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Iușan SAL, Lucaciu OP, Petrescu NB, Mirică IC, Toc DA, Albu S, Costache C. Exploring Peri-Implantitis Risk-Factors: A Cross-Sectional Study. Dent J (Basel) 2025; 13:148. [PMID: 40277478 PMCID: PMC12026288 DOI: 10.3390/dj13040148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2025] [Revised: 03/14/2025] [Accepted: 03/26/2025] [Indexed: 04/26/2025] Open
Abstract
Background/Objectives: With the increasing use of dental implants in edentulous patients and the high prevalence of peri-implantitis, understanding its microbial and risk factors is crucial. This study investigated Romanian patients from two private dental clinics in Cluj-Napoca, Romania, diagnosed with peri-implantitis, focusing on identifying the predominant bacterial species at affected sites compared with healthy implant sites. Additionally, we examined the impact of factors such as smoking, gender, age, and prosthetic restoration type on disease prevalence. Methods: This cross-sectional study, conducted between January 2023 and December 2024, included randomly selected patients who met the predefined inclusion and exclusion criteria. We enrolled 22 patients and 50 implants in the study. Data collected from medical records, clinical evaluations, and microbiological assessments were subsequently entered into a computerized database. Clinical data were analyzed using Social Science Statistics software(Jeremy Staangroom 2018). Bacterial samples were assessed, incubated, and subsequently identified using the Vitek 2 Compact System (BioMérieux, Marcy-l' Étoile, France). Results: Peri-implantitis incidence was found to be independent of gender, more prevalent in the mandible, and equally affected smokers and non-smokers. The disease involves a complex polymicrobial infection, with pathogenic bacteria triggering the condition and opportunistic bacteria sustaining it. Conclusions: Peri-implantitis is a complex polymicrobial infection that arises from the interaction of strict pathogenic bacteria and opportunistic bacteria. Peri-implantitis results from intricate interactions of local, systemic, and microbial factors. Identifying its causes is essential for developing effective treatments, with future research emphasizing the role of opportunistic bacteria in disease progression.
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Affiliation(s)
| | - Ondine Patricia Lucaciu
- Department of Oral Health, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Nausica Bianca Petrescu
- Department of Oral Health, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Ioana Codruța Mirică
- Department of Oral Health, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Dan-Alexandru Toc
- Department of Microbiology, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Silviu Albu
- II-nd Department of Otolaryngology, Iuliu Hatieganudisx University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Carmen Costache
- Department of Microbiology, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
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Lin YJ, Chen CH, Chang IYF, Chiang RL, Wang HY, Chiu CH, Chen YYM. Genomic and transcriptomic insights into the virulence and adaptation of shock syndrome-causing Streptococcus anginosus. MICROBIOLOGY (READING, ENGLAND) 2025; 171. [PMID: 39976625 DOI: 10.1099/mic.0.001535] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/10/2025]
Abstract
Streptococcus anginosus is a common isolate of the oral cavity and an opportunistic pathogen for systemic infections. Although the pyogenic infections caused by S. anginosus are similar to those caused by Streptococcus pyogenes, S. anginosus lacks most of the well-characterized virulence factors of S. pyogenes. To investigate the pathogenicity of S. anginosus, we analysed the genome of a newly identified S. anginosus strain, KH1, which was associated with toxic shock-like syndrome in an immunocompetent adolescent. The genome of KH1 contains nine genomic islands, two Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated systems and many phage-related proteins, indicating that the genome is influenced by prophages and horizontal gene transfer. Comparative genome analysis of 355 S. anginosus strains revealed a significant difference between the sizes of the pan genome and core genome, reflecting notable strain variations. We further analysed the transcriptomes of KH1 under conditions mimicking either the oral cavity or the bloodstream. We found that in an artificial saliva medium, the expression of a putative quorum quenching system and pyruvate oxidase for H2O2 production was upregulated, which could optimize the competitiveness of S. anginosus in the oral ecosystem. Conversely, in a modified serum medium, purine and glucan biosynthesis, competence and bacteriocin production were significantly upregulated, likely facilitating the survival of KH1 in the bloodstream. These findings indicate that S. anginosus can utilize diverse mechanisms to adapt to different environmental niches and establish infection, despite its lack of toxin production.
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Affiliation(s)
- Yu-Juan Lin
- Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC
| | - Chih-Ho Chen
- Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, ROC
| | - Ian Yi-Feng Chang
- Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan, ROC
- Department of Neurosurgery, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan, ROC
- Genomic Medicine Core Laboratory, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC
| | - Ruei-Lin Chiang
- Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan, ROC
| | - Hsing-Yi Wang
- Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC
| | - Cheng-Hsun Chiu
- Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Linkou, Taiwan, ROC
| | - Yi-Ywan M Chen
- Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC
- Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Linkou, Taiwan, ROC
- Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC
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Gil E, Hatcher J, de Saram S, Guy RL, Lamagni T, Brown JS. Streptococcus intermedius: an underestimated pathogen in brain infection? Future Microbiol 2025; 20:163-177. [PMID: 39552595 PMCID: PMC11792871 DOI: 10.1080/17460913.2024.2423524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Accepted: 10/28/2024] [Indexed: 11/19/2024] Open
Abstract
Streptococcus intermedius is an oral commensal organism belonging to the Streptococcus anginosus group (SAG). S. intermedius causes periodontitis as well as invasive, pyogenic infection of the central nervous system, pleural space or liver. Compared with other SAG organisms, S. intermedius has a higher mortality as well as a predilection for intracranial infection, suggesting it is likely to possess virulence factors that mediate specific interactions with the host resulting in bacteria reaching the brain. The mechanisms involved are not well described. Intracranial suppuration (ICS) due to S. intermedius infection can manifest as an abscess within the brain parenchyma, or a collection of pus (empyema) in the sub- or extra-dural space. These infections necessitate neurosurgery and prolonged antibiotic treatment and are associated with a considerable burden of morbidity and mortality. The incidence of ICS is increasing in several settings, with SAG species accounting for an increasing proportion of cases. There is a paucity of published literature regarding S. intermedius pathogenesis as well as few published genomes, hampering molecular epidemiological research. This perspective evaluates what is known about the clinical features and pathogenesis of ICS due to S. intermedius and explores hypothetical explanations why the incidence of these infections may be increasing.
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Affiliation(s)
- Eliza Gil
- UCL Respiratory, Division of Medicine, University College London, London, WC1E 6JF, UK
- Clinical Research Department, London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK
- Division of Infection, University College London Hospital, London, NW1 2BU, UK
- Department of Microbiology, Virology & Infection Control, Great Ormond Street Hospital for Children, NHS Foundation Trust, London, WC1N 1EH, UK
| | - James Hatcher
- Department of Microbiology, Virology & Infection Control, Great Ormond Street Hospital for Children, NHS Foundation Trust, London, WC1N 1EH, UK
- Department of Infection, Immunity & Inflammation, UCL Great Ormond Street Institute of Child Health, London, WC1N 1EH, UK
| | - Sophia de Saram
- Division of Infection, University College London Hospital, London, NW1 2BU, UK
| | - Rebecca L Guy
- Healthcare-Associated Infection & Antimicrobial Resistance Division, UK Health Security Agency, London, NW9 5EQ, United Kingdom
| | - Theresa Lamagni
- Healthcare-Associated Infection & Antimicrobial Resistance Division, UK Health Security Agency, London, NW9 5EQ, United Kingdom
| | - Jeremy S Brown
- UCL Respiratory, Division of Medicine, University College London, London, WC1E 6JF, UK
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Wang Y, Liu T, Sida Y, Zhu Y. Diversity and Evolution of the Mobilome Associated with Antibiotic Resistance Genes in Streptococcus anginosus. Microb Drug Resist 2025; 31:52-63. [PMID: 39837262 DOI: 10.1089/mdr.2024.0229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2025] Open
Abstract
Streptococcus anginosus is an important cause of pyogenic infections, bacteremia, and chronic maxillary sinusitis. Mobile genetic elements (MGEs) play a key role in lateral gene transfer, resulting in broad transfer of antibiotic resistance genes (ARGs). However, studies on ARG-associated MGEs in S. anginosus are still rare. To fill this gap, we used sequencing data from 11 clinical S. anginosus to characterize their mobilome diversity through comparative analysis. We found 47 well-characterized MGEs, including 23 putative integrative and conjugative elements (ICEs), 16 prophages/integrative mobilizable elements, and 8 composites. They were inserted into 16 positions, 4 of which were hot spots. A comprehensive analysis revealed that ARG-associated ICEs belong to four groups as follows: single serine integrases (ICESan49.2), tyrosine integrases (ICESan26.2), triple serine integrase ICEs (ICESan195.1), and a putative transposon integrase (ICESan49.1), all of which were similar to ICEs/transposons widely distributed among other streptococci. The eight composites were composed of multiple ICEs or transposons through successive accretion events (tandem or/and internal integration). In conclusion, we found that S. anginosus accumulates a variety of ARG-associated ICE/composites that may enable S. anginosus to serve as an ARG-associated MGE repository for other streptococci. The analysis of composites here provides a paradigm to further study mobilome evolution.
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Affiliation(s)
- Yingting Wang
- Department of Critical Care Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Taoran Liu
- Department of Critical Care Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Yi Sida
- Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China
| | - Yuanting Zhu
- NHC Key Laboratory of Assisted Circulation, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Department of Cardiology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
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Veronese P, Cella S, Giacometti A, Lapetina I, Maffini V, Pappalardo M, Rubini M, Ruozi MB, Dodi I. Invasive Streptococcus intermedius Infections in Children: Two Cases from a Pediatric Infectious Diseases Unit in Italy. Pathogens 2024; 13:1099. [PMID: 39770358 PMCID: PMC11728730 DOI: 10.3390/pathogens13121099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Revised: 11/26/2024] [Accepted: 12/05/2024] [Indexed: 01/16/2025] Open
Abstract
In recent years, an increasing number of reports have described invasive infections caused by bacteria from Streptococcus anginosus group (SAGs). S. intermedius seems to be more related with pleuropulmonary infections and abscess of the brain and deep soft tissues, and it is more likely to cause suppurative and non-bacteremic infections compared to other members of the same genus. We present two clinical cases of invasive S. intermedius infections in pediatric patients: a liver abscess case and a pansinusitis case associated with bilateral otomastoiditis and parapharyngeal abscess complicated by acute mediastinitis, thrombophlebitis of the cavernous sinus, and thrombosis of the cranial tract of the ipsilateral jugular vein. In both cases, prompt broad-spectrum antibiotic therapy and operative drainage of the collections resulted in a good clinical response with full recovery.
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Affiliation(s)
- Piero Veronese
- Pediatric Infectious Disease Unit, Children’s Hospital of Parma, 43126 Parma, Italy; (A.G.); (I.L.); (V.M.); (M.P.); (M.R.); (M.B.R.); (I.D.)
| | - Simone Cella
- Pediatric Radiology Unit, Institute of Radiology, University of Parma, 43126 Parma, Italy;
| | - Alessandra Giacometti
- Pediatric Infectious Disease Unit, Children’s Hospital of Parma, 43126 Parma, Italy; (A.G.); (I.L.); (V.M.); (M.P.); (M.R.); (M.B.R.); (I.D.)
| | - Irene Lapetina
- Pediatric Infectious Disease Unit, Children’s Hospital of Parma, 43126 Parma, Italy; (A.G.); (I.L.); (V.M.); (M.P.); (M.R.); (M.B.R.); (I.D.)
| | - Valentina Maffini
- Pediatric Infectious Disease Unit, Children’s Hospital of Parma, 43126 Parma, Italy; (A.G.); (I.L.); (V.M.); (M.P.); (M.R.); (M.B.R.); (I.D.)
| | - Marco Pappalardo
- Pediatric Infectious Disease Unit, Children’s Hospital of Parma, 43126 Parma, Italy; (A.G.); (I.L.); (V.M.); (M.P.); (M.R.); (M.B.R.); (I.D.)
| | - Monica Rubini
- Pediatric Infectious Disease Unit, Children’s Hospital of Parma, 43126 Parma, Italy; (A.G.); (I.L.); (V.M.); (M.P.); (M.R.); (M.B.R.); (I.D.)
| | - Maria Beatrice Ruozi
- Pediatric Infectious Disease Unit, Children’s Hospital of Parma, 43126 Parma, Italy; (A.G.); (I.L.); (V.M.); (M.P.); (M.R.); (M.B.R.); (I.D.)
| | - Icilio Dodi
- Pediatric Infectious Disease Unit, Children’s Hospital of Parma, 43126 Parma, Italy; (A.G.); (I.L.); (V.M.); (M.P.); (M.R.); (M.B.R.); (I.D.)
