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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Detalles Bibliográficos
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
Descripción
Sumario: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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