resistance during treatment. The combination of the lysin and phiIPLA-RODI also showed promising results in an ex vivo pig skin model of wound infection. Overall, the results of this study demonstrate that the combination of phage-derived lytic proteins and bacteriophages can be a viable strategy to develop improved antibiofilm products.
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Tuncer K, Gür B, Şenol O, Aydın MR, Gündoğdu Ö. New bone cements with Pluronic®F127 for prophylaxis and treatment of periprosthetic joint infections. J Mech Behav Biomed Mater 2021; 119:104496. [PMID: 33812290 DOI: 10.1016/j.jmbbm.2021.104496] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2021] [Revised: 03/21/2021] [Accepted: 03/23/2021] [Indexed: 11/16/2022]
Abstract
In line with the increase in orthopedic prosthetic surgeries, there has been a significant rise in periprosthetic joint infections (PJI) due to Methicillin-Resistant Staphylococcus Aureus (MRSA) bacteria. In case of infection, antibiotic-added spacers are temporarily placed into the periprosthetic region. With the release of antibiotics usually failing to work in fighting off infection, recent studies have centered around developing more effective approaches. New polymethylmethacrylate (PMMA) cement mixtures were prepared for this study with Pluronic®F127, bicarbonate, and citric acid addition. Optimal solutions were searched by monitoring vancomycin release on consecutive days with HPLC in in-vitro. The strengths of the samples were measured via four-point bending tests. Compared to conventional PMMA, strength values were observed to have improved by about 20% with 1.0 g of Pluronic®F127. According to HPLC studies, the highest increase for the area under the curve value was obtained for Pluronic®F127 doped mixture with a value of about 20%. It is understood from SEM and BET studies that addition of Pluronic®F127 helps increase porosity. The present study concludes that the optimum concentration of Pluronic®F127 could improve the strength and drug-releasing capacity of the spacer by increasing its porosity.
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Affiliation(s)
- Kutsi Tuncer
- Department of Orthopedics and Traumatology, Faculty of Medicine, Ataturk University, 25240, Erzurum, Turkey; Anesthesiology, Clinical Research Office, Atatürk University, 25240, Erzurum, Turkey
| | - Bahri Gür
- Department of Biochemistry, Faculty of Sciences and Arts, Iğdır University, 76000, Iğdır, Turkey.
| | - Onur Şenol
- Department of Analytical Chemistry, Faculty of Pharmacy, Atatürk University, 25240, Erzurum, Turkey
| | - Muhammet Raci Aydın
- Department of Mechanical Engineering, Faculty of Engineering, Iğdır University, 76000, Iğdır, Turkey.
| | - Ömer Gündoğdu
- Department of Mechanical Engineering, Faculty of Engineering, Iğdır University, 76000, Iğdır, Turkey; Department of Mechanical Engineering, Faculty of Engineering, Atatürk University, 25240, Erzurum, Turkey
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Titanium Oxide (TiO2) Nanoparticles for Treatment of Wound Infection. JOURNAL OF PURE AND APPLIED MICROBIOLOGY 2021. [DOI: 10.22207/jpam.15.1.41] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Wound infections is one of the major problems worldwide. Millions of people around the world require several medical treatments for wound infections. The extensive use of antibiotics to treat wound infection leads to emerging new microbial strains that are resistant to many antibiotics. There is a growing concern on the emergence and re-emergence of drug-resistant pathogens such as multi-resistant bacterial strains. Hence, the development of new antimicrobial compounds or the modification of those that already exist to improve antibacterial activity is a high research priority. Metallic nanoparticles (NPs) are considered as new alternative treatment for wound infection with superior antibacterial activity. In this study, new formulation of titanium oxide (TiO2) NPs with different sizes were synthesized and characterized. Genotoxicity, mutagenicity and antibacterial activities of TiO2 NPs against the causative agents of wound infection were investigated. Antibacterial activity of TiO2 NPs was conducted against three ATCC® bacterial strains: methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli and Pseudomonas aeruginosa. The results clearly illustrate a superior antibacterial activity of all newly formulated TiO2 NPs against the most causative agents of wound infection. Most of our TiO2 NPs showed non-genotoxic and non-mutagenic results at the maximum concentrations. Findings of this study will enhance the future of the therapeutic strategies against the resistant pathogenic strains that cause wound infections.
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Rungelrath V, DeLeo FR. Staphylococcus aureus, Antibiotic Resistance, and the Interaction with Human Neutrophils. Antioxid Redox Signal 2021; 34:452-470. [PMID: 32460514 PMCID: PMC8020508 DOI: 10.1089/ars.2020.8127] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Significance:Staphylococcus aureus is among the leading causes of bacterial infections worldwide. The high burden of S. aureus among human and animal hosts, which includes asymptomatic carriage and infection, is coupled with a notorious ability of the microbe to become resistant to antibiotics. Notably, S. aureus has the ability to produce molecules that promote evasion of host defense, including the ability to avoid killing by neutrophils. Recent Advances: Significant progress has been made to better understand S. aureus-host interactions. These discoveries include elucidation of the role played by numerous S. aureus virulence molecules during infection. Based on putative functions, a number of these virulence molecules, including S. aureus alpha-hemolysin and protein A, have been identified as therapeutic targets. Although it has not been possible to develop a vaccine that can prevent S. aureus infections, monoclonal antibodies specific for S. aureus virulence molecules have the potential to moderate the severity of disease. Critical Issues: Therapeutic options for treatment of methicillin-resistant S. aureus (MRSA) are limited, and the microbe typically develops resistance to new antibiotics. New prophylactics and/or therapeutics are needed. Future Directions: Research that promotes an enhanced understanding of S. aureus-host interaction is an important step toward developing new therapeutic approaches directed to moderate disease severity and facilitate treatment of infection. This research effort includes studies that enhance our view of the interaction of S. aureus with human neutrophils. Antioxid. Redox Signal. 34, 452-470.
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Affiliation(s)
- Viktoria Rungelrath
- Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA
| | - Frank R DeLeo
- Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA
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Akhtar F, Khan AU, Misba L, Akhtar K, Ali A. Antimicrobial and antibiofilm photodynamic therapy against vancomycin resistant Staphylococcus aureus (VRSA) induced infection in vitro and in vivo. Eur J Pharm Biopharm 2021; 160:65-76. [PMID: 33508436 DOI: 10.1016/j.ejpb.2021.01.012] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Revised: 12/22/2020] [Accepted: 01/20/2021] [Indexed: 02/08/2023]
Abstract
Biofilm mediated infection caused by multi-drug resistant bacteria are difficult to treat since it protects the microorganisms by host defense system, making them resistant to antibiotics and other antimicrobial agents. Combating such type of nosocomial infection, especially in immunocompromised patients, is an urgent need and foremost challenge faced by clinicians. Therefore, antimicrobial photodynamic therapy (aPDT) has been intensely pursued as an alternative therapy for bacterial infections. aPDT leads to the generation of reactive oxygen species (ROS) that destroy bacterial cells in the presence of a photosensitizer, visible light and oxygen. Here, we elucidated a possibility of its clinical application by reducing the treatment time and exposing curcumin to 20 J/cm2 of blue laser light, which corresponds to only 52 s to counteract vancomycin resistant Staphylococcus aureus (VRSA) both in vitro and in vivo. To understand the mechanism of action, the generation of total reactive oxygen species (ROS) was quantified by 2'-7'-dichlorofluorescein diacetate (DCFH-DA) and the type of phototoxicity was confirmed by fluorescence spectroscopic analysis. The data showed more production of singlet oxygen, indicating type-II phototoxicity. Different anti-biofilm assays (crystal violet and congo red assays) and microscopic studies were performed at sub-MIC concentration of curcumin followed by treatment with laser light against preformed biofilm of VRSA. The result showed significant reduction in the preformed biofilm formation. Finally, its therapeutic potential was validated in skin abrasion wistar rat model. The result showed significant inhibition of bacterial growth. Furthermore, immunomodulatory analysis with rat serum was performed. A significant reduction in expression of proinflammatory cytokines TNF-α and IL-6 were observed. Hence, we conclude that curcumin mediated aPDT with 20 J/cm2 of blue laser treatment (for 52 s) could be used against multi-drug resistant bacterial infections and preformed biofilm formation as a potential therapeutic approach.