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Qian ST, Zhao HY, Xie FF, Liu QS, Cai DL. Streptococcus anginosus in the development and treatment of precancerous lesions of gastric cancer. World J Gastrointest Oncol 2024; 16:3771-3780. [PMID: 39350992 PMCID: PMC11438778 DOI: 10.4251/wjgo.v16.i9.3771] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Revised: 05/22/2024] [Accepted: 06/06/2024] [Indexed: 09/09/2024] Open
Abstract
The microbiota is strongly association with cancer. Studies have shown significant differences in the gastric microbiota between patients with gastric cancer (GC) patients and noncancer patients, suggesting that the microbiota may play a role in the development of GC. Although Helicobacter pylori (H. pylori) infection is widely recognized as a primary risk factor for GC, recent studies based on microbiota sequencing technology have revealed that non-H. pylori microbes also have a significant impact on GC. A recent study discovered that Streptococcus anginosus (S. anginosus) is more prevalent in the gastric mucosa of patients with GC than in that of those without GC. S. anginosus infection can spontaneously induce chronic gastritis, mural cell atrophy, mucoid chemotaxis, and heterotrophic hyperplasia, which promote the development of precancerous lesions of GC (PLGC). S. anginosus also disrupts the gastric barrier function, promotes the proliferation of GC cells, and inhibits apoptosis. However, S. anginosus is underrepresented in the literature. Recent reports suggest that it may cause precancerous lesions, indicating its emerging pathogenicity. Modern novel molecular diagnostic techniques, such as polymerase chain reaction, genetic testing, and Ultrasensitive Chromosomal Aneuploidy Detection, can be used to gastric precancerous lesions via microbial markers. Therefore, we present a concise summary of the relationship between S. anginosus and PLGC. Our aim was to further investigate new methods of preventing and treating PLGC by exploring the pathogenicity of S. anginosus on PLGC.
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Affiliation(s)
- Su-Ting Qian
- Department of Digestive, Hangzhou Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Hangzhou 310007, Zhejiang Province, China
| | - Hao-Yu Zhao
- Department of Digestive, Hangzhou Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Hangzhou 310007, Zhejiang Province, China
| | - Fei-Fei Xie
- Department of Digestive, Hangzhou Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Hangzhou 310007, Zhejiang Province, China
| | - Qing-Sheng Liu
- Science and Education Section, Hangzhou Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Hangzhou 310007, Zhejiang Province, China
| | - Dan-Li Cai
- Intensive Care Unit, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou 311122, Zhejiang Province, China
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Tomoyasu T, Tabata A, Nagamune H. Identification of mutations resulting in derepression of the intermedilysin gene by sequential mutagenesis of its promoter region in Streptococcus intermedius. FEMS Microbiol Lett 2024; 371:fnae063. [PMID: 39104214 DOI: 10.1093/femsle/fnae063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Revised: 07/06/2024] [Accepted: 08/02/2024] [Indexed: 08/07/2024] Open
Abstract
Streptococcus intermedius secretes the human-specific cytolysin intermedilysin (ILY), a crucial factor in the pathogenicity of this bacterium. Previously, we reported that a lactose phosphotransferase repressor (LacR) represses ily expression, and that its mutation increases ILY production. Interestingly, UNS40, a strain isolated from a liver abscess, produces high levels of ILY despite the absence of mutations in the lacR promoter and coding regions. Our results showed that a G > A mutation at the -90th position from the transcription start point in the UNS40 ily promoter region increased hemolytic activity and decreased the binding ability to LacR. To elucidate the regions involved in the repression of ily expression, we generated mutant strains, in which point or deletion mutations were introduced into the ily promoter region, and then compared their hemolytic activity. Among the point mutations, -120 C > A and -90 G > A and their flanking mutations increased hemolytic activity. These results indicated that these mutations may increase the virulence of S. intermedius.
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Affiliation(s)
- Toshifumi Tomoyasu
- Department of Bioengineering, Division of Bioscience and Bioindustry, Graduate School of Technology, Industrial and Social Sciences, Tokushima University Graduate School, 2-1 Minami-Jousanjima-Cho, Tokushima, Tokushima 770-8513, Japan
| | - Atsushi Tabata
- Department of Bioengineering, Division of Bioscience and Bioindustry, Graduate School of Technology, Industrial and Social Sciences, Tokushima University Graduate School, 2-1 Minami-Jousanjima-Cho, Tokushima, Tokushima 770-8513, Japan
| | - Hideaki Nagamune
- Department of Bioengineering, Division of Bioscience and Bioindustry, Graduate School of Technology, Industrial and Social Sciences, Tokushima University Graduate School, 2-1 Minami-Jousanjima-Cho, Tokushima, Tokushima 770-8513, Japan
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Yamada T, Yamamori Y, Matsuda N, Nagamune H, Ohkura K, Tomoyasu T, Tabata A. Streptolysin S induces pronounced calcium-ion influx-dependent expression of immediate early genes encoding transcription factors. Sci Rep 2023; 13:13720. [PMID: 37608082 PMCID: PMC10444759 DOI: 10.1038/s41598-023-40981-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Accepted: 08/19/2023] [Indexed: 08/24/2023] Open
Abstract
Anginosus group streptococci (AGS) are opportunistic human pathogens of the oral cavity. The β-hemolytic subgroup of Streptococcus anginosus subsp. anginosus secretes streptolysin S (SLS) and exhibits not only hemolytic activity but also cytotoxicity toward cultured human cell lines. However, the detailed mechanism of action of SLS and the cellular responses of host cells have not yet been fully clarified. To determine the pathogenic potential of SLS-producing β-hemolytic S. anginosus subsp. anginosus, the SLS-dependent response induced in the human oral squamous cell carcinoma HSC-2 cells was investigated to determine the pathogenic potential of SLS-producing β-hemolytic S. anginosus subsp. anginosus. This study revealed that the Ca2+ influx and the expression of immediate early genes (IEGs) encoding transcription factors such as early growth responses (EGRs) and activator protein-1 (AP-1) were greatly increased in HSC-2 cells incubated with the culture supernatant of SLS-producing β-hemolytic S. anginosus subsp. anginosus. Moreover, this SLS-dependent increase in expression was significantly suppressed by Ca2+ chelation, except for jun. These results suggest that SLS caused Ca2+ influx into the cells following greatly enhanced expression of IEG-encoding transcription factors. The results of this study may help in understanding the pathogenicity of SLS-producing AGS.
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Affiliation(s)
- Takuya Yamada
- Department of Biological Science and Technology, Life System, Institute of Technology and Science, Tokushima University Graduate School, 2-1 Minamijousanjima-Cho, Tokushima, Tokushima, 770-8506, Japan
| | - Yugo Yamamori
- Faculty of Bioscience and Bioindustry, Bioengineering Course, Tokushima University, 2-1 Minamijousanjima-Cho, Tokushima, Tokushima, 770-8513, Japan
| | - Nanami Matsuda
- Faculty of Bioscience and Bioindustry, Bioengineering Course, Tokushima University, 2-1 Minamijousanjima-Cho, Tokushima, Tokushima, 770-8513, Japan
| | - Hideaki Nagamune
- Department of Biological Science and Technology, Life System, Institute of Technology and Science, Tokushima University Graduate School, 2-1 Minamijousanjima-Cho, Tokushima, Tokushima, 770-8506, Japan
- Faculty of Bioscience and Bioindustry, Bioengineering Course, Tokushima University, 2-1 Minamijousanjima-Cho, Tokushima, Tokushima, 770-8513, Japan
- Department of Bioengineering, Division of Bioscience and Bioindustry, Graduate School of Technology, Industrial and Social Sciences, Tokushima University Graduate School, 2-1 Minamijousanjima-Cho, Tokushima, Tokushima, 770-8513, Japan
| | - Kazuto Ohkura
- Division of Clinical Pharmacy and Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3 Minamitamagaki-Cho, Suzuka, Mie, 513-8670, Japan
| | - Toshifumi Tomoyasu
- Department of Biological Science and Technology, Life System, Institute of Technology and Science, Tokushima University Graduate School, 2-1 Minamijousanjima-Cho, Tokushima, Tokushima, 770-8506, Japan
- Faculty of Bioscience and Bioindustry, Bioengineering Course, Tokushima University, 2-1 Minamijousanjima-Cho, Tokushima, Tokushima, 770-8513, Japan
- Department of Bioengineering, Division of Bioscience and Bioindustry, Graduate School of Technology, Industrial and Social Sciences, Tokushima University Graduate School, 2-1 Minamijousanjima-Cho, Tokushima, Tokushima, 770-8513, Japan
| | - Atsushi Tabata
- Department of Biological Science and Technology, Life System, Institute of Technology and Science, Tokushima University Graduate School, 2-1 Minamijousanjima-Cho, Tokushima, Tokushima, 770-8506, Japan.
- Faculty of Bioscience and Bioindustry, Bioengineering Course, Tokushima University, 2-1 Minamijousanjima-Cho, Tokushima, Tokushima, 770-8513, Japan.
- Department of Bioengineering, Division of Bioscience and Bioindustry, Graduate School of Technology, Industrial and Social Sciences, Tokushima University Graduate School, 2-1 Minamijousanjima-Cho, Tokushima, Tokushima, 770-8513, Japan.
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García E. Two putative glutamate decarboxylases of Streptococcus pneumoniae as possible antigens for the production of anti-GAD65 antibodies leading to type 1 diabetes mellitus. Int Microbiol 2023; 26:675-690. [PMID: 37154976 PMCID: PMC10165594 DOI: 10.1007/s10123-023-00364-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Revised: 04/13/2023] [Accepted: 04/21/2023] [Indexed: 05/10/2023]
Abstract
Type 1 diabetes mellitus (T1DM) has been increasing in prevalence in the last decades and has become a global burden. Autoantibodies against human glutamate decarboxylase (GAD65) are among the first to be detected at the onset of T1DM. Diverse viruses have been proposed to be involved in the triggering of T1DM because of molecular mimicry, i.e., similarity between parts of some viral proteins and one or more epitopes of GAD65. However, the possibility that bacterial proteins might also be responsible for GAD65 mimicry has been seldom investigated. To date, many genomes of Streptococcus pneumoniae (the pneumococcus), a prominent human pathogen particularly prevalent among children and the elderly, have been sequenced. A dataset of more than 9000 pneumococcal genomes was mined and two different (albeit related) genes (gadA and gadB), presumably encoding two glutamate decarboxylases similar to GAD65, were found. The various gadASpn alleles were present only in serotype 3 pneumococci belonging to the global lineage GPSC83, although some homologs have also been discovered in two subspecies of Streptococcus constellatus (pharyngis and viborgensis), an isolate of the group B streptococci, and several strains of Lactobacillus delbrueckii. Besides, gadBSpn alleles are present in > 10% of the isolates in our dataset and represent 16 GPSCs with 123 sequence types and 20 different serotypes. Sequence analyses indicated that gadA- and gadB-like genes have been mobilized among different bacteria either by prophage(s) or by integrative and conjugative element(s), respectively. Substantial similarities appear to exist between the putative pneumococcal glutamate decarboxylases and well-known epitopes of GAD65. In this sense, the use of broader pneumococcal conjugate vaccines such as PCV20 would prevent the majority of serotypes expressing those genes that might potentially contribute to T1DM. These results deserve upcoming studies on the possible involvement of S. pneumoniae in the etiopathogenesis and clinical onset of T1DM.
