دورية أكاديمية
A high-throughput cytotoxicity screening platform reveals agr -independent mutations in bacteraemia-associated Staphylococcus aureus that promote intracellular persistence.
العنوان: | A high-throughput cytotoxicity screening platform reveals agr -independent mutations in bacteraemia-associated Staphylococcus aureus that promote intracellular persistence. |
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المؤلفون: | Hachani A; Department of Microbiology and Immunology, Doherty Institute, University of Melbourne, Melbourne, Australia., Giulieri SG; Department of Microbiology and Immunology, Doherty Institute, University of Melbourne, Melbourne, Australia., Guérillot R; Department of Microbiology and Immunology, Doherty Institute, University of Melbourne, Melbourne, Australia., Walsh CJ; Department of Microbiology and Immunology, Doherty Institute, University of Melbourne, Melbourne, Australia., Herisse M; Department of Microbiology and Immunology, Doherty Institute, University of Melbourne, Melbourne, Australia., Soe YM; Department of Microbiology and Immunology, Doherty Institute, University of Melbourne, Melbourne, Australia., Baines SL; Department of Microbiology and Immunology, Doherty Institute, University of Melbourne, Melbourne, Australia., Thomas DR; Department of Microbiology and Immunology, Doherty Institute, University of Melbourne, Melbourne, Australia.; Infection and Immunity Program, Department of Microbiology and Biomedicine Discovery Institute, Monash University, Clayton, Australia., Cheung SD; Biological Optical Microscopy Platform, University of Melbourne, Melbourne, Australia., Hayes AS; Department of Microbiology and Immunology, Doherty Institute, University of Melbourne, Melbourne, Australia., Cho E; Biological Optical Microscopy Platform, University of Melbourne, Melbourne, Australia., Newton HJ; Department of Microbiology and Immunology, Doherty Institute, University of Melbourne, Melbourne, Australia.; Infection and Immunity Program, Department of Microbiology and Biomedicine Discovery Institute, Monash University, Clayton, Australia., Pidot S; Department of Microbiology and Immunology, Doherty Institute, University of Melbourne, Melbourne, Australia., Massey RC; School of Microbiology, University College Cork, Cork, Ireland.; School of Medicine, University College Cork, Cork, Ireland.; APC Microbiome Ireland, University College Cork, Cork, Ireland.; School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom., Howden BP; Department of Microbiology and Immunology, Doherty Institute, University of Melbourne, Melbourne, Australia.; Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology and Immunology, Doherty Institute, University of Melbourne, Melbourne, Australia., Stinear TP; Department of Microbiology and Immunology, Doherty Institute, University of Melbourne, Melbourne, Australia. |
المصدر: | ELife [Elife] 2023 Jun 08; Vol. 12. Date of Electronic Publication: 2023 Jun 08. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: eLife Sciences Publications, Ltd Country of Publication: England NLM ID: 101579614 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-084X (Electronic) Linking ISSN: 2050084X NLM ISO Abbreviation: Elife Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Cambridge, UK : eLife Sciences Publications, Ltd., 2012- |
مواضيع طبية MeSH: | Staphylococcal Infections*/microbiology , Bacteremia*/microbiology, Humans ; Staphylococcus aureus/metabolism ; Mutation ; Cell Line ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism |
مستخلص: | Staphylococcus aureus infections are associated with high mortality rates. Often considered an extracellular pathogen, S. aureus can persist and replicate within host cells, evading immune responses, and causing host cell death. Classical methods for assessing S. aureus cytotoxicity are limited by testing culture supernatants and endpoint measurements that do not capture the phenotypic diversity of intracellular bacteria. Using a well-established epithelial cell line model , we have developed a platform called InToxSa ( in tracellular tox icity of S. a ureus ) to quantify intracellular cytotoxic S. aureus phenotypes. Studying a panel of 387 S . aureus bacteraemia isolates, and combined with comparative, statistical, and functional genomics, our platform identified mutations in S. aureus clinical isolates that reduced bacterial cytotoxicity and promoted intracellular persistence. In addition to numerous convergent mutations in the Agr quorum sensing system, our approach detected mutations in other loci that also impacted cytotoxicity and intracellular persistence. We discovered that clinical mutations in ausA , encoding the aureusimine non-ribosomal peptide synthetase, reduced S. aureus cytotoxicity, and increased intracellular persistence. InToxSa is a versatile, high-throughput cell-based phenomics platform and we showcase its utility by identifying clinically relevant S. aureus pathoadaptive mutations that promote intracellular residency. Competing Interests: AH, SG, RG, CW, MH, YS, SB, DT, SC, AH, EC, HN, SP, RM, BH, TS No competing interests declared (© 2023, Hachani, Giulieri, Guérillot et al.) |
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معلومات مُعتمدة: | GNT2018880 National Health and Medical Research Council; GNT1105525 National Health and Medical Research Council; GNT1145631 National Health and Medical Research Council; GNT1196103 National Health and Medical Research Council |
فهرسة مساهمة: | Keywords: GWAS; Staphylococcus aureus; bacterial population genomics; cytotoxicity; evolutionary convergence analysis; genetics; genomics; infectious disease; intracellular; microbiology |
المشرفين على المادة: | 0 (Bacterial Proteins) |
تواريخ الأحداث: | Date Created: 20230608 Date Completed: 20230612 Latest Revision: 20231116 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC10259494 |
DOI: | 10.7554/eLife.84778 |
PMID: | 37289634 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2050-084X |
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DOI: | 10.7554/eLife.84778 |