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Affiliation(s)
- Farheen Akhtar
- Medical Microbiology and Molecular Biology Lab., Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India
| | - Asad U Khan
- Medical Microbiology and Molecular Biology Lab., Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India.
| | - Lama Misba
- Medical Microbiology and Molecular Biology Lab., Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India
| | - Kafil Akhtar
- Department of Pathology, JNMC, A.M.U., Aligarh, India
| | - Asif Ali
- Department of Biochemistry, F/o Medicine, JNMC A.M.U., Aligarh, India
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Rehman TU, Aslam R, Aqib AI, Mohsin M, Manzoor A, Shoaib M, Naseer MA, Hasan A, Sattar H, Fakhar-E-Alam Kulyar M, Muzammil I, Yao W. Phylogeny of hospital acquired MRSA, and its comparative phenotypic clinico-epidemiology with vancomycin resistant S. aureus (VRSA). Microb Pathog 2020; 149:104537. [PMID: 32980474 DOI: 10.1016/j.micpath.2020.104537] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Revised: 09/17/2020] [Accepted: 09/18/2020] [Indexed: 10/23/2022]
Abstract
Staphylococcus aureus is emerging as complicated pathogen because of its wide-ranging origin, multiple variants, and compromised antibiotic susceptibilities. Current study was planned to find lineage of hospital acquired methicillin resistant Staphylococcus aureus (HA-MRSA), and its comparative phenotypic clinico-epidemiology with vancomycin resistant S. aureus (VRSA). A total of (n = 200) samples were aseptically collected from wound, nose, and cerebrospinal fluid of patients from metropolitan and rural background hospitals along with on spot filling in of questionnaire. Phylogenetic analysis of HA-MRSA was identified by targeting mecA gene in S. aureus. At optimal tree branch length of 1.91 and evolutionary distance 0.1, high level sequence similarity (97%-99%) was observed with different strains of S. aureus isolated from both human and animal. Non-descriptive statistics at 5% probability found 61% S. aureus, while 43.44% of them were HA-MRSA, 92.62% VRSA, and 42.62% were both MRSA and VRSA. Among assumed risk factors, use of antibiotics, venous catheterization, chronic disease, pre-hospital visits, and ICU admitted patients showed significant association (p<0.05) with pathogen. HA-MRSA was 37.50%, 80%, and 37.50% sensitive to chloramphenicol, gentamicin, and oxacillin, respectively. While <50% of VRSA were sensitive against oxacillin, enoxacin, and chloramphenicol. A significant difference (p<0.05) of percentage responses of MRSA and VRSA at resistant, intermediate, and sensitive cadre against all antibiotics except chloramphenicol was obvious in this study. The Current study concluded higher prevalence of MRSA & VRSA, significant association of risk factors, limiting antibiotic susceptibility profile, and genetic transfer at animal-human interface which suggests further studies cum preventive strategies to be planned.
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Affiliation(s)
- Tayyab Ur Rehman
- Institute of Microbiology, University of Agriculture, Agriculture, Faisalabad, 38000, Pakistan
| | - Rizwan Aslam
- Institute of Microbiology, University of Agriculture, Agriculture, Faisalabad, 38000, Pakistan
| | - Amjad Islam Aqib
- Department of Medicine, Cholistan University of Veterinary and Animal Sciences, Bahawalpur, 63100, Pakistan.
| | - Mashkoor Mohsin
- Institute of Microbiology, University of Agriculture, Agriculture, Faisalabad, 38000, Pakistan
| | - Asad Manzoor
- Department of Clinical Medicine and Surgery, University of Agriculture, Faisalabad, 38000, Pakistan
| | - Muhammad Shoaib
- Institute of Microbiology, University of Agriculture, Agriculture, Faisalabad, 38000, Pakistan
| | - Muhammad Aamir Naseer
- Department of Clinical Medicine and Surgery, University of Agriculture, Faisalabad, 38000, Pakistan
| | - Ali Hasan
- Institute of Microbiology, University of Agriculture, Agriculture, Faisalabad, 38000, Pakistan
| | - Huma Sattar
- Institute of Biochemistry and Biotechnology, University of Veterinary and Animal Sciences, Lahore, Pakistan
| | | | - Iqra Muzammil
- Department of Clinical Medicine and Surgery, University of Agriculture, Faisalabad, 38000, Pakistan
| | - Wangyuan Yao
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, PR China.
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Haghi Ghahremanloi Olia A, Ghahremani M, Ahmadi A, Sharifi Y. Comparison of biofilm production and virulence gene distribution among community- and hospital-acquired Staphylococcus aureus isolates from northwestern Iran. INFECTION GENETICS AND EVOLUTION 2020; 81:104262. [PMID: 32109606 DOI: 10.1016/j.meegid.2020.104262] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/24/2019] [Revised: 02/20/2020] [Accepted: 02/21/2020] [Indexed: 01/03/2023]
Abstract
INTRODUCTION The emergence of antimicrobial-resistant isolates among Staphylococcus aureus and their genetic variations has become a major concern worldwide. The present study aims at comparing the biofilm formation and the genes encoding adhesion molecules in methicillin-susceptible, community- and hospital-acquired methicillin-resistant, vancomycin-intermediate and vancomycin-resistant S. aureus isolates. METHODOLOGY The current study was conducted on 60 S.aureus isolates, collected at Urmia University of Medical Sciences, Iran, between the years 2014 and 2015. The modified Congo-red agar and Microtiter plate methods were used to determine biofilm production. PCR was used to detect the genes which were associated with a protein family of staphylococcal microbial surface components recognizing adhesive matrix molecules. The data were analyzed using SPSS (IBM SPSS Statistics, version 16). RESULTS Of 60 isolates, 57 (95%) were biofilm producers. Unlike the bbp gene, which was only detected in 3 (5%) isolates, the eno and icaD genes were identified as the most prevalent as they were detected in 53 (88.3%) and 50 (85%) of 60 isolates, respectively. The dominant virulotype comprised eight genes (icaA, icaD, clfA, clfB, fnbA, cna, eno, ebpS) in eight isolates, six of which were community-acquired-MRSAs. CONCLUSION A high percentage of the S. aureus isolates could produce a biofilm which is more common among methicillin-susceptible isolates. The high frequency of eno and icaD genes suggests that these genes may synergistically function in the onset and progression of bacterial colonization and biofilm formation. Meanwhile, this ability may help the bacteria resist the exposure of antibacterial agents and cause severe infections.
