Activity of Tricyclic Pyrrolopyrimidine Gyrase B Inhibitor against Mycobacterium abscessus

Tricyclic pyrrolopyrimidines (TPPs) are a new class of antibacterials inhibiting the ATPase of DNA gyrase. TPP8, a representative of this class, is active against Mycobacterium abscessus in vitro. Spontaneous TPP8 resistance mutations mapped to the ATPase domain of M. abscessus DNA gyrase, and the c...

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Autores principales: Madani, Abdeldjalil, Negatu, Dereje A., El Marrouni, Abdellatif, Miller, Randy R., Boyce, Christopher W., Murgolo, Nicholas, Bungard, Christopher J., Zimmerman, Matthew D., Dartois, Véronique, Gengenbacher, Martin, Olsen, David B., Dick, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2022
Materias:
Experimental Therapeutics
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9487482/
https://www.ncbi.nlm.nih.gov/pubmed/36005813
http://dx.doi.org/10.1128/aac.00669-22
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author Madani, Abdeldjalil
Negatu, Dereje A.
El Marrouni, Abdellatif
Miller, Randy R.
Boyce, Christopher W.
Murgolo, Nicholas
Bungard, Christopher J.
Zimmerman, Matthew D.
Dartois, Véronique
Gengenbacher, Martin
Olsen, David B.
Dick, Thomas
author_facet Madani, Abdeldjalil
Negatu, Dereje A.
El Marrouni, Abdellatif
Miller, Randy R.
Boyce, Christopher W.
Murgolo, Nicholas
Bungard, Christopher J.
Zimmerman, Matthew D.
Dartois, Véronique
Gengenbacher, Martin
Olsen, David B.
Dick, Thomas
author_sort Madani, Abdeldjalil
collection PubMed
description Tricyclic pyrrolopyrimidines (TPPs) are a new class of antibacterials inhibiting the ATPase of DNA gyrase. TPP8, a representative of this class, is active against Mycobacterium abscessus in vitro. Spontaneous TPP8 resistance mutations mapped to the ATPase domain of M. abscessus DNA gyrase, and the compound inhibited DNA supercoiling activity of recombinant M. abscessus enzyme. Further profiling of TPP8 in macrophage and mouse infection studies demonstrated proof-of-concept activity against M. abscessus ex vivo and in vivo.
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spelling pubmed-94874822022-09-21 Activity of Tricyclic Pyrrolopyrimidine Gyrase B Inhibitor against Mycobacterium abscessus Madani, Abdeldjalil Negatu, Dereje A. El Marrouni, Abdellatif Miller, Randy R. Boyce, Christopher W. Murgolo, Nicholas Bungard, Christopher J. Zimmerman, Matthew D. Dartois, Véronique Gengenbacher, Martin Olsen, David B. Dick, Thomas Antimicrob Agents Chemother Experimental Therapeutics Tricyclic pyrrolopyrimidines (TPPs) are a new class of antibacterials inhibiting the ATPase of DNA gyrase. TPP8, a representative of this class, is active against Mycobacterium abscessus in vitro. Spontaneous TPP8 resistance mutations mapped to the ATPase domain of M. abscessus DNA gyrase, and the compound inhibited DNA supercoiling activity of recombinant M. abscessus enzyme. Further profiling of TPP8 in macrophage and mouse infection studies demonstrated proof-of-concept activity against M. abscessus ex vivo and in vivo. American Society for Microbiology 2022-08-25 /pmc/articles/PMC9487482/ /pubmed/36005813 http://dx.doi.org/10.1128/aac.00669-22 Text en Copyright © 2022 Madani et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Experimental Therapeutics
Madani, Abdeldjalil
Negatu, Dereje A.
El Marrouni, Abdellatif
Miller, Randy R.
Boyce, Christopher W.
Murgolo, Nicholas
Bungard, Christopher J.
Zimmerman, Matthew D.
Dartois, Véronique
Gengenbacher, Martin
Olsen, David B.
Dick, Thomas
Activity of Tricyclic Pyrrolopyrimidine Gyrase B Inhibitor against Mycobacterium abscessus
title Activity of Tricyclic Pyrrolopyrimidine Gyrase B Inhibitor against Mycobacterium abscessus
title_full Activity of Tricyclic Pyrrolopyrimidine Gyrase B Inhibitor against Mycobacterium abscessus
title_fullStr Activity of Tricyclic Pyrrolopyrimidine Gyrase B Inhibitor against Mycobacterium abscessus
title_full_unstemmed Activity of Tricyclic Pyrrolopyrimidine Gyrase B Inhibitor against Mycobacterium abscessus
title_short Activity of Tricyclic Pyrrolopyrimidine Gyrase B Inhibitor against Mycobacterium abscessus
title_sort activity of tricyclic pyrrolopyrimidine gyrase b inhibitor against mycobacterium abscessus
topic Experimental Therapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9487482/
https://www.ncbi.nlm.nih.gov/pubmed/36005813
http://dx.doi.org/10.1128/aac.00669-22
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