Common Variants in the Glycerol Kinase Gene Reduce Tuberculosis Drug Efficacy
Abstract
TB control is limited in part by the length of antibiotic treatment needed to prevent recurrent disease. To probe mechanisms underlying survival under antibiotic pressure, we performed a genetic screen for M. tuberculosis mutants with altered susceptibility to treatment using the mouse model of TB. We identified multiple genes involved in a range of functions which alter sensitivity to antibiotics. In particular, we found glycerol catabolism mutants were less susceptible to treatment and that common variation in a homopolymeric region in the glpK gene was associated with drug resistance in clinical isolates. These studies indicate that reversible high-frequency variation in carbon metabolic pathways can produce phenotypically drug-tolerant clones and have a role in the development of resistance.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 27, 2019
- Source ID
- 10.1128/mbio.00663-19
Entities
People
- Caitlin E. Moss
- Christopher M Sassetti
- Chuan-chin Huang
- Clare Smith
- Eun-ik Koh
- Jong Seok Lee
- Megan K. Proulx
- Megan Murray
- Michelle M Bellerose
- Richard E. Baker
- Sang-nae Cho
- Seokyong Eum
- Seung-hun Baek
- Sung Jae Shin
Organizations
- Congressionally Directed Medical Research Programs
- Harvard Medical School
- International Tuberculosis Research Center
- National Institutes of Health
- University of Massachusetts Medical School
- Yonsei University