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Affiliation(s)
- Ali Haghi Ghahremanloi Olia
- Department of Microbiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, West Azerbaijan, Iran
| | - Maryam Ghahremani
- Department of Microbiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, West Azerbaijan, Iran
| | - Ali Ahmadi
- Molecular Biology Research Center, Systems Biology and Poisonings Institute Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Yaeghob Sharifi
- Department of Microbiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, West Azerbaijan, Iran; Cellular and molecular research center, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, West Azerbaijan, Iran.
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Abstract
Staphylococci, and in particular Staphylococcus aureus, cause an extensive variety of infections in a range of hosts. The comprehensive analysis of staphylococcal genomes reveals mechanisms controlling the organism's biology, pathobiology, and dissemination. Whole-genome sequencing technologies led to a quantum leap in our understanding of bacterial genomes. The recent cost reduction of sequencing has resulted in unprecedented volumes of genomic information about S. aureus, one of the most sequenced bacterial species. Collecting, comparing, and interpreting big data is challenging, but fascinating insights have emerged. For example, it is becoming clearer which selective pressures staphylococci face in their habitats and which mechanisms allow this pathogen to adapt, survive, and spread. A key theme is the constant evolution of staphylococci as they alter their genome, exchange DNA, and adapt to new environments, leading to the emergence of increasingly successful, antibiotic-resistant, immune-evading, and host-adapted colonizers and pathogens. This article introduces the structure of staphylococcal genomes, details how genomes vary between strains, outlines the mechanisms of genetic variation, and describes the features of successful clones.
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Affiliation(s)
- Jodi A Lindsay
- St. George's, University of London, Institute of Infection and Immunity, London, United Kingdom
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Cong Y, Yang S, Rao X. Vancomycin resistant Staphylococcus aureus infections: A review of case updating and clinical features. J Adv Res 2019; 21:169-176. [PMID: 32071785 PMCID: PMC7015472 DOI: 10.1016/j.jare.2019.10.005] [Citation(s) in RCA: 276] [Impact Index Per Article: 46.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2019] [Revised: 10/02/2019] [Accepted: 10/09/2019] [Indexed: 01/08/2023] Open
Abstract
MRSA infection is a global threat to public health. Vancomycin is one of the first-line drugs for the treatment of MRSA infections. MRSA with complete resistance to vancomycin have emerged in recent years. The total number of VRSA isolates is updated in this paper. Resistance mechanisms, characteristics of VRSA infections, as well as clinical treatments are reviewed. The infection caused by methicillin-resistant Staphylococcus aureus (MRSA) is a global threat to public health. Vancomycin remains one of the first-line drugs for the treatment of MRSA infections. However, S. aureus isolates with complete resistance to vancomycin have emerged in recent years. Vancomycin-resistant S. aureus (VRSA) is mediated by a vanA gene cluster, which is transferred from vancomycin-resistant enterococcus. Since the first VRSA isolate was recovered from Michigan, USA in 2002, 52 VRSA strains have been isolated worldwide. In this paper, we review the latest progresses in VRSA, highlighting its resistance mechanism, characteristics of VRSA infections, as well as clinical treatments.
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Affiliation(s)
- Yanguang Cong
- Department of Clinical Laboratory, Traditional Medicine Hospital Affiliated to Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Sijin Yang
- Department of Cardiovascular Disease, Traditional Medicine Hospital Affiliated to Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Xiancai Rao
- Department of Microbiology, College of Basic Medical Sciences, Army Medical University (Third Military Medical University), Chongqing 400038, China
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Abstract
Staphylococcus aureus has been recognised as one of the important zoonotic pathogens. However, knowledge about the epidemiology and genetic characteristics of S. aureus in rabbits was limited. The aim of this study was to determine the characteristics of 281 S. aureus isolated from dead rabbits of nine rabbit farms in Fujian Province, China. All the isolates were characterised by multi-locus sequencing typing, detection of virulence factors and antimicrobial susceptibility test. The results showed that the 281 isolates were grouped into two sequence types, ST121 (13.52%, 38/281) and ST398 (86.48%, 243/281). Surprisingly, the ST121 strains were only recovered from the lung samples from one of the nine rabbit farms studied. In the 281 isolates, the virulence genes of nuc, hla, hlb, clfA, clfB and fnbpA were positive, whereas the sea, seb, tsst, eta and etb genes were negative. Notably, the 38 ST121 isolates carried the pvl gene. All the 281 isolates were methicillin-susceptible S. aureus, and the isolates were susceptible to most of the used antibiotics, except for streptomycin, kanamycin, azithromycin and penicillin, and the resistance rates of which were 23.84%, 19.57%, 16.01% and 11.03%, respectively. This study first described the epidemiology and characteristics of S. aureus in rabbits in Fujian Province, which will help in tracking the evolution of epidemic strains and preventing the rabbit-human transmission events.
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Low concentrations of acetic and formic acids enhance the inactivation of Staphylococcus aureus and Pseudomonas aeruginosa with pulsed electric fields. BMC Microbiol 2019; 19:73. [PMID: 30943901 PMCID: PMC6448289 DOI: 10.1186/s12866-019-1447-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2018] [Accepted: 03/28/2019] [Indexed: 02/07/2023] Open
Abstract
Background Skin infections, particularly caused by drug-resistant pathogens, represent a clinical challenge due to being a frequent cause of morbidity and mortality. The objectives of this study were to examine if low concentrations of acetic and formic acids can increase sensitivity of Staphylococcus aureus and Pseudomonas aeruginosa to pulsed electric field (PEF) and thus, promote a fast and efficient treatment methodology for wound treatment. Results We have shown that the combination of PEF (10–30 kV/cm) with organic acids (0.1% formic and acetic acids) increased the bactericidal properties of treatment. The effect was apparent for both acids. The proposed methodology allowed to reduce the energy of electrical pulses and the inhibitory concentrations of acids, while still maintain high efficiency of bacteria eradication. Conclusions Application of weak organic acids as bactericidal agents has many advantages over antibiotics because they do not trigger development of drug-resistance in bacteria. The combination with PEF can make the treatment effective even against biofilms. The results of this study are particularly useful for the development of new methodologies for the treatment of extreme cases of wound infections when the chemical treatment is no longer effective or hinders wound healing.
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Subramanian D, Natarajan J. RNA-seq analysis reveals resistome genes and signalling pathway associated with vancomycin-intermediate Staphylococcus aureus. Indian J Med Microbiol 2019; 37:173-185. [PMID: 31745016 DOI: 10.4103/ijmm.ijmm_18_311] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Context Vancomycin-intermediate Staphylococcus aureus remains one of the most prevalent multidrug-resistant pathogens causing healthcare infections that are difficult to treat. Aims This study uses a comprehensive computational analysis to systematically investigate various gene expression profiles of resistant and sensitive S. aureus strains on exposure to antibiotics. Settings and Design The transcriptional changes leading to the development of multiple antibiotic resistance were examined by an integrative analysis of nine differential expression experiments under selected conditions of vancomycin-intermediate and -sensitive strains for four different antibiotics using publicly available RNA-Seq datasets. Materials and Methods For each antibiotic, three experimental conditions for expression analysis were selected to identify those genes that are particularly involved in the development of resistance. The results were further scrutinised to generate a resistome that can be analysed for their role in the development or adaptation to antibiotic resistance. Results The 99 genes in the resistome are then compiled to create a multiple drug resistome of 25 known and novel genes identified to play a part in antibiotic resistance. The inclusion of agr genes and associated virulence factors in the identified resistome supports the role of agr quorum sensing system in multiple drug resistance. In addition, enrichment analysis also identified the kyoto encyclopedia of genes and genomes (KEGG) pathways - quorum sensing and two-component system pathways - in the resistome gene set. Conclusion Further studies on understanding the role of the identified molecular targets such as SAA6008_00181, SAA6008_01127, agrA, agrC and coa in adapting to the pressure of antibiotics at sub-inhibitory concentrations can help in learning the molecular mechanisms causing resistance to the pathogens as well as finding other potential therapeutics.
