Distinct Bacterial Pathways Influence the Efficacy of Antibiotics against Mycobacterium tuberculosis
Abstract
Understanding how Mycobacterium tuberculosis survives during antibiotic treatment is necessary to rationally devise more effective tuberculosis (TB) chemotherapy regimens. Using genome-wide mutant fitness profiling and the mouse model of TB, we identified genes that alter antibiotic efficacy specifically in the infection environment and associated several of these genes with natural genetic variants found in drug-resistant clinical isolates. These data suggest strategies for synergistic therapies that accelerate bacterial clearance, and they identify mechanisms of adaptation to drug exposure that could influence treatment outcome.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 25, 2020
- Source ID
- 10.1128/msystems.00396-20
Entities
People
- Christopher M Sassetti
- Clare Smith
- Megan K. Proulx
- Michelle M Bellerose
- Richard E. Baker
- Thomas R. Ioerger
Organizations
- Department of Computer Science, University of Oxford
- National Institutes of Health
- United States Department of Defense
- University of Massachusetts Medical School