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Volume 169, Issue 6

Inoculum-dependent bactericidal activity of a MmpL3 inhibitor Open Access

Abstract

Indolcarboxamides are a promising series of anti-tubercular agents, which target 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.

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Keyword(s): anti-tubercular , bactericidal activity , cell-wall inhibitor and tuberculosis drug discovery
Funding
This study was supported by the:
  • Bill and Melinda Gates Foundation (Award INV-005585)
    • Principle Award Recipient: TanyaParish
  • Bill and Melinda Gates Foundation (Award OPP1024038)
    • Principle Award Recipient: TanyaParish
  • National Institutes of Health (Award R01AI129360)
    • Principle Award Recipient: TanyaParish
© 2023 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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/content/journal/micro/10.1099/mic.0.001345
2023-06-19
2024-05-04
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Inoculum-dependent bactericidal activity of a Mycobacterium tuberculosis MmpL3 inhibitor
Microbiology 169, 001345 (2023); https://doi.org/10.1099/mic.0.001345
/content/journal/micro/10.1099/mic.0.001345
/content/journal/micro/10.1099/mic.0.001345
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