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Affiliation(s)
- Devika Subramanian
- Department of Bioinformatics, Data Mining and Text Mining Laboratory, Bharathiar University, Coimbatore, Tamil Nadu, India
| | - Jeyakumar Natarajan
- Department of Bioinformatics, Data Mining and Text Mining Laboratory, Bharathiar University, Coimbatore, Tamil Nadu, India
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Si W, Wang L, Usongo V, Zhao X. Colistin Induces S. aureus Susceptibility to Bacitracin. Front Microbiol 2018; 9:2805. [PMID: 30515145 PMCID: PMC6255926 DOI: 10.3389/fmicb.2018.02805] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2018] [Accepted: 10/31/2018] [Indexed: 01/11/2023] Open
Abstract
Bacitracin has been used in topical preparations with polymyxin B for bacterial infections. Colistin belongs to the polymyxin group of antibiotics and is effective against most Gram-negative bacilli. This study investigated whether colistin could affect the susceptibility of S. aureus to bacitracin. S. aureus isolates were first incubated with colistin and the susceptibility of S. aureus to bacitracin was increased. The effect of the combination of colistin and bacitracin on S. aureus was then confirmed by the checkerboard assay and the time-kill kinetics. The Triton X-100-induced autolysis was significantly increased after S. aureus was exposed to colistin. Exposure to colistin also led to a less positive charge on the cell surface and a significant leakage of Na+, Mg2, K+, Ca2+, Mn2+, Cu2+, and Zn2+. Finally, disruptions on the cell surface and an irregular morphology were observed when the bacteria were exposed to colistin and bacitracin. Bacitracin had a stronger antibacterial activity against S. aureus in the presence of colistin. This could be due to the fact that colistin damaged the bacterial membrane. This study suggests that combination of colistin with bacitracin has a potential for treating clinical S. aureus infections.
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Affiliation(s)
- Wei Si
- Department of Animal Science, McGill University, Montreal, QC, Canada
- College of Animal Science and Technology, Northwest A&F University, Yangling, China
| | - Liangliang Wang
- School of Pharmaceutical Sciences, Tsinghua University, Beijing, China
| | - Valentine Usongo
- Department of Animal Science, McGill University, Montreal, QC, Canada
| | - Xin Zhao
- Department of Animal Science, McGill University, Montreal, QC, Canada
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Tuning the biological activity of cationic anthraquinone analogues specifically toward Staphylococcus aureus. Eur J Med Chem 2018; 157:683-690. [PMID: 30130717 DOI: 10.1016/j.ejmech.2018.08.018] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2018] [Revised: 05/27/2018] [Accepted: 08/04/2018] [Indexed: 11/22/2022]
Abstract
Development of new antibacterial agents against drug resistant bacteria is an imminent task, especially against methicillin-resistant Staphylococcus aureus (MRSA). While MRSA can still be treated with broad spectrum antibiotics, the use of which often leads to the disruption of normal microbial flora leading to Clostridium difficile infection (CDI). Herein, a new class of antibacterial agent, cationic anthraquinone analogues specifically against MRSA, has been developed. Through the variation and optimization of substituents, these agents are selective toward MRSA, and not Gram negative bacteria which may avoid the problem of CDI. In addition, newly discovered lead compounds also show significantly reduced cytotoxicity against normal mammalian cells than cancerous cells. This interesting finding can alleviate the toxicity and side effect problems often associate with the use of antibiotics.
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Novickij V, Švedienė J, Paškevičius A, Markovskaja S, Lastauskienė E, Zinkevičienė A, Girkontaitė I, Novickij J. Induction of Different Sensitization Patterns of MRSA to Antibiotics Using Electroporation. Molecules 2018; 23:molecules23071799. [PMID: 30037022 PMCID: PMC6100619 DOI: 10.3390/molecules23071799] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2018] [Revised: 07/18/2018] [Accepted: 07/20/2018] [Indexed: 01/04/2023] Open
Abstract
Treatment of bacteria-associated infections is complicated and antibiotic treatment alone is often inadequate to overcome biofilm infections. Physical methods allow overcoming this problem and propose solutions that are non-dependent on drug resistance. In this work, we investigated the feasibility of pulsed electric fields for sensitization of MRSA to common antibiotics. We analyzed the efficacy of inactivation of methicillin-resistant Staphylococcus aureus in 5–20 kV/cm electric field separately and in combination with gentamicin, doxycycline, ciprofloxacin, sulfamethoxazole, and vancomycin. Combined treatment allowed using up to 1000-fold smaller concentrations of antibiotics to induce the same inactivation of S. aureus.
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Affiliation(s)
- Vitalij Novickij
- Institute of High Magnetic Fields, Vilnius Gediminas Technical University, Naugarduko st. 41, 03227 Vilnius, Lithuania.
| | - Jurgita Švedienė
- Laboratory of Biodeterioration Research, Nature Research Centre, Akademijos st. 2, 08412 Vilnius, Lithuania.
| | - Algimantas Paškevičius
- Laboratory of Biodeterioration Research, Nature Research Centre, Akademijos st. 2, 08412 Vilnius, Lithuania.
- Laboratory of Microbiology of the Centre of Laboratory Medicine, Vilnius University Hospital Santariškių Clinics, Santariskiu g. 2, 08406 Vilnius, Lithuania.
| | - Svetlana Markovskaja
- Laboratory of Mycology, Nature Research Centre, Žaliųjų ežerų st. 49, 08406 Vilnius, Lithuania.
| | - Eglė Lastauskienė
- Department of Microbiology and Biotechnology, Vilnius University, Sauletekio al. 7, 10257 Vilnius, Lithuania.
| | - Auksė Zinkevičienė
- State Research Institute Centre for Innovative Medicine, Department of Immunology, Santariškių st. 5, 08406 Vilnius, Lithuania.
| | - Irutė Girkontaitė
- State Research Institute Centre for Innovative Medicine, Department of Immunology, Santariškių st. 5, 08406 Vilnius, Lithuania.
| | - Jurij Novickij
- Institute of High Magnetic Fields, Vilnius Gediminas Technical University, Naugarduko st. 41, 03227 Vilnius, Lithuania.
