{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:26:06Z","timestamp":1790519166065,"version":"4.1.0"},"reference-count":85,"publisher":"Microbiology Society","issue":"11","license":[{"start":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T00:00:00Z","timestamp":1638230400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013373","name":"nihr oxford biomedical research centre","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100013373","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100008551","name":"fondation m\u00e9rieux","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008551","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000272","name":"national institute for health research","doi-asserted-by":"crossref","award":["HPRU-2012-10041"],"award-info":[{"award-number":["HPRU-2012-10041"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010269","name":"wellcome trust","doi-asserted-by":"crossref","award":["WT098615\/Z\/12\/Z"],"award-info":[{"award-number":["WT098615\/Z\/12\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"name":"department of health","award":["grant HICF-T5-358"],"award-info":[{"award-number":["grant HICF-T5-358"]}]},{"DOI":"10.13039\/100010269","name":"wellcome trust","doi-asserted-by":"crossref","award":["203141\/Z\/16\/Z"],"award-info":[{"award-number":["203141\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010269","name":"wellcome trust","doi-asserted-by":"crossref","award":["Grant 101237\/Z\/13\/B"],"award-info":[{"award-number":["Grant 101237\/Z\/13\/B"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010269","name":"wellcome trust","doi-asserted-by":"crossref","award":["Grant 101611\/Z\/13\/Z"],"award-info":[{"award-number":["Grant 101611\/Z\/13\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,30]]},"abstract":"\n \n \n Staphylococcus aureus<\/jats:ext-link>\n <\/jats:named-content>\n <\/jats:italic>\n is a major bacterial pathogen in humans, and a dominant cause of severe bloodstream infections. Globally, antimicrobial resistance (AMR) in\n \n \n S. aureus<\/jats:ext-link>\n <\/jats:named-content>\n <\/jats:italic>\n remains challenging. While human risk factors for infection have been defined, contradictory evidence exists for the role of bacterial genomic variation in\n \n \n S. aureus<\/jats:ext-link>\n <\/jats:named-content>\n <\/jats:italic>\n disease. To investigate the contribution of bacterial lineage and genomic variation to the development of bloodstream infection, we undertook a genome-wide association study comparing bacteria from 1017 individuals with bacteraemia to 984 adults with asymptomatic\n \n \n S. aureus<\/jats:ext-link>\n <\/jats:named-content>\n <\/jats:italic>\n nasal carriage. Within 984 carriage isolates, we also compared healthcare-associated (HA) carriage with community-associated (CA) carriage. All major global lineages were represented in both bacteraemia and carriage, with no evidence for different infection rates. However, kmers tagging trimethoprim resistance-conferring mutation F99Y in\n dfrB<\/jats:italic>\n were significantly associated with bacteraemia-vs-carriage (\n P=<\/jats:italic>\n 10\n -8.9<\/jats:sup>\n -10\n -9.3<\/jats:sup>\n ). Pooling variation within genes, bacteraemia-vs-carriage was associated with the presence of\n mecA<\/jats:italic>\n (HMP=10\n -5.3<\/jats:sup>\n ) as well as the presence of SCCmec (HMP=10\n -4.4<\/jats:sup>\n ). Among\n \n \n S. aureus<\/jats:ext-link>\n <\/jats:named-content>\n <\/jats:italic>\n carriers, no lineages were associated with HA-vs-CA carriage. However, we found a novel signal of HA-vs-CA carriage in the foldase protein\n prsA<\/jats:italic>\n , where kmers representing conserved sequence allele were associated with CA carriage (\n P=<\/jats:italic>\n 10\n -7.1<\/jats:sup>\n -10\n -19.4<\/jats:sup>\n ), while in\n gyrA<\/jats:italic>\n , a ciprofloxacin resistance-conferring mutation, L84S, was associated with HA carriage (\n P=<\/jats:italic>\n 10\n -7.2<\/jats:sup>\n ). In an extensive study of\n \n \n S. aureus<\/jats:ext-link>\n <\/jats:named-content>\n <\/jats:italic>\n bacteraemia and nasal carriage in the UK, we found strong evidence that all\n \n \n S. aureus<\/jats:ext-link>\n <\/jats:named-content>\n <\/jats:italic>\n lineages are equally capable of causing bloodstream infection, and of being carried in the healthcare environment. Genomic variation in the foldase protein\n prsA<\/jats:italic>\n is a novel genomic marker of healthcare origin in\n \n \n S. aureus<\/jats:ext-link>\n <\/jats:named-content>\n <\/jats:italic>\n but was not associated with bacteraemia. AMR determinants were associated with both bacteraemia and healthcare-associated carriage, suggesting that AMR increases the propensity not only to survive in healthcare environments, but also to cause invasive disease.\n <\/jats:p>","DOI":"10.1099\/mgen.0.000700","type":"journal-article","created":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T10:15:41Z","timestamp":1637662541000},"source":"Crossref","is-referenced-by-count":24,"title":["Antimicrobial resistance determinants are associated with Staphylococcus aureus bacteraemia and adaptation to the healthcare environment: a bacterial genome-wide association study"],"prefix":"10.1099","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6071-6770","authenticated-orcid":false,"given":"Bernadette C.","family":"Young","sequence":"first","affiliation":[{"name":"Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK"},{"name":"Microbiology and Infectious Diseases Department, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9386-725X","authenticated-orcid":false,"given":"Chieh-Hsi","family":"Wu","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9759-9838","authenticated-orcid":false,"given":"Jane","family":"Charlesworth","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0738-7557","authenticated-orcid":false,"given":"Sarah","family":"Earle","sequence":"additional","affiliation":[{"name":"Big Data Institute, Nuffield Department of Population Health, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Old Road Campus, Oxford, OX3 7LF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2541-8545","authenticated-orcid":false,"given":"James R.","family":"Price","sequence":"additional","affiliation":[{"name":"Department of Global Health and Infection, Brighton and Sussex Medical School, University of Sussex, Falmer BN1 9PS, UK"},{"name":"Department of Infectious Diseases and Microbiology, Royal Sussex County Hospital, Brighton BN2 5BE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8266-3630","authenticated-orcid":false,"given":"N. 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