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dc.contributor.authorSmith, Clare M
dc.contributor.authorBaker, Richard E
dc.contributor.authorProulx, Megan K
dc.contributor.authorMishra, Bibhuti B
dc.contributor.authorLong, Jarukit E
dc.contributor.authorPark, Sae Woong
dc.contributor.authorLee, Ha-Na
dc.contributor.authorKiritsy, Michael C
dc.contributor.authorBellerose, Michelle M
dc.contributor.authorOlive, Andrew J
dc.contributor.authorMurphy, Kenan C
dc.contributor.authorPapavinasasundaram, Kadamba
dc.contributor.authorBoehm, Frederick J
dc.contributor.authorReames, Charlotte J
dc.contributor.authorMeade, Rachel K
dc.contributor.authorHampton, Brea K
dc.contributor.authorLinnertz, Colton L
dc.contributor.authorShaw, Ginger D
dc.contributor.authorHock, Pablo
dc.contributor.authorBell, Timothy A
dc.contributor.authorEhrt, Sabine
dc.contributor.authorSchnappinger, Dirk
dc.contributor.authorPardo-Manuel de Villena, Fernando
dc.contributor.authorFerris, Martin T
dc.contributor.authorIoerger, Thomas R
dc.contributor.authorSassetti, Christopher M
dc.date.accessioned2023-07-11T17:51:50Z
dc.date.available2023-07-11T17:51:50Z
dc.date.issued2022-02-03
dc.identifier.citationSmith CM, Baker RE, Proulx MK, Mishra BB, Long JE, Park SW, Lee HN, Kiritsy MC, Bellerose MM, Olive AJ, Murphy KC, Papavinasasundaram K, Boehm FJ, Reames CJ, Meade RK, Hampton BK, Linnertz CL, Shaw GD, Hock P, Bell TA, Ehrt S, Schnappinger D, Pardo-Manuel de Villena F, Ferris MT, Ioerger TR, Sassetti CM. Host-pathogen genetic interactions underlie tuberculosis susceptibility in genetically diverse mice. Elife. 2022 Feb 3;11:e74419. doi: 10.7554/eLife.74419. PMID: 35112666; PMCID: PMC8846590.en_US
dc.identifier.eissn2050-084X
dc.identifier.doi10.7554/eLife.74419en_US
dc.identifier.pmid35112666
dc.identifier.urihttp://hdl.handle.net/20.500.14038/52270
dc.description.abstractThe outcome of an encounter with Mycobacterium tuberculosis (Mtb) depends on the pathogen's ability to adapt to the variable immune pressures exerted by the host. Understanding this interplay has proven difficult, largely because experimentally tractable animal models do not recapitulate the heterogeneity of tuberculosis disease. We leveraged the genetically diverse Collaborative Cross (CC) mouse panel in conjunction with a library of Mtb mutants to create a resource for associating bacterial genetic requirements with host genetics and immunity. We report that CC strains vary dramatically in their susceptibility to infection and produce qualitatively distinct immune states. Global analysis of Mtb transposon mutant fitness (TnSeq) across the CC panel revealed that many virulence pathways are only required in specific host microenvironments, identifying a large fraction of the pathogen's genome that has been maintained to ensure fitness in a diverse population. Both immunological and bacterial traits can be associated with genetic variants distributed across the mouse genome, making the CC a unique population for identifying specific host-pathogen genetic interactions that influence pathogenesis.en_US
dc.language.isoenen_US
dc.relationThis article is based on a previously available preprint in bioRxiv, https://doi.org/10.1101/2020.12.01.405514en_US
dc.relation.ispartofeLifeen_US
dc.relation.urlhttps://doi.org/10.7554/elife.74419en_US
dc.rightsCopyright Smith et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.; Attribution 4.0 Internationalen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectTnSeqen_US
dc.subjectcollaborative crossen_US
dc.subjectgeneticsen_US
dc.subjectgenomicsen_US
dc.subjecthost-pathogen interactionsen_US
dc.subjectinfectious diseaseen_US
dc.subjectmicrobiologyen_US
dc.subjectmouseen_US
dc.subjectmouse modelsen_US
dc.subjectsystems geneticsen_US
dc.subjecttuberculosisen_US
dc.titleHost-pathogen genetic interactions underlie tuberculosis susceptibility in genetically diverse miceen_US
dc.typeJournal Articleen_US
dc.source.journaltitleeLife
dc.source.volume11
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryEngland
dc.identifier.journaleLife
refterms.dateFOA2023-07-11T17:51:54Z
dc.contributor.departmentMicrobiology and Physiological Systemsen_US


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Copyright Smith et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.; Attribution 4.0 International
Except where otherwise noted, this item's license is described as Copyright Smith et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.; Attribution 4.0 International