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Sacadura-Leite E, Mendonça-Galaio L, Shapovalova O, Pereira I, Rocha R, Sousa-Uva A. Biological Hazards for Healthcare Workers: Occupational Exposure to Vancomycin-Resistant <b><i>Staphylococcus aureus</i></b> as an Example of a New Challenge. PORTUGUESE JOURNAL OF PUBLIC HEALTH 2018; 36:26-31. [DOI: 10.1159/000487746] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Infections are among the most important occupational risks for healthcare workers. Some infections can be prevented through vaccination but, in other cases, there are no vaccines to prevent them, as happens with infections from antimicrobial-resistant organisms. Precautions related with transmission route and contact isolation or respiratory isolation are very important in order to protect healthcare workers and other patients. In this paper, the authors reviewed biological hazards for healthcare workers and described the procedures undertaken by an occupational health department (OHD) of a Portuguese hospital where vancomycin-resistant <i>Staphylococcus aureus</i> (VRSA) was isolated from a patient, for the first time in Europe. After the VRSA strain isolation, healthcare workers were instructed to adopt contact preventive measures. Nasal swabs were cultured weekly in 33 healthcare workers for several weeks until the patients’ culture changed to negative. In the meantime, OHD prepared actions to adopt in case of VRSA colonization or infection in healthcare workers.
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Ouyang J, Sun F, Feng W, Xie Y, Ren L, Chen Y. Antimicrobial Activity of Galangin and Its Effects on Murein Hydrolases of Vancomycin-Intermediate Staphylococcus aureus (VISA) Strain Mu50. Chemotherapy 2017; 63:20-28. [PMID: 29145175 DOI: 10.1159/000481658] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2017] [Accepted: 09/19/2017] [Indexed: 11/19/2022]
Abstract
Backgroud: Antibiotic treatment for infections caused by vancomycin-intermediate Staphylococcus aureus (VISA) strains is challenging, and only a few effective and curative methods have been developed to combat these strains. This study aimed to investigate the antimicrobial activity of galangin against S. aureus and its effects on the murein hydrolases of VISA strain Mu50. This is the first report on these effects of galangin, and it may help to improve the treatment for VISA infections by demonstrating the effective use of galangin. METHODS Firstly, the minimum inhibitory concentration (MIC) and growth curve were used to investigate the antimicrobial activity of galangin against S. aureus. Secondly, transmission electron microscopy (TEM) was used to observe morphological changes of VISA strain Mu50. Thirdly, Triton X-100-induced autolysis and cell wall hydrolysis assays were performed to determine the activities of the murein hydrolases of Mu50. Finally, fluorescence real-time quantitative PCR was used to investigate the expression of the murein hydrolase-related Mu50 genes. RESULTS The results indicated that the MIC of galangin was 32 μg/mL against ATCC25293, N315, and Mu50, and galangin could significantly suppress the bacterial growth (p < 0.05) with concentrations of 4, 8 and 16 μg/mL, compared with control group (0 μg/mL). To explore the possible reasons of bacteriostatic effects of galangin, we observed morphological changes using TEM which showed that the division of Mu50 daughter cells treated with galangin was obviously inhibited. Considering the vital role of murein hydrolases in cellular division, assays were performed, and galangin markedly decreased Triton X-100-induced autolysis and cell wall hydrolysis. Galangin also significantly inhibited the expression of the murein hydrolase genes (atl, lytM, and lytN) and their regulatory genes (cidR, cidA, and cidB). CONCLUSIONS Our findings indicated that galangin can effectively inhibit murein hydrolase activity as well as the growth of VISA strain Mu50.
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Affiliation(s)
- Jing Ouyang
- Department of Pharmacy, Chongqing Public Health Medical Center, Chongqing, China
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Morris DO, Loeffler A, Davis MF, Guardabassi L, Weese JS. Recommendations for approaches to meticillin-resistant staphylococcal infections of small animals: diagnosis, therapeutic considerations and preventative measures.: Clinical Consensus Guidelines of the World Association for Veterinary Dermatology. Vet Dermatol 2017; 28:304-e69. [PMID: 28516494 DOI: 10.1111/vde.12444] [Citation(s) in RCA: 93] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/18/2017] [Indexed: 12/20/2022]
Abstract
BACKGROUND Multiple drug resistance (MDR) in staphylococci, including resistance to the semi-synthetic penicillinase-resistant penicillins such as meticillin, is a problem of global proportions that presents serious challenges to the successful treatment of staphylococcal infections of companion animals. OBJECTIVES The objective of this document is to provide harmonized recommendations for the diagnosis, prevention and treatment of meticillin-resistant staphylococcal infections in dogs and cats. METHODS The authors served as a Guideline Panel (GP) and reviewed the literature available prior to September 2016. The GP prepared a detailed literature review and made recommendations on selected topics. The World Association of Veterinary Dermatology (WAVD) provided guidance and oversight for this process. A draft of the document was presented at the 8th World Congress of Veterinary Dermatology (May 2016) and was then made available via the World Wide Web to the member organizations of the WAVD for a period of three months. Comments were solicited and posted to the GP electronically. Responses were incorporated by the GP into the final document. CONCLUSIONS Adherence to guidelines for the diagnosis, laboratory reporting, judicious therapy (including restriction of use policies for certain antimicrobial drugs), personal hygiene, and environmental cleaning and disinfection may help to mitigate the progressive development and dissemination of MDR staphylococci.
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Affiliation(s)
- Daniel O Morris
- Department of Clinical Studies - Philadelphia, School of Veterinary Medicine, University of Pennsylvania, 3900 Delancey St, Philadelphia, PA, 19104, USA
| | - Anette Loeffler
- Department of Clinical Sciences and Services, Royal Veterinary College, University of London, Hawkshead Lane, North Mymms, Hertfordshire, AL9 7TA, UK
| | - Meghan F Davis
- Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St, Baltimore, MD, 21205, USA
| | - Luca Guardabassi
- Department of Biomedical Sciences, School of Veterinary Medicine, Ross University, Basseterre, St Kitts and Nevis, West Indies
| | - J Scott Weese
- Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada, N1G 2W1
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Fang H, Fröding I, Gian B, Hæggman S, Tollström UB, Ullberg M, Nord CE. Methicillin-resistant Staphylococcus aureus in Stockholm, Sweden: Molecular epidemiology and antimicrobial susceptibilities to ceftaroline, linezolid, mupirocin and vancomycin in 2014. J Glob Antimicrob Resist 2016; 5:31-5. [PMID: 27436463 DOI: 10.1016/j.jgar.2016.01.012] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2015] [Revised: 01/15/2016] [Accepted: 01/21/2016] [Indexed: 11/16/2022] Open
Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) is a public health problem worldwide. The aim of the present study was to investigate the molecular epidemiology and antimicrobial susceptibilities of MRSA strains in Stockholm, Sweden in 2014. Pulsed-field gel electrophoresis (PFGE) was used to characterise the strains. Antimicrobial susceptibilities to ceftaroline, linezolid and mupirocin were determined by the disc diffusion method. Etest was used to determine vancomycin susceptibility and to confirm resistance to ceftaroline, mupirocin and linezolid in non-susceptible strains. High-level ceftaroline-resistant strains [minimum inhibitory concentration (MIC)≥4mg/L] were confirmed by the broth microdilution method. spa typing was carried out on strains that were non-susceptible to the antibiotics tested. In total, 743 consecutive non-duplicate MRSA strains recovered in Stockholm in 2014 were investigated. PFGE analysis of the isolates revealed a population with 271 different PFGE patterns and three non-typeable strains. No PFGE type accounted for >10% of all strains. The most common PFGE types were MRSA-00-02 (6.9%) and MRSA-05-02 (4.6%). MRSA-05-02 is a USA300-like strain. The antimicrobial susceptibilities of the strains were as follows: ceftaroline, 98.5%; linezolid, 100%; mupirocin, 99.3%; and vancomycin, 100%. Two strains with spa t001 displayed ceftaroline MICs of 4mg/L. Three strains with spa types t002, t064 and t437 showed high-level mupirocin resistance (MIC>1024mg/L). In conclusion, there was a diverse genetic population among the MRSA isolates and no predominant genotype was found. This study identified a few strains with high-level ceftaroline resistance, high-level mupirocin resistance and high-risk genotypes.
