Inoculum-dependent bactericidal activity of a Mycobacterium tuberculosis MmpL3 inhibitor

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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...

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Detalles Bibliográficos
Autores principales: Berube, Bryan, Deshpande, Aditi, Bhagwat, Amala, Parish, Tanya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Microbiology Society 2023
Materias:
Antimicrobials and AMR
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10333795/
https://www.ncbi.nlm.nih.gov/pubmed/37334886
http://dx.doi.org/10.1099/mic.0.001345
Descripción
Sumario: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.

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