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Affiliation(s)
- Ernesto García
- Departamento de Biotecnología Microbiana y de Plantas, Centro de Investigaciones Biológicas Margarita Salas (CSIC), Ramiro de Maeztu 9, 28040, Madrid, Spain.
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Bauer R, Haider D, Grempels A, Roscher R, Mauerer S, Spellerberg B. Diversity of CRISPR-Cas type II-A systems in Streptococcus anginosus. Front Microbiol 2023; 14:1188671. [PMID: 37396379 PMCID: PMC10310304 DOI: 10.3389/fmicb.2023.1188671] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Accepted: 05/25/2023] [Indexed: 07/04/2023] Open
Abstract
Streptococcus anginosus is a commensal Streptococcal species that is often associated with invasive bacterial infections. However, little is known about its molecular genetic background. Many Streptococcal species, including S. anginosus, harbor clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems. A CRISPR-Cas type II-A system as well as a type II-C system have been reported for this species. To characterize the CRISPR-Cas type II systems of S. anginosus in more detail, we conducted a phylogenetic analysis of Cas9 sequences from CRISPR-Cas type II systems with a special focus on streptococci and S. anginosus. In addition, a phylogenetic analysis of S. anginosus strains based on housekeeping genes included in MLST analysis, was performed. All analyzed Cas9 sequences of S. anginosus clustered with the Cas9 sequences of CRISPR type II-A systems, including the Cas9 sequences of S. anginosus strains reported to harbor a type II-C system. The Cas9 genes of the CRISPR-Cas type II-C systems of other bacterial species separated into a different cluster. Moreover, analyzing the CRISPR loci found in S. anginosus, two distinct csn2 genes could be detected, a short form showing high similarity to the canonical form of the csn2 gene present in S. pyogenes. The second CRISPR type II locus of S. anginosus contained a longer variant of csn2 with close similarities to a csn2 gene that has previously been described in Streptococcus thermophilus. Since CRISPR-Cas type II-C systems do not contain a csn2 gene, the S. anginosus strains reported to have a CRISPR-Cas type II-C system appear to carry a variation of CRISPR-Cas type II-A harboring a long variant of csn2.
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11
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Prasad A, Ene A, Jablonska S, Du J, Wolfe AJ, Putonti C. Comparative Genomic Study of Streptococcus anginosus Reveals Distinct Group of Urinary Strains. mSphere 2023; 8:e0068722. [PMID: 36744899 PMCID: PMC10117062 DOI: 10.1128/msphere.00687-22] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Accepted: 01/16/2023] [Indexed: 02/07/2023] Open
Abstract
Streptococcus anginosus is a prevalent member of the human flora. While it has been found in the microbiota of "healthy" asymptomatic individuals, it has also been associated with genitourinary tract infections and bacteremia. Based upon multilocus sequence analysis, two subspecies and two genomosubspecies have been characterized for the species. We previously conducted whole-genome sequencing of 85 S. anginosus isolates from the urinary tract. Here, we present genomic analysis of this species, including isolates from the urinary tract as well as gut and fecal, vaginal, oral, respiratory, and blood and heart samples. Average nucleotide identity and core genome analysis revealed that these strains form two distinct groups. Group 1 is comprised of the S. anginosus type strain and other previously identified S. anginosus subspecies and genomosubspecies, including isolates from throughout the human body. In contrast, group 2 consists of predominantly urinary streptococci (n = 77; 85.6%). Both of these S. anginosus groups are distinct from other members of the Streptococcus anginosus group (SAG) species S. intermedius and S. constellatus. Genes conserved among all strains of one group but not in any strains in the other group were next identified. Group 1 strains included genes found in S. intermedius and S. constellatus, suggesting that they were lost within the ancestor of the group 2 strains. In contrast, genes unique to the group 2 strains were homologous to more distant streptococci, indicative of acquisition via horizontal gene transfer. These genes are ideal candidates for use as marker genes to distinguish between the two groups in the human microbiota. IMPORTANCE Whole-genome analysis of S. anginosus strains provides greater insight into the diversity of this species than from marker genes alone. Our investigation of 166 publicly available S. anginosus genomes via average nucleotide identity and core genome analysis revealed two phylogenomically distinct groups of this species, with one group almost exclusively consisting of isolates from the urinary tract. In contrast, only 8 urinary strains were identified within the other group, which contained the S. anginosus type strain, as well as all identified subspecies and genomosubspecies. While genomic analysis suggested that this urinary group of S. anginosus is genomically different from the previously characterized S. anginosus subspecies, phenotypic characterization is still needed. Given prior reports of the prevalence of S. anginosus in the urinary tract of both continent and incontinent females, future studies are needed to investigate if the symptom state of the urinary tract is associated with these two different groups.
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Affiliation(s)
- Ananya Prasad
- School of Biological Sciences, University of California San Diego, San Diego, California, USA
| | - Adriana Ene
- Bioinformatics Program, Loyola University Chicago, Chicago, Illinois, USA
| | - Sandra Jablonska
- Bioinformatics Program, Loyola University Chicago, Chicago, Illinois, USA
| | - Jingjie Du
- Department of Microbiology and Immunology, Loyola University Chicago, Maywood, Illinois, USA
| | - Alan J. Wolfe
- Department of Microbiology and Immunology, Loyola University Chicago, Maywood, Illinois, USA
| | - Catherine Putonti
- Bioinformatics Program, Loyola University Chicago, Chicago, Illinois, USA
- Department of Microbiology and Immunology, Loyola University Chicago, Maywood, Illinois, USA
- Department of Biology, Loyola University Chicago, Chicago, Illinois, USA
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Farias LABG, Firmino NN, Sousa MM, Lira ML, Meireles LN, Stolp ÂMV, Maia KM, Costa SF, Perdigão LV. Streptococcus constellatus causing concomitant extra and intracranial abscesses complicated with sagittal sinus thrombosis. Rev Inst Med Trop Sao Paulo 2023; 65:e10. [PMID: 36722672 PMCID: PMC9886223 DOI: 10.1590/s1678-9946202365010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Accepted: 12/13/2022] [Indexed: 02/02/2023] Open
Abstract
Streptococcus constellatus is a gram-positive coccus member of the Streptococcus anginosus group (SAG). It can be found in the oral flora, and may cause abscess more commonly in the gastrointestinal tract, lungs, and heart. Brain abscesses are severe neurological infections with high mortality rates. Streptococcus species other than S. pneumoniae are rare causes of brain abscesses. This case report highlights a severe case of extra and intracranial abscesses due to S. constellatus in an immunocompetent host.
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Affiliation(s)
- Luís Arthur Brasil Gadelha Farias
- Secretaria de Saúde do Estado, Programa de Residência Médica em Infectologia, Fortaleza, Ceará, Brazil,Hospital São José de Doenças Infecciosas, Fortaleza, Ceará, Brazil,Universidade de São Paulo, Faculdade de Medicina, São Paulo, São Paulo, Brazil
| | - Natália Nogueira Firmino
- Secretaria de Saúde do Estado, Programa de Residência Médica em Infectologia, Fortaleza, Ceará, Brazil,Hospital São José de Doenças Infecciosas, Fortaleza, Ceará, Brazil
| | - Marcos Maciel Sousa
- Secretaria de Saúde do Estado, Programa de Residência Médica em Infectologia, Fortaleza, Ceará, Brazil,Hospital São José de Doenças Infecciosas, Fortaleza, Ceará, Brazil
| | - Mateus Lavor Lira
- Secretaria de Saúde do Estado, Programa de Residência Médica em Infectologia, Fortaleza, Ceará, Brazil,Hospital São José de Doenças Infecciosas, Fortaleza, Ceará, Brazil
| | | | - Ângela Maria Veras Stolp
- Laboratório Central de Saúde Pública do Estado do Ceará, Fortaleza, Ceará, Brazil,Universidade de Fortaleza, Fortaleza, Ceará, Brazil
| | - Kelma Maria Maia
- Hospital São José de Doenças Infecciosas, Fortaleza, Ceará, Brazil
| | - Silvia Figueiredo Costa
- Universidade de São Paulo, Faculdade de Medicina, São Paulo, São Paulo, Brazil,Universidade de São Paulo, Faculdade de Medicina, Instituto de Medicina Tropical de São Paulo, São Paulo, São Paulo, Brazil
| | - Lauro Vieira Perdigão
- Hospital São José de Doenças Infecciosas, Fortaleza, Ceará, Brazil,Universidade de São Paulo, Faculdade de Medicina, São Paulo, São Paulo, Brazil
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13
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Widhani A, Djauzi S, Suyatna FD, Dewi BE. Changes in Gut Microbiota and Systemic Inflammation after Synbiotic Supplementation in Patients with Systemic Lupus Erythematosus: A Randomized, Double-Blind, Placebo-Controlled Trial. Cells 2022; 11:3419. [PMID: 36359816 PMCID: PMC9658918 DOI: 10.3390/cells11213419] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Revised: 10/22/2022] [Accepted: 10/23/2022] [Indexed: 08/04/2023] Open
Abstract
Gut dysbiosis has a role in the pathogenesis of lupus. Synbiotic supplementation may restore the balance of gut microbiota. This study investigated whether synbiotics could improve gut microbiota and systemic inflammation in lupus patients. This randomized, double-blind, placebo-controlled trial was conducted in adult systemic lupus erythematosus (SLE) patients. Subjects were randomized to receive either synbiotics or a placebo. Fecal microbiota, hs-CRP, IL-6, and IL-17 were measured at baseline and after 60 days. Patients who fulfilled the inclusion criteria were randomized into synbiotic (n = 23) and placebo groups (n = 23). In the synbiotic group, hs-CRP was not significantly increased (1.8 [0.9; 4.85] vs. 2.1 [0.9; 4.25] mg/L; pre vs. post; p = 0.23), whereas in the placebo group hs-CRP was increased significantly (1.75 [0.4; 4.45] vs. 3.75 [0.58; 7.05] mg/L; pre vs. post; p = 0.005). In the synbiotic group, IL-6 decreased significantly (8.76 [6.62; 11.39] vs. 6.59 [4.96; 8.01]; pre vs. post; p = 0.02), while there was no significant change in IL-17 level. In the placebo group, there was no significant change in IL-6 and IL-17. Synbiotic supplementation increased the Firmicutes:Bacteroidetes ratio (0.05 ± 0.60 vs. -0.08 ± 0.63, synbiotic vs. placebo p = 0.48) and butyrate metabolism (p = 0.037) and decreased amino sugar and nucleotide sugar metabolism (p = 0.040). There was improvement in the SLE disease activity index 2K (SLEDAI-2K) score in the synbiotic group (14 [9; 16] vs. 8 [2; 12]; pre vs. post; p < 0.001), while no change in the placebo group (9 [8; 18.25] vs. 9 [5.5; 15]; pre vs. post; p = 0.31). Synbiotic supplementation could reduce systemic inflammation and SLE disease activity and alter the composition and functions of gut microbiota.