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Affiliation(s)
- Hong Fang
- Department of Clinical Microbiology, Karolinska University Hospital, Karolinska Institute, SE-141 86 Stockholm, Sweden
| | - Inga Fröding
- Department of Clinical Microbiology, Karolinska University Hospital, Karolinska Institute, SE-141 86 Stockholm, Sweden
| | - Boisan Gian
- Department of Clinical Microbiology, Karolinska University Hospital, Karolinska Institute, SE-141 86 Stockholm, Sweden
| | - Sara Hæggman
- Department of Microbiology, Public Health Agency of Sweden, SE-171 82 Solna, Sweden
| | | | - Måns Ullberg
- Department of Clinical Microbiology, Karolinska University Hospital, Karolinska Institute, SE-141 86 Stockholm, Sweden
| | - Carl Erik Nord
- Department of Clinical Microbiology, Karolinska University Hospital, Karolinska Institute, SE-141 86 Stockholm, Sweden.
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Hasan R, Acharjee M, Noor R. Prevalence of vancomycin resistant Staphylococcus aureus (VRSA) in methicillin resistant S. aureus (MRSA) strains isolated from burn wound infections. Tzu Chi Med J 2016; 28:49-53. [PMID: 28757721 PMCID: PMC5442891 DOI: 10.1016/j.tcmj.2016.03.002] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2015] [Revised: 10/12/2015] [Accepted: 03/04/2016] [Indexed: 02/07/2023] Open
Abstract
OBJECTIVES The increase in resistance of methicillin resistant Staphylococcus aureus (MRSA) strains to vancomycin has been perceived as a formidable threat in the therapeutic fields. The present study investigated the vancomycin resistance traits of MRSA isolates [vancomycin resistant S. aureus (VRSA)] collected from burn patients. MATERIALS AND METHODS Twenty-nine of 40 isolates of Staphylococcus spp. were identified as S. aureus which were further tested against 20 commercially available antibiotics to determine antibiotic susceptibility patterns. RESULTS Imipenem was the most potential antibiotic resulting in 90% sensitivity, followed by netilmicin, clindamycin, and nitrofurantoin (80% sensitivity). All isolates were found to be resistant to penicillin. Approximately 75% of them were found to be resistant to methicillin, oxacillin, azithromycin, cipro-floxacin, and tetracycline. Approximately 45% isolates exhibited resistance to amikacin, chloramphenicol, gentamycin, and tobramycin. Twenty-one of the 29 strains of S. aureus were MRSA, of which 11 were resistant to vancomycin when employing the disc diffusion method. However, when the broth micro-dilution procedure was used to measure the minimum inhibitory concentration (MIC) of vancomycin, eight isolates were resistant to vancomycin, six with an MIC of 32 μg/mL and two with an MIC of 64 μg/mL. CONCLUSION A significant fraction of VRSA was found among MRSA strains in this study, revealing the necessity for new and effective drugs against MRSA.
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Affiliation(s)
- Rashedul Hasan
- Department of Microbiology, Stamford University Bangladesh, Dhaka, Bangladesh
| | - Mrityunjoy Acharjee
- Department of Microbiology, Stamford University Bangladesh, Dhaka, Bangladesh
| | - Rashed Noor
- Department of Microbiology, Stamford University Bangladesh, Dhaka, Bangladesh
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Antibacterial Properties of Tebipenem Pivoxil Tablet, a New Oral Carbapenem Preparation against a Variety of Pathogenic Bacteria in Vitro and in Vivo. Molecules 2016; 21:62. [PMID: 26751436 PMCID: PMC6273992 DOI: 10.3390/molecules21010062] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2015] [Revised: 12/25/2015] [Accepted: 12/31/2015] [Indexed: 01/22/2023] Open
Abstract
Aims: To systemically investigate the in vitro and in vivo antibacterial properties of tebipenem pivoxil tablet. In addition, acute toxicity of this preparation was also studied. Methods: In vitro, minimum inhibitory concentration (MIC) or minimal inhibitory concentration (MBC) were determined by using the serial 2-fold broth or agar dilution methods. Further, cumulative MIC inhibition curves were then made to assess the antibacterial effects of the drug at various concentrations. In vivo, minimum lethal dose (MLD) in combination with maximum tolerance dose (MTD) was used to measure the acute toxicity of the tebipenem pivoxil tablet in mice. After that, sepsis mouse models challenged with Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae, respectively, were established to evaluate the anti-infective effect of this preparation. Results: The MIC90 values of tebipenem pivoxil against Gram-positive bacteria such as methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), methicillin-sensitive Staphylococcus epidermidis (MSSE), methicillin-resistant Staphylococcus epidermidis (MRSE), Pyogenic streptococcus, and Enterococcus faecalis were ≤0.125, 16, 0.5, 8, ≤0.125, and 32 μg/mL, respectively. Correspondingly, the MIC90 values of tebipenem pivoxil against Escherichia coli, Klebsiellapneumoniae, Enterobacter aerogenes, Haemophilus influenzae, Pseudomonas aeruginosa, and Acinetobacter baumannii were 1, 0.5, ≤0.125, 0.25, 64, 64 μg/mL, respectively. The MBC values of tebipenem pivoxil against Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae were 0.016–2, 0.063–32, 0.031–32 μg/mL, respectively. The acute toxicity study showed that the MLD of the tebipenem pivoxil tablet was 4.00 g/kg and the MTD was 3.40 g/kg in mice. In all the sepsis mouse models, the simultaneous administration of the tebipenem pivoxil tablets significantly reduced mortality of the sepsis-model mice as compared with the control. Furthermore, the survival rate in the tebipenem pivoxil tablet group was remarkably higher than that in the meropenem group in all the sepsis mouse models tested. In the sepsis model challenged with Staphylococcus aureus ATCC29213, Escherichia coli ATCC25922, Pseudomonas aeruginosa ATCC27853, and Pseudomonas aeruginosa clinical strain, respectively, tebipenem pivoxil tablet (100 mg/kg) displayed a better protective effect than tebipenem pivoxil granules (100 mg/kg). Conclusions: In summary, tebipenem pivoxil displays an excellent antibacterial activity against a variety of pathogenic bacteria in vitro. Importantly, tebipenem pivoxil tablet significantly protects the sepsis mice challenged with various pathogenic bacteria, which may provide a potential approach to treating bacterial sepsis in clinic.
