UMass Chan Medical School Faculty Publications
UMMS Affiliation
Department of Microbiology and Physiological Systems
Publication Date
2020-12-01
Document Type
Article Preprint
Disciplines
Bacteria | Bacteriology | Genetics and Genomics | Immunology of Infectious Disease | Immunopathology | Pathogenic Microbiology
Abstract
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.
Keywords
Mycobacterium tuberculosis, genetics, host-pathogen interactions
Rights and Permissions
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
DOI of Published Version
10.1101/2020.12.01.405514
Source
bioRxiv 2020.12.01.405514; doi: https://doi.org/10.1101/2020.12.01.405514. Link to preprint on bioRxiv.
Journal/Book/Conference Title
bioRxiv
Repository Citation
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
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Included in
Bacteria Commons, Bacteriology Commons, Genetics and Genomics Commons, Immunology of Infectious Disease Commons, Immunopathology Commons, Pathogenic Microbiology Commons
Comments
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. This article is a preprint.