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Affiliation(s)
- Alvina Widhani
- Allergy and Clinical Immunology Division, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia
- Dr. Cipto Mangunkusumo Hospital, Jakarta 10430, Indonesia
- Doctoral Program in Biomedical Science, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia
| | - Samsuridjal Djauzi
- Allergy and Clinical Immunology Division, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia
- Dr. Cipto Mangunkusumo Hospital, Jakarta 10430, Indonesia
| | | | - Beti Ernawati Dewi
- Department of Microbiology, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia
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14
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Kuryłek A, Stasiak M, Kern-Zdanowicz I. Virulence factors of Streptococcus anginosus - a molecular perspective. Front Microbiol 2022; 13:1025136. [PMID: 36386673 PMCID: PMC9643698 DOI: 10.3389/fmicb.2022.1025136] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Accepted: 10/10/2022] [Indexed: 07/21/2023] Open
Abstract
Streptococcus anginosus together with S. constellatus and S. intermedius constitute the Streptococcus anginosus group (SAG), until recently considered to be benign commensals of the human mucosa isolated predominantly from oral cavity, but also from upper respiratory, intestinal, and urogenital tracts. For years the virulence potential of SAG was underestimated, mainly due to complications in correct species identification and their assignment to the physiological microbiota. Still, SAG representatives have been associated with purulent infections at oral and non-oral sites resulting in abscesses formation and empyema. Also, life threatening blood infections caused by SAG have been reported. However, the understanding of SAG as potential pathogen is only fragmentary, albeit certain aspects of SAG infection seem sufficiently well described to deserve a systematic overview. In this review we summarize the current state of knowledge of the S. anginosus pathogenicity factors and their mechanisms of action.
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15
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Pilarczyk-Zurek M, Sitkiewicz I, Koziel J. The Clinical View on Streptococcus anginosus Group – Opportunistic Pathogens Coming Out of Hiding. Front Microbiol 2022; 13:956677. [PMID: 35898914 PMCID: PMC9309248 DOI: 10.3389/fmicb.2022.956677] [Citation(s) in RCA: 56] [Impact Index Per Article: 18.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Accepted: 06/17/2022] [Indexed: 11/13/2022] Open
Abstract
Three distinct streptococcal species: Streptococcus anginosus, Streptococcus intermedius, and Streptococcus constellatus, belonging to the Streptococcus anginosus group (SAG), also known as Streptococcus milleri group, have been attracting clinicians and microbiologists, not only as oral commensals but also as opportunistic pathogens. For years they have been simply classified as so called viridans streptococci, and distinct species were not associated with particular clinical manifestations. Therefore, description of SAG members are clearly underrepresented in the literature, compared to other medically relevant streptococci. However, the increasing number of reports of life-threatening infections caused by SAG indicates their emerging pathogenicity. The improved clinical data generated with the application of modern molecular diagnostic techniques allow for precise identification of individual species belonging to SAG. This review summarizes clinical reports on SAG infections and systematizes data on the occurrence of individual species at the site of infection. We also discuss the issue of proper microbiological diagnostics, which is crucial for further clinical treatment.
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Affiliation(s)
- Magdalena Pilarczyk-Zurek
- Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland
| | - Izabela Sitkiewicz
- Center for Translational Medicine, Warsaw University of Life Sciences (SGGW), Warszawa, Poland
| | - Joanna Koziel
- Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland
- *Correspondence: Joanna Koziel,
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16
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Jia J, Shi W, Dong F, Meng Q, Yuan L, Chen C, Yao K. Identification and molecular epidemiology of routinely determined Streptococcus pneumoniae with negative Quellung reaction results. J Clin Lab Anal 2022; 36:e24293. [PMID: 35170080 PMCID: PMC8993597 DOI: 10.1002/jcla.24293] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Revised: 01/08/2022] [Accepted: 01/24/2022] [Indexed: 11/16/2022] Open
Abstract
Background Some streptococci strains identified as Streptococcus pneumoniae (S. pneumoniae) by routine clinical methods exhibiting negative Quellung reaction results may belong to other species of viridans group streptococci or non‐typeable S. pneumoniae. The purpose of this study was to investigate the identification and molecular characteristics of S. pneumoniae with negative Quellung reaction results. Methods One hundred and five isolates identified as S. pneumoniae using routine microbiological methods with negative Quellung reaction results were included. Multilocus sequence analysis (MLSA) was used as a gold standard in species identification, and the capacity of matrix‐assisted laser desorption ionization‐time of flight mass spectrometry (MALDI‐TOF MS) in identification was evaluated. Capsular genes and sequence types of S. pneumoniae isolates were determined by sequential multiplex PCR and multilocus sequence typing. Antimicrobial susceptibility patterns were determined via broth microdilution with a commercialized 96‐well plate. Results Among the isolates, 81 were identified as S. pneumoniae and 24 were S. pseudopneumoniae by MLSA. MALDI‐TOF MS misidentified six S. pneumoniae isolates as S. pseudopneumoniae and nine S. pseudopneumoniae isolates as S. pneumoniae or S. mitis/S. oralis. Thirty‐one sequence types (STs) were detected for these 81 S. pneumoniae isolates, and the dominant ST was ST‐bj12 (16, 19.8%). The non‐susceptibility rates of S. pseudopneumoniae were comparable to those of NESp strains. Conclusions Some S. pneumoniae isolates identified by routine methods were S. pseudopneumoniae. Most NESp strains have a different genetic background compared with capsulated S. pneumoniae strains. The resistance patterns of S. pseudopneumoniae against common antibiotics were comparable to those of NESp.
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Affiliation(s)
- Ju Jia
- Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, National Key Discipline of Pediatrics (Capital Medical University), Beijing Pediatric Research Institute, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, Beijing, China
| | - Wei Shi
- Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, National Key Discipline of Pediatrics (Capital Medical University), Beijing Pediatric Research Institute, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, Beijing, China
| | - Fang Dong
- Clinical Laboratory, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, Beijing, China
| | - Qingying Meng
- Clinical Laboratory, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, Beijing, China
| | - Lin Yuan
- Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, National Key Discipline of Pediatrics (Capital Medical University), Beijing Pediatric Research Institute, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, Beijing, China
| | - Changhui Chen
- Department of Pediatrics, Youyang County People's Hospital, Chongqing, China
| | - Kaihu Yao
- Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, National Key Discipline of Pediatrics (Capital Medical University), Beijing Pediatric Research Institute, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, Beijing, China
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17
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Kwack KH, Lee JH, Moon JH. Whole genome and RNA sequencing of oral commensal bacterium Streptococcus anginosus subsp. anginosus with vancomycin tolerance. J Microbiol 2022; 60:167-176. [PMID: 34997538 DOI: 10.1007/s12275-022-1425-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Revised: 11/15/2021] [Accepted: 11/17/2021] [Indexed: 11/24/2022]
Abstract
"Antibiotic tolerance" promotes the rapid subsequent evolution of "antibiotic resistance," however, it is often overlooked because it is difficult to distinguish between tolerant and susceptible organisms. A commensal bacterium S. anginosus subsp. anginosus strain KHUD_S1, isolated from dental biofilm was found to exhibit a high MBC/MIC ratio of 32 against vancomycin. We observed KHUD_S1 cells exposed to vancomycin did not grow but maintained viability. Transmission electron microscope showed KHUD_S1 cells possessed a dense, thick capsule and maintained the cell wall integrity upon vancomycin exposure. To infer the underlying mechanisms of the vancomycin tolerance in KHUD_S1, we performed whole genome sequencing and RNA sequencing. The KHUD_S1 genome carried three genes encoding branching enzymes that can affect peptidoglycan structure through interpeptide bridge formation. Global gene expression profiling revealed that the vancomycin-induced downregulation of carbohydrate and inorganic ion transport/metabolism as well as translation is less prominent in KHUD_S1 than in the vancomycin susceptible strain KHUD_S3. Based on the transcriptional levels of genes related to peptidoglycan synthesis, KHUD_S1 was determined to have a 3D peptidoglycan architecture distinct from KHUD_S3. It was found that, under vancomycin exposure, the peptidoglycan was remodeled through changes in the interpeptide bridge and transpeptidation reactions. Collectively, these features of S. anginosus KHUD_S1, including a dense capsule and differential gene expression in peptidoglycan synthesis, may contribute to vancomycin tolerance. Our results showing the occurrence of vancomycin tolerance amongst oral commensal bacteria highlight the need for considering future strategies for screening of antibiotic tolerance as an effort to reduce antibiotic resistance.
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Affiliation(s)
- Kyu Hwan Kwack
- Department of Dentistry, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea
- Present address: Department of Oral Biology, University at Buffalo School of Dental Medicine, Buffalo, New York, 14214, USA
| | - Jae-Hyung Lee
- Department of Oral Microbiology, School of Dentistry, Kyung Hee University, Seoul, 02447, Republic of Korea.
| | - Ji-Hoi Moon
- Department of Oral Microbiology, School of Dentistry, Kyung Hee University, Seoul, 02447, Republic of Korea.
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18
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Lemaire C, Le Gallou B, Lanotte P, Mereghetti L, Pastuszka A. Distribution, Diversity and Roles of CRISPR-Cas Systems in Human and Animal Pathogenic Streptococci. Front Microbiol 2022; 13:828031. [PMID: 35173702 PMCID: PMC8841824 DOI: 10.3389/fmicb.2022.828031] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Accepted: 01/10/2022] [Indexed: 12/26/2022] Open
Abstract
Streptococci form a wide group of bacteria and are involved in both human and animal pathologies. Among pathogenic isolates, differences have been highlighted especially concerning their adaptation and virulence profiles. CRISPR-Cas systems have been identified in bacteria and many streptococci harbor one or more systems, particularly subtypes I-C, II-A, and III-A. Since the demonstration that CRISPR-Cas act as an adaptive immune system in Streptococcus thermophilus, a lactic bacteria, the diversity and role of CRISPR-Cas were extended to many germs and functions were enlarged. Among those, the genome editing tool based on the properties of Cas endonucleases is used worldwide, and the recent attribution of the Nobel Prize illustrates the importance of this tool in the scientific world. Another application is CRISPR loci analysis, which allows to easily characterize isolates in order to understand the interactions of bacteria with their environment and visualize species evolution. In this review, we focused on the distribution, diversity and roles of CRISPR-Cas systems in the main pathogenic streptococci.
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Affiliation(s)
- Coralie Lemaire
- Université de Tours, INRAE, Infectiologie et Santé Publique, BRMF, Tours, France
- Service de Bactériologie-Virologie, Centre Hospitalier Régional Universitaire de Tours, Tours, France
| | - Brice Le Gallou
- Université de Tours, INRAE, Infectiologie et Santé Publique, BRMF, Tours, France
- Service de Bactériologie-Virologie, Centre Hospitalier Régional Universitaire de Tours, Tours, France
| | - Philippe Lanotte
- Université de Tours, INRAE, Infectiologie et Santé Publique, BRMF, Tours, France
- Service de Bactériologie-Virologie, Centre Hospitalier Régional Universitaire de Tours, Tours, France
- *Correspondence: Philippe Lanotte,
| | - Laurent Mereghetti
- Université de Tours, INRAE, Infectiologie et Santé Publique, BRMF, Tours, France
- Service de Bactériologie-Virologie, Centre Hospitalier Régional Universitaire de Tours, Tours, France
| | - Adeline Pastuszka
- Université de Tours, INRAE, Infectiologie et Santé Publique, BRMF, Tours, France
- Service de Bactériologie-Virologie, Centre Hospitalier Régional Universitaire de Tours, Tours, France
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Esmail GA, Al-Dhabi NA, AlDawood B, Somily AM. Shotgun whole genome sequencing of drug-resistance Streptococcus anginosus strain 47S1 isolated from a patient with pharyngitis in Saudi Arabia. J Infect Public Health 2021; 14:1740-1749. [PMID: 34836797 DOI: 10.1016/j.jiph.2021.11.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2021] [Revised: 11/03/2021] [Accepted: 11/09/2021] [Indexed: 10/19/2022] Open
Abstract
BACKGROUND Streptococcus anginosus is an emergence opportunistic pathogen that colonize the human upper respiratory tract (URT), S. anginosus alongside with S. intermedius and S. constellatus, members of S. anginosus group, are implicated in several human infections. However, our understanding this bacterium to the genotype level with determining the genes associated with pathogenicity and antimicrobial resistance (AMR) is scarce. S. anginosus 47S1 strain was isolated from sore throat infection, the whole genome was characterized and the virulence & AMR genes contributing in pathogenicity were investigated. METHODOLOGY The whole genome of 47S1 was sequenced by Illumina sequencing technology. Strain 47S1 genome was de novo assembled with different strategies and annotated via PGAP, PROKKA and RAST pipelines. Identifying the CRISPR-Cass system and prophages sequences was performed using CRISPRloci and PhiSpy tools respectively. Prediction the virulence genes were performed with the VFDB database. AMR genes were detected in silico using NCBI AMRFinderPlus pipeline and CARD database and compared with in vitro AST findings. RESULTS β-hemolytic strain 47S1 was identified with conventional microbiology techniques and confirmed by the sequences of 16S rRNA gene. Genome of 47S1 comprised of 1981512 bp. Type I-C CRISPR-Cas system and 4 prophages were detected among the genome of 47S1. Several virulence genes were predicted, most of these genes are found in other pathogenic streptococci, mainly lmb, pavA, htrA/degP, eno, sagA, psaA and cpsI which play a significant role in colonizing, invading host tissues and evade form immune system. In silico AMR findings showed that 47S1 gnome harbors (tetA, tetB &tet32), (aac(6')-I, aadK &aph(3')-IVa), fusC, and PmrA genes that mediated-resistance to tetracyclines, aminoglycosides, fusidic acid, and fluoroquinolone respectively which corresponds with in vitro AST obtained results. In conclusion, WGS is a key approach to predict the virulence and AMR genes, results obtained in this study may contribute for a better understanding of the opportunistic S. anginosus pathogenicity.
