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
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author Berube, Bryan
Deshpande, Aditi
Bhagwat, Amala
Parish, Tanya
author_facet Berube, Bryan
Deshpande, Aditi
Bhagwat, Amala
Parish, Tanya
author_sort Berube, Bryan
collection PubMed
description 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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spelling pubmed-103337952023-07-12 Inoculum-dependent bactericidal activity of a Mycobacterium tuberculosis MmpL3 inhibitor Berube, Bryan Deshpande, Aditi Bhagwat, Amala Parish, Tanya Microbiology (Reading) Antimicrobials and AMR 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. Microbiology Society 2023-06-19 /pmc/articles/PMC10333795/ /pubmed/37334886 http://dx.doi.org/10.1099/mic.0.001345 Text en © 2023 The Authors https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License.
spellingShingle Antimicrobials and AMR
Berube, Bryan
Deshpande, Aditi
Bhagwat, Amala
Parish, Tanya
Inoculum-dependent bactericidal activity of a Mycobacterium tuberculosis MmpL3 inhibitor
title Inoculum-dependent bactericidal activity of a Mycobacterium tuberculosis MmpL3 inhibitor
title_full Inoculum-dependent bactericidal activity of a Mycobacterium tuberculosis MmpL3 inhibitor
title_fullStr Inoculum-dependent bactericidal activity of a Mycobacterium tuberculosis MmpL3 inhibitor
title_full_unstemmed Inoculum-dependent bactericidal activity of a Mycobacterium tuberculosis MmpL3 inhibitor
title_short Inoculum-dependent bactericidal activity of a Mycobacterium tuberculosis MmpL3 inhibitor
title_sort inoculum-dependent bactericidal activity of a mycobacterium tuberculosis mmpl3 inhibitor
topic Antimicrobials and AMR
url 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
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AT bhagwatamala inoculumdependentbactericidalactivityofamycobacteriumtuberculosismmpl3inhibitor
AT parishtanya inoculumdependentbactericidalactivityofamycobacteriumtuberculosismmpl3inhibitor

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