InhA inhibitors have activity against non-replicating Mycobacterium tuberculosis

We previously identified a diazaborine series with potential for development as a new tuberculosis drug. This series has activity in vitro and in vivo and targets cell wall biosynthesis via inhibition of InhA. The overall aim of this study was to determine whether InhA inhibitors have activity again...

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Detalles Bibliográficos
Autores principales: Flint, Lindsay, Korkegian, Aaron, Parish, Tanya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671525/
https://www.ncbi.nlm.nih.gov/pubmed/33201882
http://dx.doi.org/10.1371/journal.pone.0239354
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author Flint, Lindsay
Korkegian, Aaron
Parish, Tanya
author_facet Flint, Lindsay
Korkegian, Aaron
Parish, Tanya
author_sort Flint, Lindsay
collection PubMed
description We previously identified a diazaborine series with potential for development as a new tuberculosis drug. This series has activity in vitro and in vivo and targets cell wall biosynthesis via inhibition of InhA. The overall aim of this study was to determine whether InhA inhibitors have activity against non-replicating Mycobacterium tuberculosis. We tested the ability of two molecules of the diazaborine series to kill non-replicating M. tuberculosis in the nutrient starvation model; both molecules were bactericidal, reducing viability by >3 logs in 21 days. Activity showed similar kill rates to other InhA inhibitors (isoniazid and NITD-916). We conclude that inhibition of InhA is bactericidal against nutrient-starved non-replicating M. tuberculosis.
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spelling pubmed-76715252020-11-19 InhA inhibitors have activity against non-replicating Mycobacterium tuberculosis Flint, Lindsay Korkegian, Aaron Parish, Tanya PLoS One Research Article We previously identified a diazaborine series with potential for development as a new tuberculosis drug. This series has activity in vitro and in vivo and targets cell wall biosynthesis via inhibition of InhA. The overall aim of this study was to determine whether InhA inhibitors have activity against non-replicating Mycobacterium tuberculosis. We tested the ability of two molecules of the diazaborine series to kill non-replicating M. tuberculosis in the nutrient starvation model; both molecules were bactericidal, reducing viability by >3 logs in 21 days. Activity showed similar kill rates to other InhA inhibitors (isoniazid and NITD-916). We conclude that inhibition of InhA is bactericidal against nutrient-starved non-replicating M. tuberculosis. Public Library of Science 2020-11-17 /pmc/articles/PMC7671525/ /pubmed/33201882 http://dx.doi.org/10.1371/journal.pone.0239354 Text en © 2020 Flint et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Flint, Lindsay
Korkegian, Aaron
Parish, Tanya
InhA inhibitors have activity against non-replicating Mycobacterium tuberculosis
title InhA inhibitors have activity against non-replicating Mycobacterium tuberculosis
title_full InhA inhibitors have activity against non-replicating Mycobacterium tuberculosis
title_fullStr InhA inhibitors have activity against non-replicating Mycobacterium tuberculosis
title_full_unstemmed InhA inhibitors have activity against non-replicating Mycobacterium tuberculosis
title_short InhA inhibitors have activity against non-replicating Mycobacterium tuberculosis
title_sort inha inhibitors have activity against non-replicating mycobacterium tuberculosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671525/
https://www.ncbi.nlm.nih.gov/pubmed/33201882
http://dx.doi.org/10.1371/journal.pone.0239354
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