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Affiliation(s)
- Galal Ali Esmail
- Department of Botany and Microbiology, College of Sciences, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
| | - Naif Abdullah Al-Dhabi
- Department of Botany and Microbiology, College of Sciences, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
| | - Badr AlDawood
- Department of Emergency Medicine, College of Medicine, King Saud University, King Saud University Medical City, Riyadh 11461, Saudi Arabia
| | - Ali Mohammed Somily
- Department of Pathology and Laboratory Medicine/Microbiology, College of Medicine, King Saud University, King Saud University Medical City, Riyadh 11461, Saudi Arabia.
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Chang KM, Hsieh SL, Koshy R. An Unusual Case of Streptococcus anginosus Endocarditis in a Healthy Host With Bicuspid Aortic Valve. Cureus 2021; 13:e13171. [PMID: 33692930 PMCID: PMC7938714 DOI: 10.7759/cureus.13171] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Streptococcus anginosus group (SAG) is a subgroup of viridans streptococci and can be found ubiquitously in normal human flora. SAG is known to form invasive pyogenic infection when it becomes pathogenic. Yet, SAG is a very rare cause of endocarditis, and there is a dearth of case reports on this topic. We present a rare case of native bicuspid aortic valve endocarditis secondary to S. anginosus that caused aortic insufficiency and ascending aortic aneurysm. To our knowledge, this is the first well-documented case report of community-acquired S. anginosus endocarditis on a bicuspid aortic valve in an immunocompetent patient. The patient first presented with cough that was likely due to bronchus irritation from a 5.5 x 5.2 cm ascending aortic aneurysm. He underwent aortic valve replacement with bovine bioprosthesis and ascending aortic aneurysm repairment and was treated with a two-week regimen of IV ceftriaxone and gentamicin followed by another four weeks of IV ceftriaxone. He was eventually discharged to a rehabilitation facility. SAG is usually susceptible to beta-lactam antibiotics. The prognosis of SAG infection is usually good, but progression to bacteremia carries a poor outcome.
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Affiliation(s)
- Kai-Ming Chang
- Division of Infectious Diseases, Department of Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Health, Manhasset, USA
| | - Sharon L Hsieh
- Internal Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA
| | - Robin Koshy
- Division of Infectious Diseases, Department of Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Health, Manhasset, USA
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21
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Zhou Z, Charlesworth J, Achtman M. Accurate reconstruction of bacterial pan- and core genomes with PEPPAN. Genome Res 2020; 30:1667-1679. [PMID: 33055096 PMCID: PMC7605250 DOI: 10.1101/gr.260828.120] [Citation(s) in RCA: 62] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Accepted: 09/01/2020] [Indexed: 12/22/2022]
Abstract
Bacterial genomes can contain traces of a complex evolutionary history, including extensive homologous recombination, gene loss, gene duplications, and horizontal gene transfer. To reconstruct the phylogenetic and population history of a set of multiple bacteria, it is necessary to examine their pangenome, the composite of all the genes in the set. Here we introduce PEPPAN, a novel pipeline that can reliably construct pangenomes from thousands of genetically diverse bacterial genomes that represent the diversity of an entire genus. PEPPAN outperforms existing pangenome methods by providing consistent gene and pseudogene annotations extended by similarity-based gene predictions, and identifying and excluding paralogs by combining tree- and synteny-based approaches. The PEPPAN package additionally includes PEPPAN_parser, which implements additional downstream analyses, including the calculation of trees based on accessory gene content or allelic differences between core genes. To test the accuracy of PEPPAN, we implemented SimPan, a novel pipeline for simulating the evolution of bacterial pangenomes. We compared the accuracy and speed of PEPPAN with four state-of-the-art pangenome pipelines using both empirical and simulated data sets. PEPPAN was more accurate and more specific than any of the other pipelines and was almost as fast as any of them. As a case study, we used PEPPAN to construct a pangenome of approximately 40,000 genes from 3052 representative genomes spanning at least 80 species of Streptococcus The resulting gene and allelic trees provide an unprecedented overview of the genomic diversity of the entire Streptococcus genus.
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Affiliation(s)
- Zhemin Zhou
- Warwick Medical School, University of Warwick, Coventry CV4 7AL, United Kingdom
| | - Jane Charlesworth
- Warwick Medical School, University of Warwick, Coventry CV4 7AL, United Kingdom
| | - Mark Achtman
- Warwick Medical School, University of Warwick, Coventry CV4 7AL, United Kingdom
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22
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Mora-Palma JC, Guillot-Suay V, Sánchez Gila MM, Gutiérrez-Fernández J. [Pelvic inflammatory disease by Streptococcus constellatus. Clinical experience and a review]. REVISTA ESPANOLA DE QUIMIOTERAPIA : PUBLICACION OFICIAL DE LA SOCIEDAD ESPANOLA DE QUIMIOTERAPIA 2020; 33:285-288. [PMID: 32515179 PMCID: PMC7374034 DOI: 10.37201/req/020.2020] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/21/2020] [Revised: 04/03/2020] [Accepted: 04/14/2020] [Indexed: 06/11/2023]
Affiliation(s)
| | | | | | - J Gutiérrez-Fernández
- José Gutiérrez-Fernández. Servicio de Microbiología. Hospital Universitario Virgen de las Nieves. Avenida de las Fuerzas Armadas, 2. E-18012 Granada, Spain.
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23
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Draft Genome Sequence of Streptococcus anginosus UMB1296, Isolated from the Female Urinary Tract. Microbiol Resour Announc 2020; 9:9/20/e00409-20. [PMID: 32409556 PMCID: PMC7225555 DOI: 10.1128/mra.00409-20] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/04/2022] Open
Abstract
We present the draft genome sequence of a Streptococcus anginosus strain isolated from the female urinary tract. The S. anginosus UMB1296 draft genome has a size of 1,924,009 bp assembled into 35 contigs with a GC content of 38.69%. Genome annotation revealed 1,775 protein-coding genes, including several known virulence factors. We present the draft genome sequence of a Streptococcus anginosus strain isolated from the female urinary tract. The S. anginosus UMB1296 draft genome has a size of 1,924,009 bp assembled into 35 contigs with a GC content of 38.69%. Genome annotation revealed 1,775 protein-coding genes, including several known virulence factors.
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24
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Issa E, Salloum T, Tokajian S. From Normal Flora to Brain Abscesses: A Review of Streptococcus intermedius. Front Microbiol 2020; 11:826. [PMID: 32457718 PMCID: PMC7221147 DOI: 10.3389/fmicb.2020.00826] [Citation(s) in RCA: 64] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2020] [Accepted: 04/07/2020] [Indexed: 11/13/2022] Open
Abstract
Streptococcus intermedius is a β-hemolytic Gram-positive member of the Streptococcus anginosus group (SAG). Despite being a part of the normal microbiota, it is one of the most common pathogens associated with brain and liver abscesses and thoracic empyema, increasing as a result the morbidity and mortality rates in affected patients. Though there are numerous published case reports on S. intermedius infections, it is still understudied compared to other SAG members. Our knowledge of the genomic factors contributing to its dissemination to the brain and abscess development is also limited to few characterized genes. In this review, we summarize our current knowledge on S. intermedius identification methods, virulence factors, and insight provided by the whole-genome and correlate patients’ metadata, symptoms, and disease outcome with S. intermedius infections in 101 recent case reports obtained from PubMed. This combined information highlights the gaps in our understanding of S. intermedius pathogenesis, suggesting future research directions to unveil the factors contributing to abscess development.
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Affiliation(s)
- Elio Issa
- Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Byblos, Lebanon
| | - Tamara Salloum
- Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Byblos, Lebanon
| | - Sima Tokajian
- Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Byblos, Lebanon
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25
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Bauer R, Neffgen N, Grempels A, Furitsch M, Mauerer S, Barbaqadze S, Haase G, Kestler H, Spellerberg B. Heterogeneity of Streptococcus anginosus ß-hemolysis in relation to CRISPR/Cas. Mol Oral Microbiol 2020; 35:56-65. [PMID: 31977149 DOI: 10.1111/omi.12278] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2019] [Revised: 01/13/2020] [Accepted: 01/17/2020] [Indexed: 11/28/2022]
Abstract
Streptococcus anginosus is a commensal of the oral mucosa that can cause severe invasive infections. A considerable proportion of Streptococcus anginosus strains are ß-hemolytic due to the presence of an SLS-like gene cluster. However, the majority of strains do not display ß-hemolysis. To investigate ß-hemolysin heterogeneity in S. anginosus, we determined the presence of sag genes and correlated it with the presence of CRISPR/Cas genes in a collection of ß-hemolytic and non-ß-hemolytic strains. All of the ß-hemolytic strains carried the sag gene cluster. In contrast to other streptococci, clinical S. anginosus strains that do not display ß-hemolysis do not harbor sag genes. Phylogenetic analysis of the ß-hemolytic strains revealed that they belong to two previously defined clusters within S. anginosus. Correlation with CRISPR/Cas genes showed a significant difference for the presence of CRISPR/Cas in ß-hemolytic versus non-ß-hemolytic isolates. The presence of the CRISPR/Cas type IIA or type IIC locus is associated with the absence of sag genes; in 65% of the non-ß-hemolytic strains a CRISPR/Cas locus was found, while only 24% of ß-hemolytic strains carry CRISPR/Cas genes. Further analysis of the spacer content of the CRISPR systems revealed the presence of multiple self-targeting sequences directed against S. anginosus genes. These results support the hypothesis that horizontal gene transfer is involved in the acquisition of ß-hemolysin genes and that CRISPR/Cas may limit DNA uptake in S. anginosus.