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Monaco M, Pimentel de Araujo F, Cruciani M, Coccia EM, Pantosti A. Worldwide Epidemiology and Antibiotic Resistance of Staphylococcus aureus. Curr Top Microbiol Immunol 2016; 409:21-56. [PMID: 27025380 DOI: 10.1007/82_2016_3] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Staphylococcus aureus is an important human pathogen, responsible for infections in the community and the healthcare setting. Although much of the attention is focused on the methicillin-resistant "variant" MRSA, the methicillin-susceptible counterpart (MSSA) remains a prime species in infections. The epidemiology of S. aureus, especially of MRSA, showed a rapid evolution in the last years. After representing a typical nosocomial multidrug-resistant pathogen, MRSA has recently emerged in the community and among farmed animals thanks to its ability to evolve and adapt to different settings. Global surveillance has shown that MRSA represents a problem in all continents and countries where studies have been carried out, determining an increase in mortality and the need to use last-resource expensive antibiotics. S. aureus can easily acquire resistance to antibiotics and MRSA is characteristically multidrug resistant. Resistance to vancomycin, the principal anti-MRSA antibiotic is rare, although isolates with decreased susceptibility are recovered in many areas. Resistance to the more recently introduced antibiotics, linezolid and daptomycin, has emerged; however, they remain substantially active against the large majority of MSSA and MRSA. Newer antistaphylococcal drugs have been developed, but since their clinical use has been very limited so far, little is known about the emergence of resistance. Molecular typing techniques have allowed to identify the major successful clones and lineages of MSSA and MRSA, including high-risk clones, and to trace their diffusion. In the face of a continuously evolving scenario, this review depicts the most common clones circulating in different geographical areas and in different settings at present. Since the evolution of S. aureus will continue, it is important to maintain the attention on the epidemiology of S. aureus in the future with a global view.
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Affiliation(s)
- Monica Monaco
- Department of Infectious, Parasitic and Immuno-mediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy
| | - Fernanda Pimentel de Araujo
- Department of Infectious, Parasitic and Immuno-mediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy
| | - Melania Cruciani
- Department of Infectious, Parasitic and Immuno-mediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy
| | - Eliana M Coccia
- Department of Infectious, Parasitic and Immuno-mediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.
| | - Annalisa Pantosti
- Department of Infectious, Parasitic and Immuno-mediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.
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Outbreaks of Vancomycin-Resistant Enterococci in Hospital Settings: A Systematic Review and Calculation of the Basic Reproductive Number. Infect Control Hosp Epidemiol 2015; 37:289-94. [DOI: 10.1017/ice.2015.301] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
BACKGROUNDVancomycin-resistant enterococci (VRE) have spread worldwide.OBJECTIVETo systematically review VRE outbreaks and estimate the pooled basic reproductive rate (R0) of VRE.METHODSEligible studies criteria were (1) published within 10 years, (2) report outbreak details, (3) involve 1 center, (4) estimate epidemic duration, and (5) concern adults. Descriptive analysis included number of index cases, secondary cases, and screened patients; infection control measures; and definition of contact patients. R0 was estimated by the equation R0=(ln2) D/td+1, with D as the generation time and td as the doubling time.RESULTSThirteen VRE outbreaks were retained from 180 articles and, among them, 10 were kept for R0 calculation. The mean (range) number of index cases was 2.3 (1–8) and the mean (range) number of secondary cases was 15 (3–56). The mean (range) number of screened patients was 174 (32–509), with pooled VRE prevalence of 5.4% (95% CI, 4.5%–6.3%). Contact precautions were reported in 12 studies (92%), wards were closed in 7 (54%), with cohorting in 6 (46%). Two major screening policies were implemented: (1) a surveillance program in the unit or hospital (7 studies [54%]) and (2) screening of selected contact patients (6 studies [46%]). The pooled R0 of VRE was 1.32 (interquartile range, 1.03–1.46).CONCLUSIONWe discerned considerable heterogeneity in screening policies during VRE outbreaks. Pooled R0 was higher than 1, confirming the epidemic nature of VRE.Infect. Control Hosp. Epidemiol. 2016;37(3):289–394
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Okolie CE, Wooldridge KG, Turner DPJ, Cockayne A, James R. Development of a heptaplex PCR assay for identification of Staphylococcus aureus and CoNS with simultaneous detection of virulence and antibiotic resistance genes. BMC Microbiol 2015; 15:157. [PMID: 26242312 PMCID: PMC4525735 DOI: 10.1186/s12866-015-0490-9] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2014] [Accepted: 07/21/2015] [Indexed: 11/26/2022] Open
Abstract
Background Staphylococcal toxicity and antibiotic resistance (STAAR) have been menacing public health. Although vancomycin-resistant Staphylococcus aureus (VRSA) is currently not as widespread as methicillin-resistant S. aureus (MRSA), genome evolution of MRSA into VRSA, including strains engineered within the same patient under anti-staphylococcal therapy, may build up to future public health concern. To further complicate diagnosis, infection control and anti-microbial chemotherapy, non-sterile sites such as the nares and the skin could contain both S. aureus and coagulase-negative staphylococci (CoNS), either of which could harbour mecA the gene driving staphylococcal methicillin-resistance and required for MRSA-VRSA evolution. Results A new heptaplex PCR assay has been developed which simultaneously detects seven markers for: i) eubacteria (16S rRNA), ii) Staphylococcus genus (tuf), iii) Staphylococcus aureus (spa), iv) CoNS (cns), v) Panton-Valentine leukocidin (pvl), vi) methicillin resistance (mecA), and vii) vancomycin resistance (vanA). Following successful validation using 255 reference bacterial strains, applicability to analyse clinical samples was evaluated by direct amplification in spiked blood cultures (n = 89) which returned 100 % specificity, negative and positive predictive values. The new assay has LoD of 1.0x103 CFU/mL for the 16S rRNA marker and 1.0x104 CFU/mL for six other markers and completes cycling in less than one hour. Conclusion The speed, sensitivity (100 %), NPV (100 %) and PPV (100 %) suggest the new heptaplex PCR assay could be easily integrated into a routine diagnostic microbiology workflow. Detection of the cns marker allows for unique identification of CoNS in mono-microbial and in poly-microbial samples containing mixtures of CoNS and S. aureus without recourse to the conventional elimination approach which is ambiguous. In addition to the SA-CoNS differential diagnostic essence of the new assay, inclusion of vanA primers will allow microbiology laboratories to stay ahead of the emerging MRSA-VRSA evolution. To the best of our knowledge, the new heptaplex PCR assay is the most multiplexed among similar PCR-based assays for simultaneous detection of STAAR. Electronic supplementary material The online version of this article (doi:10.1186/s12866-015-0490-9) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Charles Emeka Okolie
- Centre for Healthcare Associated Infections, Centre for Biomolecular Sciences Building, The University of Nottingham, University Park, Nottingham, NG7 2RD, UK. .,Centre for Advanced Research and Development, Landmark University, Omu-Aran, Kwara State, Nigeria.
| | - Karl G Wooldridge
- Centre for Healthcare Associated Infections, Centre for Biomolecular Sciences Building, The University of Nottingham, University Park, Nottingham, NG7 2RD, UK.
| | - David P J Turner
- Centre for Healthcare Associated Infections, Centre for Biomolecular Sciences Building, The University of Nottingham, University Park, Nottingham, NG7 2RD, UK.
| | - Alan Cockayne
- Centre for Healthcare Associated Infections, Centre for Biomolecular Sciences Building, The University of Nottingham, University Park, Nottingham, NG7 2RD, UK.
| | - Richard James
- Centre for Healthcare Associated Infections, Centre for Biomolecular Sciences Building, The University of Nottingham, University Park, Nottingham, NG7 2RD, UK.
