{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T14:52:14Z","timestamp":1793112734858,"version":"4.5.0"},"update-to":[{"DOI":"10.1371\/journal.pgen.1011229","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T00:00:00Z","timestamp":1716249600000}}],"reference-count":126,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T00:00:00Z","timestamp":1714608000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000185","name":"Defense Advanced Research Projects Agency","doi-asserted-by":"publisher","award":["D17AP00004"],"award-info":[{"award-number":["D17AP00004"]}],"id":[{"id":"10.13039\/100000185","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000185","name":"Defense Advanced Research Projects Agency","doi-asserted-by":"publisher","award":["D17AP00004"],"award-info":[{"award-number":["D17AP00004"]}],"id":[{"id":"10.13039\/100000185","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p><jats:italic>Staphylococcus aureus<\/jats:italic> (<jats:italic>S<\/jats:italic>. <jats:italic>aureus<\/jats:italic>) is an opportunistic pathogen causing diseases ranging from mild skin infections to life threatening conditions, including endocarditis, pneumonia, and sepsis. To identify host genes modulating this host-pathogen interaction, we infected 25 Collaborative Cross (CC) mouse strains with methicillin-resistant <jats:italic>S<\/jats:italic>. <jats:italic>aureus<\/jats:italic> (MRSA) and monitored disease progression for seven days using a surgically implanted telemetry system. CC strains varied widely in their response to intravenous MRSA infection. We identified eight \u2018susceptible\u2019 CC strains with high bacterial load, tissue damage, and reduced survival. Among the surviving strains, six with minimal colonization were classified as \u2018resistant\u2019, while the remaining six tolerated higher organ colonization (\u2018tolerant\u2019). The kidney was the most heavily colonized organ, but liver, spleen and lung colonization were better correlated with reduced survival. Resistant strains had higher pre-infection circulating neutrophils and lower post-infection tissue damage compared to susceptible and tolerant strains. We identified four CC strains with sexual dimorphism: all females survived the study period while all males met our euthanasia criteria earlier. In these CC strains, males had more baseline circulating monocytes and red blood cells. We identified several CC strains that may be useful as new models for endocarditis, myocarditis, pneumonia, and resistance to MRSA infection. Quantitative Trait Locus (QTL) analysis identified two significant loci, on Chromosomes 18 and 3, involved in early susceptibility and late survival after infection. We prioritized <jats:italic>Npc1<\/jats:italic> and <jats:italic>Ifi44l<\/jats:italic> genes as the strongest candidates influencing survival using variant analysis and mRNA expression data from kidneys within these intervals.<\/jats:p>","DOI":"10.1371\/journal.pgen.1011229","type":"journal-article","created":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T17:47:03Z","timestamp":1714672023000},"page":"e1011229","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["Collaborative Cross mice have diverse phenotypic responses to infection with Methicillin-resistant Staphylococcus aureus USA300"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9613-3729","authenticated-orcid":true,"given":"Aravindh","family":"Nagarajan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6156-2224","authenticated-orcid":true,"given":"Kristin","family":"Scoggin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyotsana","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5970-9709","authenticated-orcid":true,"given":"Manuchehr","family":"Aminian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7246-1602","authenticated-orcid":true,"given":"L. Garry","family":"Adams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Kirby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3538-1635","authenticated-orcid":true,"given":"David","family":"Threadgill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1818-1335","authenticated-orcid":true,"given":"Helene","family":"Andrews-Polymenis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,5,2]]},"reference":[{"issue":"8","key":"pgen.1011229.ref001","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1056\/NEJM199808203390806","article-title":"Staphylococcus aureus infections","volume":"339","author":"FD Lowy","year":"1998","journal-title":"N Engl J Med"},{"issue":"11","key":"pgen.1011229.ref002","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/nrmicro.2017.104","article-title":"The commensal lifestyle of Staphylococcus aureus and its interactions with the nasal microbiota","volume":"15","author":"B Krismer","year":"2017","journal-title":"Nat Rev Microbiol"},{"issue":"12","key":"pgen.1011229.ref003","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/S1473-3099(05)70295-4","article-title":"The role of nasal carriage in Staphylococcus aureus infections","volume":"5","author":"HF Wertheim","year":"2005","journal-title":"The Lancet infectious diseases"},{"issue":"2","key":"pgen.1011229.ref004","doi-asserted-by":"crossref","DOI":"10.1128\/microbiolspec.GPP3-0029-2018","article-title":"Staphylococcus aureus Colonization of the Human Nose and Interaction with Other Microbiome Members","volume":"7","author":"C Laux","year":"2019","journal-title":"Microbiol Spectr"},{"issue":"3","key":"pgen.1011229.ref005","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1128\/CMR.00134-14","article-title":"Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management","volume":"28","author":"SY Tong","year":"2015","journal-title":"Clin Microbiol Rev"},{"issue":"1","key":"pgen.1011229.ref006","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1128\/JCM.02423-12","article-title":"Impact of strain typing methods on assessment of relationship between paired nares and wound isolates of methicillin-resistant Staphylococcus aureus","volume":"51","author":"JE Clarridge","year":"2013","journal-title":"J Clin Microbiol"},{"key":"pgen.1011229.ref007","article-title":"Staphylococcus aureus host interactions and adaptation","author":"BP Howden","year":"2023","journal-title":"Nature Reviews Microbiology"},{"issue":"3","key":"pgen.1011229.ref008","article-title":"Staphylococcus aureus in Animals","volume":"7","author":"AF Haag","year":"2019","journal-title":"Microbiol Spectr"},{"issue":"6\u20137","key":"pgen.1011229.ref009","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.ijmm.2013.02.007","article-title":"Community-associated MRSA: what makes them special?","volume":"303","author":"M. 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