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Affiliation(s)
- Richard Bauer
- Institute of Medical Microbiology and Hospital Hygiene, University of Ulm, Ulm, Germany
| | - Nathalie Neffgen
- Institute of Medical Microbiology and Hospital Hygiene, University of Ulm, Ulm, Germany
| | - Aline Grempels
- Institute of Medical Microbiology and Hospital Hygiene, University of Ulm, Ulm, Germany
| | - Martina Furitsch
- Institute of Medical Microbiology and Hospital Hygiene, University of Ulm, Ulm, Germany
| | - Stefanie Mauerer
- Institute of Medical Microbiology and Hospital Hygiene, University of Ulm, Ulm, Germany
| | - Salome Barbaqadze
- General Microbiology Lab, Eliava Bacteriophage, Microbiology and Virology Institute, Tbilisi, Georgia
| | - Gerhard Haase
- LDZ Microbiology, RWTH Aachen University Hospital, Aachen, Germany
| | - Hans Kestler
- Institute of Medical Systems Biology, Ulm University, Ulm, Germany
| | - Barbara Spellerberg
- Institute of Medical Microbiology and Hospital Hygiene, University of Ulm, Ulm, Germany
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26
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O. Luiz FBD, Alves KB, Barros RR. Prevalence and long-term persistence of beta-haemolytic streptococci throat carriage among children and young adults. J Med Microbiol 2019; 68:1526-1533. [DOI: 10.1099/jmm.0.001054] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Affiliation(s)
- Fernanda Baptista de O. Luiz
- Departamento Microbiologia e Parasitologia, Instituto Biomédico, Universidade Federal Fluminense, Rua Professor Ernani de Melo 101, Niterói, RJ, 24210-130, Brazil
| | - Karen B. Alves
- Departamento Microbiologia e Parasitologia, Instituto Biomédico, Universidade Federal Fluminense, Rua Professor Ernani de Melo 101, Niterói, RJ, 24210-130, Brazil
| | - Rosana R. Barros
- Departamento Microbiologia e Parasitologia, Instituto Biomédico, Universidade Federal Fluminense, Rua Professor Ernani de Melo 101, Niterói, RJ, 24210-130, Brazil
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27
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Tabata A, Yamada T, Ohtani H, Ohkura K, Tomoyasu T, Nagamune H. β-Hemolytic Streptococcus anginosus subsp. anginosus causes streptolysin S-dependent cytotoxicity to human cell culture lines in vitro. J Oral Microbiol 2019; 11:1609839. [PMID: 31105901 PMCID: PMC6508071 DOI: 10.1080/20002297.2019.1609839] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Revised: 04/09/2019] [Accepted: 04/12/2019] [Indexed: 11/30/2022] Open
Abstract
Background: Streptococcus anginosus subsp. anginosus (SAA) is one of the opportunistic pathogens in humans that inhabits the oral cavity. The type strain of SAA, NCTC10713T, showed clear β-hemolysis on blood agar plates, and the sole β-hemolytic factor revealed two streptolysin S (SLS) molecules. SLS is well known as the peptide hemolysin produced from the human pathogen S. pyogenes and shows not only hemolytic activity on erythrocytes but also cytotoxic activity in cell culture lines in vitro and in vivo, such as in a mouse infection model. However, no cytotoxic activity of SLS produced from β-hemolytic SAA (β-SAA) has been reported so far. Objective and Design: In this study, the SLS-dependent cytotoxicity of the β-SAA strains including the genetically modified strains was investigated in vitro. Results: The SLS-producing β-SAA showed cytotoxicity in human cell culture lines under the co-cultivation condition and it was found that this cytotoxicity was caused by the SLS secreted into the extracellular milieu. Conclusion: The results from this study suggest that the SLS produced from β-SAA might indicate the cytotoxic potential similar to that of the SLS from S. pyogenes and the SLS-producing β-SAA would be recognized as “a wolf in sheep’s clothing” More attention will be paid to the pathogenicity of β-hemolytic Anginosus group streptococci.
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Affiliation(s)
- Atsushi Tabata
- Department of Bioengineering, Division of Bioscience and Bioindustry, Graduate School of Technology, Industrial and Social Sciences, Tokushima University Graduate School, Tokushima, Japan.,Department of Biological Science and Technology, Life System, Institute of Technology and Science, Tokushima University Graduate School, Tokushima, Japan
| | - Takuya Yamada
- Department of Biological Science and Technology, Life System, Institute of Technology and Science, Tokushima University Graduate School, Tokushima, Japan
| | - Hiromi Ohtani
- Department of Biological Science and Technology, Life System, Institute of Technology and Science, Tokushima University Graduate School, Tokushima, Japan
| | - Kazuto Ohkura
- Graduate School of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Japan
| | - Toshifumi Tomoyasu
- Department of Bioengineering, Division of Bioscience and Bioindustry, Graduate School of Technology, Industrial and Social Sciences, Tokushima University Graduate School, Tokushima, Japan.,Department of Biological Science and Technology, Life System, Institute of Technology and Science, Tokushima University Graduate School, Tokushima, Japan
| | - Hideaki Nagamune
- Department of Bioengineering, Division of Bioscience and Bioindustry, Graduate School of Technology, Industrial and Social Sciences, Tokushima University Graduate School, Tokushima, Japan.,Department of Biological Science and Technology, Life System, Institute of Technology and Science, Tokushima University Graduate School, Tokushima, Japan
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28
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Issa E, Salloum T, Panossian B, Ayoub D, Abboud E, Tokajian S. Genome Mining and Comparative Analysis of Streptococcus intermedius Causing Brain Abscess in a Child. Pathogens 2019; 8:pathogens8010022. [PMID: 30781742 PMCID: PMC6471051 DOI: 10.3390/pathogens8010022] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Revised: 01/18/2019] [Accepted: 01/30/2019] [Indexed: 01/09/2023] Open
Abstract
Streptococcus intermedius (SI) is associated with prolonged hospitalization and low survival rates. The genetic mechanisms involved in brain abscess development and genome evolution in comparison to other members of the Streptococcus anginosus group are understudied. We performed a whole-genome comparative analysis of an SI isolate, LAU_SINT, associated with brain abscess following sinusitis with all SI genomes in addition to S. constellatus and S. anginosus. Selective pressure on virulence factors, phages, pan-genome evolution and single-nucleotide polymorphism analysis were assessed. The structural details of the type seven secretion system (T7SS) was elucidated and compared with different organisms. ily and nanA were both abundant and conserved. Nisin resistance determinants were found in 47% of the isolates. Pan-genome and SNPs-based analysis didn’t reveal significant geo-patterns. Our results showed that two SC isolates were misidentified as SI. We propose the presence of four T7SS modules (I–IV) located on various genomic islands. We detected a variety of factors linked to metal ions binding on the GIs carrying T7SS. This is the first detailed report characterizing the T7SS and its link to nisin resistance and metal ions binding in SI. These and yet uncharacterized T7SS transmembrane proteins merit further studies and could represent potential therapeutic targets.
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Affiliation(s)
- Elio Issa
- Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Byblos 36, Lebanon.
| | - Tamara Salloum
- Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Byblos 36, Lebanon.
| | - Balig Panossian
- Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Byblos 36, Lebanon.
| | - David Ayoub
- Department of Neurosurgery, the Middle East Institute of Health University Hospital, Beirut 60-387, Lebanon.
| | - Edmond Abboud
- Laboratory Department, the Middle East Institute of Health University Hospital, Beirut 60-387, Lebanon.
| | - Sima Tokajian
- Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Byblos 36, Lebanon.
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29
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Tomoyasu T, Matoba M, Takao A, Tabata A, Whiley RA, Maeda N, Nagamune H. Rapid screening method for detecting highly pathogenic Streptococcus intermedius strains carrying a mutation in the lacR gene. FEMS Microbiol Lett 2018; 365:4705894. [PMID: 29228148 DOI: 10.1093/femsle/fnx258] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2017] [Accepted: 11/30/2017] [Indexed: 11/12/2022] Open
Abstract
Streptococcus intermedius is a member of the normal human commensal flora and secretes a human-specific cytolysin intermedilysin (ILY) as a major virulence factor. Expression of ily is repressed by LacR and loss-of-function mutations of LacR are observed in many ILY high-producing strains isolated from deep-seated abscesses, suggesting that high ILY production is necessary for increased virulence. However, because ILY exhibits no β-hemolysis on animal blood agar plates, differentiating ILY high- and low-producing strains using conventional laboratory methods is not possible. Interestingly, S. intermedius also produces glycosidases, including MsgA and NanA, which exhibit N-acetyl-β-d-glucosaminidase and neuraminidase activities, respectively. Moreover, MsgA expression, but not NanA, is negatively regulated by LacR. Here we measured the activities of MsgA, NanA and ILY in strains isolated from clinical specimens and dental plaque to determine the correlation between these glycosidase activities and ILY hemolytic activity. Hemolytic activity showed a strong positive correlation with MsgA and a weak negative correlation with NanA activities. Therefore, we calculated the ratio of MsgA and NanA activity (M/N ratio). This value showed a stronger positive correlation (r = 0.81) with ILY hemolytic activity and many strains with high M/N ratios (>2) were ILY-high producers with loss-of-function mutations in LacR.
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Affiliation(s)
- Toshifumi Tomoyasu
- Field of Biomolecular Functions and Technology, Department of Bioscience and Bioindustry, Graduate School of Bioscience and Bioindustry, Tokushima University Graduate School, Minami-josanjima-cho, Tokushima 770-8513, Japan.,Department of Resource Circulation Engineering, Center for Frontier Research of Engineering, Tokushima University Graduate School, Minami-josanjima-cho, Tokushima 770-8506, Japan.,Department of Biological Science and Technology, Institute of Technology and Science, Tokushima University Graduate School, Minami-josanjima-cho, Tokushima 770-8506, Japan
| | - Masaki Matoba
- Department of Biological Science and Technology, Institute of Technology and Science, Tokushima University Graduate School, Minami-josanjima-cho, Tokushima 770-8506, Japan
| | - Ayuko Takao
- Department of Oral Microbiology, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku 230-8501, Japan
| | - Atsushi Tabata
- Field of Biomolecular Functions and Technology, Department of Bioscience and Bioindustry, Graduate School of Bioscience and Bioindustry, Tokushima University Graduate School, Minami-josanjima-cho, Tokushima 770-8513, Japan.,Department of Biological Science and Technology, Institute of Technology and Science, Tokushima University Graduate School, Minami-josanjima-cho, Tokushima 770-8506, Japan
| | - Robert A Whiley
- Department of Clinical and Diagnostic Oral Sciences, Institute of Dentistry, Bart's and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London E1 2AT, UK
| | - Nobuko Maeda
- Department of Oral Microbiology, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku 230-8501, Japan
| | - Hideaki Nagamune
- Field of Biomolecular Functions and Technology, Department of Bioscience and Bioindustry, Graduate School of Bioscience and Bioindustry, Tokushima University Graduate School, Minami-josanjima-cho, Tokushima 770-8513, Japan.,Department of Biological Science and Technology, Institute of Technology and Science, Tokushima University Graduate School, Minami-josanjima-cho, Tokushima 770-8506, Japan
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30
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A novel plasmid, pSAA0430-08, from Streptococcus anginosus subsp. anginosus strain 0430-08. Plasmid 2018; 95:16-27. [DOI: 10.1016/j.plasmid.2018.01.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2017] [Revised: 01/02/2018] [Accepted: 01/11/2018] [Indexed: 11/21/2022]
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31
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Development of a multiplex PCR for identification of β-hemolytic streptococci relevant to human infections and serotype distribution of invasive Streptococcus agalactiae in Thailand. Mol Cell Probes 2017; 36:10-14. [DOI: 10.1016/j.mcp.2017.06.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2017] [Revised: 06/07/2017] [Accepted: 06/26/2017] [Indexed: 11/23/2022]
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32
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Hatrongjit R, Akeda Y, Hamada S, Gottschalk M, Kerdsin A. Multiplex PCR for identification of six clinically relevant streptococci. J Med Microbiol 2017; 66:1590-1595. [DOI: 10.1099/jmm.0.000615] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Affiliation(s)
- Rujirat Hatrongjit
- Faculty of Science and Engineering, Kasetsart University Chalermphrakiat Sakon Nakhon Province Campus, Sakon Nakhon, Thailand
| | - Yukihiro Akeda
- Osaka University Hospital, Osaka University, Osaka, Japan
| | - Shigeyuki Hamada
- Thailand-Japan Research Collaboration Center for Emerging and Re-emerging Infections, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
| | | | - Anusak Kerdsin
- Faculty of Public Health, Kasetsart University Chalermphrakiat Sakon Nakhon Province Campus, Sakon Nakhon, Thailand
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33
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Positive- and Negative-Control Pathways by Blood Components for Intermedilysin Production in Streptococcus intermedius. Infect Immun 2017; 85:IAI.00379-17. [PMID: 28607101 DOI: 10.1128/iai.00379-17] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2017] [Accepted: 06/08/2017] [Indexed: 11/20/2022] Open
Abstract
Streptococcus intermedius is an opportunistic bacterial pathogen secreting a human-specific cytolysin called intermedilysin (ILY) as a major pathogenic factor. This bacterium can degrade glycans into monosaccharides using two glycosidases, multisubstrate glycosidase A (MsgA) and neuraminidase (NanA). Here, we detected a stronger hemolytic activity mediated by ILY when S. intermedius PC574 was cultured in fetal bovine serum (FBS) than when it was grown in the standard culture medium. FBS-cultured cells also showed higher MsgA and NanA activity, although overproduction of ILY in FBS was undetectable in mutants nanA-null and msgA-null. Addition of purified MsgA and NanA to the FBS resulted in a release of 2.8 mM galactose and 4.3 mM N-acetylneuraminic acid; these sugar concentrations were sufficient to upregulate the expression of ILY, MsgA, and NanA. Conversely, when strain PC574 was cultured in human plasma, no similar increase in hemolytic activity was observed. Moreover, addition of human plasma to the culture in FBS appeared to inhibit the stimulatory effect of FBS on ILY, MsgA, and NanA, although there were individual differences among the plasma samples. We confirmed that human plasma contains immunoglobulins that can neutralize ILY, MsgA, and NanA activities. In addition, human plasma had a neutralizing effect on cytotoxicity of S. intermedius toward HepG2 cells in FBS, and a higher concentration of human plasma was necessary to reduce the cytotoxicity of an ILY-high-producing strain than an ILY-low-producing strain. Overall, our data show that blood contains factors that stimulate and inhibit ILY expression and activity, which may affect pathogenicity of S. intermedius.
