Host-pathogen genetic interactions underlie tuberculosis susceptibility in genetically diverse mice
Clare M Smith1,2, Richard E Baker1, Megan K Proulx1
1Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, United States.
Elife
|February 3, 2022
Summary
Understanding Mycobacterium tuberculosis (Mtb) infection requires studying host-pathogen genetics. This research used diverse mice and Mtb mutants to reveal how bacterial genes adapt to varied host immunity, uncovering new insights into tuberculosis pathogenesis.
Area of Science:
- Immunology
- Microbiology
- Genetics
Background:
- Host-pathogen interactions in tuberculosis (TB) are complex and difficult to model.
- Existing animal models do not fully capture TB disease heterogeneity.
Purpose of the Study:
- To associate bacterial genetic requirements with host genetics and immunity during Mycobacterium tuberculosis (Mtb) infection.
- To create a resource for studying host-pathogen genetic interactions in TB.
Main Methods:
- Utilized the genetically diverse Collaborative Cross (CC) mouse panel.
- Employed a library of Mtb transposon mutants (TnSeq) for fitness analysis.
- Analyzed bacterial fitness across different CC mouse strains and their immune states.
Main Results:
- CC mouse strains exhibited significant variation in susceptibility and immune responses to Mtb.
- Many Mtb virulence pathways were found to be essential only in specific host microenvironments.
- Identified bacterial genes maintained for fitness across a diverse host population.
Conclusions:
- The CC mouse panel is a valuable resource for dissecting host-pathogen genetic interactions in TB.
- Bacterial adaptation strategies are shaped by diverse host immune pressures.
- Host genetic variation significantly influences Mtb pathogenesis and bacterial survival.
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