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Huang SH, Chen YC, Chuang YC, Chiu SK, Fung CP, Lu PL, Wang LS, Wu TL, Wang JT. Prevalence of vancomycin-intermediate Staphylococcus aureus (VISA) and heterogeneous VISA among methicillin-resistant S. aureus with high vancomycin minimal inhibitory concentrations in Taiwan: A multicenter surveillance study, 2012-2013. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2015; 49:701-707. [PMID: 26320398 DOI: 10.1016/j.jmii.2015.07.003] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/08/2015] [Revised: 06/12/2015] [Accepted: 07/06/2015] [Indexed: 10/23/2022]
Abstract
BACKGROUND/PURPOSE Intermediate-resistance and heteroresistance to vancomycin in methicillin-resistant Staphylococcus aureus (MRSA) is reported worldwide. A surveillance study in 2003 showed that the prevalence rates of vancomycin-intermediate S. aureus (VISA) and heterogeneous VISA (hVISA) in Taiwan were 0.2% and 0.7%, respectively. This study aimed to investigate the updated prevalence of VISA and hVISA in Taiwan. METHODS MRSA isolates from sterile sites with minimal inhibitory concentrations (MICs) of 1 μg/mL or more to vancomycin were collected from 15 participating hospitals in Taiwan. Enrolled MRSA isolates were submitted to antimicrobial susceptibility testing, staphylococcal cassette chromosome mec (SCCmec) element typing, and multilocus sequence typing. Isolates with vancomycin MIC of 1 μg/mL or 2 μg/mL were screened for vancomycin heterogeneous resistance by Etest glycopeptide-resistance detection (GRD). Those with positive GRD screening results were then analyzed by modified population analysis profiling-area under the curve method for confirmation of vancomycin heteroresistance. RESULTS Between 2012 and 2013, a total of 622 MRSA isolates from sterile sites with vancomycin MIC of 1 μg/mL or more were studied. The prevalence rates of hVISA and VISA among these isolates were 10.0% and 2.7%, respectively. The hVISA prevalence increased significantly compared to that in 2003. Compared with vancomycin-susceptible S. aureus, hVISA and VISA isolates were less susceptible to ciprofloxacin, clindamycin, daptomycin, gentamicin, rifampin, and trimethoprim/sulfamethoxazole, and are thus, more likely to have SCCmec II or III element. A twofold increase in either vancomycin or teicoplanin MIC doubled the probability of being hVISA. CONCLUSION Growing hVISA prevalence was highly suspected. Longitudinal surveillance of this phenomenon and monitoring of its clinical impact are necessary.
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Affiliation(s)
- Sung-Hsi Huang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Yee-Chun Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Yin-Ching Chuang
- Department of Medical Research, Chi Mei Medical Center, Tainan County, Taiwan
| | - Sheng-Kang Chiu
- Division of Infectious Diseases and Tropical Medicine, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chang-Phone Fung
- Section of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, National Yan-Ming University, Taipei, Taiwan
| | - Po-Liang Lu
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Lih-Shinn Wang
- Department of Infectious Diseases, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
| | - Tsu-Lan Wu
- Department of Laboratory Medicine, Chang Gung Memorial Hospital, Kweishan, Taoyuan, Taiwan
| | - Jann-Tay Wang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
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Couto N, Belas A, Kadlec K, Schwarz S, Pomba C. Clonal diversity, virulence patterns and antimicrobial and biocide susceptibility among human, animal and environmental MRSA in Portugal. J Antimicrob Chemother 2015; 70:2483-7. [PMID: 26048876 DOI: 10.1093/jac/dkv141] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2015] [Accepted: 04/29/2015] [Indexed: 11/12/2022] Open
Abstract
OBJECTIVES The objective of this study was to identify the Staphylococcus aureus clonal types currently circulating in animals, humans in contact with animals and the environment in Portugal based on genetic relatedness, virulence potential and antimicrobial/biocide susceptibility. METHODS Seventy-four S. aureus isolates from pets, livestock, the environment and humans in contact with animals were characterized by SCCmec typing, spa typing, PFGE and CC398-specific PCR, by antimicrobial and biocide susceptibility testing and by detection of resistance genes and genes for efflux pumps. Representative strains were analysed by DNA microarray and MLST. RESULTS The S. aureus isolates represented 13 spa types and 3 SCCmec types and belonged to three clonal complexes (CC5, CC22 and CC398). Most of the isolates were multiresistant and harboured the resistance genes that explained the resistance phenotype. The qacG and qacJ genes for biocide resistance were detected in 14 isolates (all MRSA CC398), while 4 isolates (3 CC5 and 1 CC22) had insertions in the -10 motif of the norA promoter. Isolates of the clonal lineages associated with pets (CC5 and CC22) harboured specific sets of virulence genes and often a lower number of resistance genes than isolates of the clonal lineage associated with livestock animals (CC398). CONCLUSIONS We found, for the first time in animals in Portugal, four strains belonging to CC5, including ST105-II, a lineage that has been previously reported as vancomycin-resistant S. aureus in Portugal. Moreover, for the first time the qacG and qacJ genes were detected in MRSA CC398 strains. Active surveillance programmes detecting MRSA not only in livestock animals but also in companion animals are urgently needed.
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Affiliation(s)
- Natacha Couto
- Antibiotic Resistance Laboratory, CIISA, Faculty of Veterinary Medicine, University of Lisbon, Lisbon, Portugal
| | - Adriana Belas
- Antibiotic Resistance Laboratory, CIISA, Faculty of Veterinary Medicine, University of Lisbon, Lisbon, Portugal
| | - Kristina Kadlec
- Institute of Farm Animal Genetics, Friedrich-Loeffler-Institut, Neustadt-Mariensee, Germany
| | - Stefan Schwarz
- Institute of Farm Animal Genetics, Friedrich-Loeffler-Institut, Neustadt-Mariensee, Germany
| | - Constança Pomba
- Antibiotic Resistance Laboratory, CIISA, Faculty of Veterinary Medicine, University of Lisbon, Lisbon, Portugal
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Morales-Cartagena A, Lalueza A, López-Medrano F, Juan RS, Aguado JM. Treatment of methicillin-resistant Staphylococcus aureus infections: Importance of high vancomycin minumum inhibitory concentrations. World J Clin Infect Dis 2015; 5:14-29. [DOI: 10.5495/wjcid.v5.i2.14] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2014] [Revised: 10/30/2014] [Accepted: 03/09/2015] [Indexed: 02/06/2023] Open
Abstract
Staphylococcus aureus (SA) infections remain a major cause of morbidity and mortality despite the availability of numerous effective anti-staphylococcal antibiotics. This organism is responsible for both nosocomial and community-acquired infections ranging from relatively minor skin and soft tissue infections to life-threatening systemic infections. The increasing incidence of methicillin-resistant strains has granted an increasing use of vancomycin causing a covert progressive increase of its minimum inhibitory concentration (MIC) (dubbed the MIC “creep”). In this way, the emergence of vancomycin-intermediate SA (VISA) strains and heteroresistant-VISA has raised concern for the scarcity of alternative treatment options. Equally alarming, though fortunately less frequent, is the emergence of vancomycin-resistant SA. These strains show different mechanisms of resistance but have similar problems in terms of therapeutic approach. Ultimately, various debate issues have arisen regarding the emergence of SA strains with a minimum inhibitory concentration sitting on the superior limit of the sensitivity range (i.e., MIC = 2 μg/mL). These strains have shown certain resilience to vancomycin and a different clinical behaviour regardless of vancomycin use, both in methicillin-resistant SA and in methicillin-sensitive SA. The aim of this text is to revise the clinical impact and consequences of the emergence of reduced vancomycin susceptibility SA strains, and the different optimal treatment options known.
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