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34
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Members of a new subgroup of Streptococcus anginosus harbor virulence related genes previously observed in Streptococcus pyogenes. Int J Med Microbiol 2017; 307:174-181. [DOI: 10.1016/j.ijmm.2017.02.002] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2016] [Revised: 12/15/2016] [Accepted: 02/24/2017] [Indexed: 11/22/2022] Open
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35
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Mendonca ML, Szamosi JC, Lacroix AM, Fontes ME, Bowdish DM, Surette MG. The sil Locus in Streptococcus Anginosus Group: Interspecies Competition and a Hotspot of Genetic Diversity. Front Microbiol 2017; 7:2156. [PMID: 28119678 PMCID: PMC5222867 DOI: 10.3389/fmicb.2016.02156] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2016] [Accepted: 12/21/2016] [Indexed: 01/09/2023] Open
Abstract
The Streptococcus Invasion Locus (Sil) was first described in Streptococcus pyogenes and Streptococcus pneumoniae, where it has been implicated in virulence. The two-component peptide signaling system consists of the SilA response regulator and SilB histidine kinase along with the SilCR signaling peptide and SilD/E export/processing proteins. The presence of an associated bacteriocin region suggests this system may play a role in competitive interactions with other microbes. Comparative analysis of 42 Streptococcus Anginosus/Milleri Group (SAG) genomes reveals this to be a hot spot for genomic variability. A cluster of bacteriocin/immunity genes is found adjacent to the sil system in most SAG isolates (typically 6–10 per strain). In addition, there were two distinct SilCR peptides identified in this group, denoted here as SilCRSAG-A and SilCRSAG-B, with corresponding alleles in silB. Our analysis of the 42 sil loci showed that SilCRSAG-A is only found in Streptococcus intermedius while all three species can carry SilCRSAG-B. In S. intermedius B196, a putative SilA operator is located upstream of bacteriocin gene clusters, implicating the sil system in regulation of microbe–microbe interactions at mucosal surfaces where the group resides. We demonstrate that S. intermedius B196 responds to its cognate SilCRSAG-A, and, less effectively, to SilCRSAG-B released by other Anginosus group members, to produce putative bacteriocins and inhibit the growth of a sensitive strain of S. constellatus.
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Affiliation(s)
- Michelle L Mendonca
- Department of Biochemistry and Biomedical Sciences, McMaster University, HamiltonON, Canada; Farncombe Family Digestive Health Research Institute, McMaster University, HamiltonON, Canada
| | - Jake C Szamosi
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton ON, Canada
| | - Anne-Marie Lacroix
- Department of Biochemistry and Biomedical Sciences, McMaster University, HamiltonON, Canada; Farncombe Family Digestive Health Research Institute, McMaster University, HamiltonON, Canada
| | - Michelle E Fontes
- Department of Biochemistry and Biomedical Sciences, McMaster University, HamiltonON, Canada; Farncombe Family Digestive Health Research Institute, McMaster University, HamiltonON, Canada
| | - Dawn M Bowdish
- Department of Pathology and Molecular Medicine, McMaster University, HamiltonON, Canada; Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, HamiltonON, Canada
| | - Michael G Surette
- Department of Biochemistry and Biomedical Sciences, McMaster University, HamiltonON, Canada; Farncombe Family Digestive Health Research Institute, McMaster University, HamiltonON, Canada; Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, HamiltonON, Canada; Department of Medicine, McMaster University, HamiltonON, Canada
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Munson E, Carroll KC. What's in a Name? New Bacterial Species and Changes to Taxonomic Status from 2012 through 2015. J Clin Microbiol 2017; 55:24-42. [PMID: 27795334 PMCID: PMC5228236 DOI: 10.1128/jcm.01379-16] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
Technological advancements in fields such as molecular genetics and the human microbiome have resulted in an unprecedented recognition of new bacterial genus/species designations by the International Journal of Systematic and Evolutionary Microbiology Knowledge of designations involving clinically significant bacterial species would benefit clinical microbiologists in the context of emerging pathogens, performance of accurate organism identification, and antimicrobial susceptibility testing. In anticipation of subsequent taxonomic changes being compiled by the Journal of Clinical Microbiology on a biannual basis, this compendium summarizes novel species and taxonomic revisions specific to bacteria derived from human clinical specimens from the calendar years 2012 through 2015.
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Affiliation(s)
- Erik Munson
- College of Health Sciences, Marquette University, Milwaukee, Wisconsin, USA
| | - Karen C Carroll
- Division of Medical Microbiology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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Rahman M, Nguyen SV, McCullor KA, King CJ, Jorgensen JH, McShan WM. Comparative Genome Analysis of the Daptomycin-Resistant Streptococcus anginosus Strain J4206 Associated with Breakthrough Bacteremia. Genome Biol Evol 2016; 8:3446-3459. [PMID: 27678123 PMCID: PMC5203781 DOI: 10.1093/gbe/evw241] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Streptococcus anginosus is a member of the normal oral flora that can become a pathogen causing pyogenic infections in humans. The genome of daptomycin-resistant strain J4206, originally isolated from a patient suffering from breakthrough bacteremia and septic shock at the University of Texas Health Science Center at San Antonio, was determined. The circular genome is 2,001,352 bp long with a GC content of 38.62% and contains multiple mobile genetic elements, including the phage-like chromosomal island SanCI that mediates a mutator phenotype, transposons, and integrative conjugative elements. Daptomycin resistance involves multiple alterations in the cell membrane and cell wall, and unique features were identified in J4206 that may contribute to resistance. A cluster of capsular polysaccharide (CPS) genes for choline metabolism and transport are present that may help neutralize cell surface charges, destabilizing daptomycin binding. Further, unique J4206 genes encoding sortases and LPXTG-target proteins that are involved in cell wall modification were present. The J4206 genome is phylogenetically closely related to the recently reported vancomycin-resistant SA1 strain; however, these genomes differ with SNPs in cardiolipin synthetase, histidine kinase yycG, teichoic acid modification genes, and other genes involved in cell surface modification. Transmission electron microscopy showed that the cell walls of both strains J4206 and SA1 were significantly thicker and more electron dense than daptomycin- and vancomycin-sensitive strain J4211. This comparative genomic study has identified unique genes as well as allelic variants in the J4206 genome that are involved in cell surface modification and thus might contribute to the acquisition of daptomycin resistance.
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Affiliation(s)
- Maliha Rahman
- Department of Pharmaceutical Sciences, The University of Oklahoma College of PharmacyOklahoma, OK
| | - Scott V Nguyen
- Department of Pharmaceutical Sciences, The University of Oklahoma College of PharmacyOklahoma, OK.,Present address: U.S. Meat Animal Research Center, Clay Center, NE
| | - Kimberly A McCullor
- Department of Pharmaceutical Sciences, The University of Oklahoma College of PharmacyOklahoma, OK
| | - Catherine J King
- Department of Pharmaceutical Sciences, The University of Oklahoma College of PharmacyOklahoma, OK
| | - James H Jorgensen
- Department of Pathology, University of Texas Health Sciences Center at San Antonio, San Antonio, TX.,Department of Medicine, University of Texas Health Sciences Center at San Antonio, San Antonio, TX
| | - W Michael McShan
- Department of Pharmaceutical Sciences, The University of Oklahoma College of PharmacyOklahoma, OK
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Draft Genome Sequence of Streptococcus anginosus BVI, a New Vaginal Pathogen Candidate. GENOME ANNOUNCEMENTS 2016; 4:4/6/e01417-16. [PMID: 27979955 PMCID: PMC5159588 DOI: 10.1128/genomea.01417-16] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Streptococcus anginosus is a pathogen implicated in urogenital and gastroinstestinal tract infections. Here, we report the draft genome sequence of S. anginosus BVI, isolated from a bacterial vaginosis patient attending a prenatal care unit in Cali, Colombia. The genome sequence of BVI consists of 2,014,025 bp, encoding 2,008 predicted proteins.
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Application of Identification of Bacteria by DNA Target Sequencing in a Clinical Microbiology Laboratory. Mol Microbiol 2016. [DOI: 10.1128/9781555819071.ch2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Complete Genome Sequence of Streptococcus anginosus J4211, a Clinical Isolate. GENOME ANNOUNCEMENTS 2015; 3:3/6/e01440-15. [PMID: 26679576 PMCID: PMC4683221 DOI: 10.1128/genomea.01440-15] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Streptococcus anginosus is an opportunistic human pathogen that causes abscesses of the brain, liver, and other organs. Here, we announce the complete genome sequence of a clinically isolated strain of S. anginosus J4211. The genome sequence contains two prophages and multiple mobile genetic elements.
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Comparing Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry and Phenotypic and Molecular Methods for Identification of Species within the Streptococcus anginosus Group. J Clin Microbiol 2015; 53:3580-8. [PMID: 26354817 DOI: 10.1128/jcm.01892-15] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2015] [Accepted: 09/01/2015] [Indexed: 11/20/2022] Open
Abstract
The heterogeneity of members of the Streptococcus anginosus group (SAG) has traditionally hampered their correct identification. Recently, the group was subdivided into 6 taxa whose prevalence among human infections is poorly described. We evaluated the accuracy of the Rapid ID32 Strep test, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), and a PCR multiplex method to identify 212 SAG isolates recovered from human infections to the species and subspecies level by using multilocus sequence analysis (MLSA) as the gold standard. We also determined the antimicrobial susceptibilities of the isolates. Representatives of all SAG taxa were found among our collection. MALDI-TOF MS and the Rapid ID32 Strep test correctly identified 92% and 68% of the isolates to the species level, respectively, but showed poor performance at the subspecies level, and the latter was responsible for major identification errors. The multiplex PCR method results were in complete agreement with the MLSA identifications but failed to distinguish the subspecies Streptococcus constellatus subsp. pharyngis and S. constellatus subsp. viborgensis. A total of 145 MLSA sequence types were present in our collection, indicating that within each taxon a number of different lineages are capable of causing infection. Significant antibiotic resistance was observed only to tetracycline, erythromycin, and clindamycin and was present in most taxa. MALDI-TOF MS is a reliable method for routine SAG species identification, while the need for identification to the subspecies level is not clearly established.
