Host-pathogen genetic interactions underlie tuberculosis susceptibility in genetically diverse mice [preprint]
AuthorsSmith, Clare M.
Baker, Richard E.
Proulx, Megan K.
Mishra, Bibhuti B.
Long, Jarukit E.
Kiritsy, Michael C.
Olive, Andrew J.
Murphy, Kenan C
Sassetti, Christopher M.
UMass Chan AffiliationsDepartment of Microbiology and Physiological Systems
Genetics and Genomics
Immunology of Infectious Disease
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AbstractThe outcome of an encounter with Mycobacterium tuberculosis (Mtb) depends on the pathogen’s ability to adapt to the heterogeneous immune response of the host. Understanding this interplay has proven difficult, largely because experimentally tractable small animal models do not recapitulate the heterogenous disease observed in natural infections. We leveraged the genetically diverse Collaborative Cross (CC) mouse panel in conjunction with a library of Mtb mutants to associate bacterial genetic requirements with host genetics and immunity. We report that CC strains vary dramatically in their susceptibility to infection and represent reproducible models of qualitatively distinct immune states. Global analysis of Mtb mutant fitness across the CC panel revealed that a large fraction of the pathogen’s genome is necessary for adaptation to specific host microenvironments. Both immunological and bacterial traits were associated with genetic variants distributed across the mouse genome, elucidating the complex genetic landscape that underlies host-pathogen interactions in a diverse population.
bioRxiv 2020.12.01.405514; doi: https://doi.org/10.1101/2020.12.01.405514. Link to preprint on bioRxiv.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/29620
This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.
Full author list omitted for brevity. For the full list of authors, see article.