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dc.contributor.authorGiulieri, Stefano G-
dc.contributor.authorGuérillot, Romain-
dc.contributor.authorDuchene, Sebastian-
dc.contributor.authorHachani, Abderrahman-
dc.contributor.authorDaniel, Diane-
dc.contributor.authorSeemann, Torsten-
dc.contributor.authorDavis, Joshua S-
dc.contributor.authorTong, Steven Y C-
dc.contributor.authorYoung, Bernadette C-
dc.contributor.authorWilson, Daniel J-
dc.contributor.authorStinear, Timothy P-
dc.contributor.authorHowden, Benjamin P-
dc.identifier.citationeLife 2022; 11: e77195en
dc.description.abstractDuring severe infections, Staphylococcus aureus moves from its colonising sites to blood and tissues and is exposed to new selective pressures, thus, potentially driving adaptive evolution. Previous studies have shown the key role of the agr locus in S. aureus pathoadaptation; however, a more comprehensive characterisation of genetic signatures of bacterial adaptation may enable prediction of clinical outcomes and reveal new targets for treatment and prevention of these infections. Here, we measured adaptation using within-host evolution analysis of 2590 S. aureus genomes from 396 independent episodes of infection. By capturing a comprehensive repertoire of single nucleotide and structural genome variations, we found evidence of a distinctive evolutionary pattern within the infecting populations compared to colonising bacteria. These invasive strains had up to 20-fold enrichments for genome degradation signatures and displayed significantly convergent mutations in a distinctive set of genes, linked to antibiotic response and pathogenesis. In addition to agr-mediated adaptation, we identified non-canonical, genome-wide significant loci including sucA-sucB and stp1. The prevalence of adaptive changes increased with infection extent, emphasising the clinical significance of these signatures. These findings provide a high-resolution picture of the molecular changes when S. aureus transitions from colonisation to severe infection and may inform correlation of infection outcomes with adaptation signatures.en
dc.subjectStaphylococcus aureusen
dc.subjectinfectious diseaseen
dc.subjectwithin-host evolutionen
dc.titleNiche-specific genome degradation and convergent evolution shaping Staphylococcus aureus adaptation during severe infections.en
dc.typeJournal Articleen
dc.identifier.affiliationInfectious Diseasesen
dc.identifier.affiliationDepartment of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia..en
dc.identifier.affiliationVictorian Infectious Diseases Service, Royal Melbourne Hospital, Melbourne, Australia..en
dc.identifier.affiliationMicrobiological Diagnostic Unit Public Health Laboratory, The University of Melbourne at the Doherty Institute for Infection and Immunity, Melbourne, Australia..en
dc.identifier.affiliationMenzies School of Health Research, Charles Darwin University, Casuarina, Northern Territory, Australia..en
dc.identifier.affiliationDepartment of Infectious Diseases, John Hunter Hospital, Newcastle, New South Wales, Australia..en
dc.identifier.affiliationVictorian Infectious Disease Service, Royal Melbourne Hospital, and University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia..en
dc.identifier.affiliationNuffield Department of medicine, Oxford, United Kingdom..en
dc.identifier.affiliationBig Data Institute, Nuffield Department of Population Health, Li Ka Shing Centre for Health Information and Discovery, Old Road Campus, University of Oxford, Oxford, United Kingdom..en
dc.identifier.pubmedid35699423, Stefano G
item.fulltextNo Fulltext-
item.openairetypeJournal Article-
item.languageiso639-1en- Diseases- Diseases-
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