Department of Microbiology and Physiological Systems
Bacteria | Bacteriology | Genetics and Genomics | Immunology of Infectious Disease | Immunopathology | Pathogenic Microbiology
The 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.
Mycobacterium tuberculosis, genetics, host-pathogen interactions
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DOI of Published Version
bioRxiv 2020.12.01.405514; doi: https://doi.org/10.1101/2020.12.01.405514. Link to preprint on bioRxiv.
Smith CM, Baker RE, Proulx MK, Mishra BB, Long JE, Kiritsy MC, Bellerose M, Olive AJ, Murphy KC, Papavinasasundaram K, Boehm F, Reames C, Sassetti CM. (2020). Host-pathogen genetic interactions underlie tuberculosis susceptibility in genetically diverse mice [preprint]. UMass Chan Medical School Faculty Publications. https://doi.org/10.1101/2020.12.01.405514. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/1838
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