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Taxonomic update on proposed nomenclature and classification changes for bacteria of medical importance, 2013-2014. Diagn Microbiol Infect Dis 2015; 83:82-8. [PMID: 26014276 DOI: 10.1016/j.diagmicrobio.2015.04.013] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2015] [Accepted: 04/28/2015] [Indexed: 12/21/2022]
Abstract
A key aspect of medical, public health, and diagnostic microbiology laboratories is the accurate and rapid reporting and communications regarding infectious agents of clinical significance. Microbial taxonomy in the age of molecular diagnostics and phylogenetics causes changes in this taxonomy at a rapid rate further complicating this process. This review focuses on the description of new species and classification changes proposed over the past 2 years.
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How an Opportunistic Infection Can Mess with Your Brain and Take Your Breath Away: A Rare Case of Simultaneous Lung and Brain Abscess due to Streptococcus anginosus. Case Rep Infect Dis 2015; 2015:462459. [PMID: 25922772 PMCID: PMC4397419 DOI: 10.1155/2015/462459] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2015] [Revised: 03/22/2015] [Accepted: 03/23/2015] [Indexed: 12/03/2022] Open
Abstract
Streptococcus anginosus (S. anginosus) is considered a friendly bug and is a one of many different bacteria that constitute the normal flora of the oral cavity. Nevertheless, it has been infrequently associated with more invasive infections, like lung abscess. It is extremely rare to have multisystemic involvement with S. anginosus group. We present a unique case of pulmonary and brain abscess due to S. anginosus in an immunocompetent patient.
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Asam D, Spellerberg B. Molecular pathogenicity of Streptococcus anginosus. Mol Oral Microbiol 2014; 29:145-55. [PMID: 24848553 DOI: 10.1111/omi.12056] [Citation(s) in RCA: 86] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/17/2014] [Indexed: 01/21/2023]
Abstract
Streptococcus anginosus and the closely related species Streptococcus constellatus and Streptococcus intermedius, are primarily commensals of the mucosa. The true pathogenic potential of this group has been under-recognized for a long time because of difficulties in correct species identification as well as the commensal nature of these species. In recent years, streptococci of the S. anginosus group have been increasingly found as relevant microbial pathogens in abscesses and blood cultures and they play a pathogenic role in cystic fibrosis. Several international studies have shown a surprisingly high frequency of infections caused by the S. anginosus group. Recent studies and a genome-wide comparative analysis suggested the presence of multiple putative virulence factors that are well-known from other streptococcal species. However, very little is known about the molecular basis of pathogenicity in these bacteria. This review summarizes our current knowledge of pathogenicity factors and their regulation in S. anginosus.
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Affiliation(s)
- D Asam
- Institute of Medical Microbiology and Hospital Hygiene, University of Ulm, Ulm, Germany
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Identification and characterization of a novel secreted glycosidase with multiple glycosidase activities in Streptococcus intermedius. J Bacteriol 2014; 196:2817-26. [PMID: 24858187 DOI: 10.1128/jb.01727-14] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Streptococcus intermedius is a known human pathogen and belongs to the anginosus group (S. anginosus, S. intermedius, and S. constellatus) of streptococci (AGS). We found a large open reading frame (6,708 bp) in the lac operon, and bioinformatic analysis suggested that this gene encodes a novel glycosidase that can exhibit β-d-galactosidase and N-acetyl-β-d-hexosaminidase activities. We, therefore, named this protein "multisubstrate glycosidase A" (MsgA). To test whether MsgA has these glycosidase activities, the msgA gene was disrupted in S. intermedius. The msgA-deficient mutant no longer showed cell- and supernatant-associated β-d-galactosidase, β-d-fucosidase, N-acetyl-β-d-glucosaminidase, and N-acetyl-β-d-galactosaminidase activities, and all phenotypes were complemented in trans with a recombinant plasmid carrying msgA. Purified MsgA had all four of these glycosidase activities and exhibited the lowest Km with 4-methylumbelliferyl-linked N-acetyl-β-d-glucosaminide and the highest kcat with 4-methylumbelliferyl-linked β-d-galactopyranoside. In addition, the purified LacZ domain of MsgA had β-d-galactosidase and β-d-fucosidase activities, and the GH20 domain exhibited both N-acetyl-β-d-glucosaminidase and N-acetyl-β-d-galactosaminidase activities. The β-d-galactosidase and β-d-fucosidase activities of MsgA are thermolabile, and the optimal temperature of the reaction was 40°C, whereas almost all enzymatic activities disappeared at 49°C. The optimal temperatures for the N-acetyl-β-d-glucosaminidase and N-acetyl-β-d-galactosaminidase activities were 58 and 55°C, respectively. The requirement of sialidase treatment to remove sialic acid residues of the glycan branch end for glycan degradation by MsgA on human α1-antitrypsin indicates that MsgA has exoglycosidase activities. MsgA and sialidase might have an important function in the production and utilization of monosaccharides from oligosaccharides, such as glycans for survival in a normal habitat and for pathogenicity of S. intermedius.
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Tabata A, Sato Y, Maya K, Nakano K, Kikuchi K, Whiley RA, Ohkura K, Tomoyasu T, Nagamune H. A streptolysin S homologue is essential for β-haemolytic Streptococcus constellatus subsp. constellatus cytotoxicity. MICROBIOLOGY-SGM 2014; 160:980-991. [PMID: 24600025 DOI: 10.1099/mic.0.075580-0] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Streptococcus constellatus is a member of the Anginosus group streptococci (AGS) and primarily inhabits the human oral cavity. S. constellatus is composed of three subspecies: S. constellatus subsp. constellatus (SCC), S. constellatus subsp. pharyngis and the newly described subspecies S. constellatus subsp. viborgensis. Although previous studies have established that SCC contains β-haemolytic strains, the factor(s) responsible for β-haemolysis in β-haemolytic SCC (β-SCC) has yet to be clarified. Recently, we discovered that a streptolysin S (SLS) homologue is the β-haemolytic factor of β-haemolytic Streptococcus anginosus subsp. anginosus (β-SAA), another member of the AGS. Furthermore, because previous studies have suggested that other AGS species, except for Streptococcus intermedius, do not possess a haemolysin(s) belonging to the family of cholesterol-dependent cytolysins, we hypothesized that, as with β-SAA, the SLS homologue is the β-haemolytic factor of β-SCC, and therefore aimed to investigate and characterize the haemolytic factor of β-SCC in the present study. PCR amplification revealed that all of the tested β-SCC strains were positive for the sagA homologue of SCC (sagA(SCC)). Further investigations using β-SCC strain W277 were conducted to elucidate the relationship between sagA(SCC) and β-haemolysis by constructing sagA(SCC) deletion mutants, which completely lost β-haemolytic activity. This loss of β-haemolytic activity was restored by trans-complementation of sagA(SCC). Furthermore, a co-cultivation assay established that the cytotoxicity of β-SCC was clearly dependent on the presence of sagA(SCC). These results demonstrate that sagA(SCC) is the factor responsible for β-SCC β-haemolysis and cytotoxicity.
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Affiliation(s)
- Atsushi Tabata
- Department of Biological Science and Technology, Life System, Institute of Technology and Science, The University of Tokushima Graduate School, 2-1 Minamijosanjima-cho, Tokushima, Tokushima 770-8506, Japan
| | - Yuji Sato
- Department of Biological Science and Technology, Life System, Institute of Technology and Science, The University of Tokushima Graduate School, 2-1 Minamijosanjima-cho, Tokushima, Tokushima 770-8506, Japan
| | - Kentaro Maya
- Department of Biological Science and Technology, Life System, Institute of Technology and Science, The University of Tokushima Graduate School, 2-1 Minamijosanjima-cho, Tokushima, Tokushima 770-8506, Japan
| | - Kota Nakano
- Department of Biological Science and Technology, Life System, Institute of Technology and Science, The University of Tokushima Graduate School, 2-1 Minamijosanjima-cho, Tokushima, Tokushima 770-8506, Japan
| | - Ken Kikuchi
- Department of Infection Control Science, Faculty of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
| | - Robert A Whiley
- Department of Clinical and Diagnostic Oral Sciences, Institute of Dentistry, Bart's and The London School of Medicine and Dentistry, Queen Mary University of London, Turner Street, London E1 2AD, UK
| | - Kazuto Ohkura
- Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3 Minamitamagaki-cho, Suzuka, Mie 513-0816, Japan
| | - Toshifumi Tomoyasu
- Department of Biological Science and Technology, Life System, Institute of Technology and Science, The University of Tokushima Graduate School, 2-1 Minamijosanjima-cho, Tokushima, Tokushima 770-8506, Japan
| | - Hideaki Nagamune
- Department of Biological Science and Technology, Life System, Institute of Technology and Science, The University of Tokushima Graduate School, 2-1 Minamijosanjima-cho, Tokushima, Tokushima 770-8506, Japan
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Olson AB, Kent H, Sibley CD, Grinwis ME, Mabon P, Ouellette C, Tyson S, Graham M, Tyler SD, Van Domselaar G, Surette MG, Corbett CR. Phylogenetic relationship and virulence inference of Streptococcus Anginosus Group: curated annotation and whole-genome comparative analysis support distinct species designation. BMC Genomics 2013; 14:895. [PMID: 24341328 PMCID: PMC3897883 DOI: 10.1186/1471-2164-14-895] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2013] [Accepted: 12/09/2013] [Indexed: 12/30/2022] Open
Abstract
Background The Streptococcus Anginosus Group (SAG) represents three closely related species of the viridans group streptococci recognized as commensal bacteria of the oral, gastrointestinal and urogenital tracts. The SAG also cause severe invasive infections, and are pathogens during cystic fibrosis (CF) pulmonary exacerbation. Little genomic information or description of virulence mechanisms is currently available for SAG. We conducted intra and inter species whole-genome comparative analyses with 59 publically available Streptococcus genomes and seven in-house closed high quality finished SAG genomes; S. constellatus (3), S. intermedius (2), and S. anginosus (2). For each SAG species, we sequenced at least one numerically dominant strain from CF airways recovered during acute exacerbation and an invasive, non-lung isolate. We also evaluated microevolution that occurred within two isolates that were cultured from one individual one year apart. Results The SAG genomes were most closely related to S. gordonii and S. sanguinis, based on shared orthologs and harbor a similar number of proteins within each COG category as other Streptococcus species. Numerous characterized streptococcus virulence factor homologs were identified within the SAG genomes including; adherence, invasion, spreading factors, LPxTG cell wall proteins, and two component histidine kinases known to be involved in virulence gene regulation. Mobile elements, primarily integrative conjugative elements and bacteriophage, account for greater than 10% of the SAG genomes. S. anginosus was the most variable species sequenced in this study, yielding both the smallest and the largest SAG genomes containing multiple genomic rearrangements, insertions and deletions. In contrast, within the S. constellatus and S. intermedius species, there was extensive continuous synteny, with only slight differences in genome size between strains. Within S. constellatus we were able to determine important SNPs and changes in VNTR numbers that occurred over the course of one year. Conclusions The comparative genomic analysis of the SAG clarifies the phylogenetics of these bacteria and supports the distinct species classification. Numerous potential virulence determinants were identified and provide a foundation for further studies into SAG pathogenesis. Furthermore, the data may be used to enable the development of rapid diagnostic assays and therapeutics for these pathogens.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | - Michael G Surette
- National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada.
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