Inoculum-dependent bactericidal activity of a Mycobacterium tuberculosis MmpL3 inhibitor
Abstract
Indolcarboxamides are a promising series of anti-tubercular agents, which target Mycobacterium tuberculosis MmpL3, the exporter of trehalose monomycolate, a key cell-wall component. We determined the kill kinetics of the lead indolcarboxamide NITD-349 and determined that while kill was rapid against low-density cultures, bactericidal activity was inoculum-dependent. A combination of NITD-349 with isoniazid (which inhibits mycolate synthesis) had an increased kill rate; this combination prevented the appearance of resistant mutants, even at higher inocula.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jun 19, 2023
- Source ID
- 10.1099/mic.0.001345
Entities
People
- Aditi Deshpande
- Amala Bhagwat
- Bryan Berube
- Tanya Parish
Organizations
- Gates Foundation
- National Institutes of Health
- University of Washington