bioRxivJClub
Cholesterol-activated VapC12 toxin modulates growth and drug susceptibility in Mycobacterium tuberculosis
bioRxiv · · Preprint · Open access
Hashmi, Singh + 11 more
Abstract ↗AI summary
The abstract is read at the publisher; the summary is JClub's.
Cholesterol activates the VapC12 toxin in Mycobacterium tuberculosis by competitively displacing VapB12 from the CRAC motif, restricting bacterial growth.
- Why it matters: Antimicrobial resistance and persistence hinder tuberculosis eradication, and the molecular basis for VapC12-linked growth and drug susceptibility is needed.
- What they did: The study identified a CRAC motif in VapC12, used heterologous expression in Mycobacterium smegmatis, determined the crystal structure of VapB12 at 1.6 Angstorm resolution, and applied structure-function analyses plus molecular modeling.
- The result: Pharmacologically inhibiting VapC12 alleviated cholesterol-mediated growth restriction and enhanced antibiotic activity, linking cholesterol sensing to toxin-antitoxin regulation and antibiotic susceptibility in M. tuberculosis.
The findingWhy it mattersWhat they didThe result
- Open access