Benzene Amide Ether Scaffold is Active against Non-replicating and Intracellular Mycobacterium tuberculosis.
ACS Infect Dis
; 9(10): 1981-1992, 2023 10 13.
Article
en En
| MEDLINE
| ID: mdl-37708378
ABSTRACT
New drugs to treat tuberculosis which target intractable bacterial populations are required to develop shorter and more effective treatment regimens. The benzene amide ether scaffold has activity against intracellular Mycobacterium tuberculosis, but low activity against extracellular, actively replicating M. tuberculosis. We determined that these molecules have bactericidal activity against non-replicating M. tuberculosis but not actively replicating bacteria. Exposure to compounds depleted ATP levels in non-replicating bacteria and increased the oxygen consumption rate; a subset of molecules led to the accumulation of intrabacterial reactive oxygen species. A comprehensive screen of M. tuberculosis strains identified a number of under-expressing strains as more sensitive to compounds under replicating conditions including QcrA and QcrB hypomorphs. We determined the global gene expression profile after compound treatment for both replicating and nutrient-starved M. tuberculosis. We saw compound-dependent changes in the expression of genes involved in energy metabolism under both conditions. Taken together, our data suggest that the scaffold targets respiration in M. tuberculosis.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tuberculosis
/
Mycobacterium tuberculosis
Límite:
Humans
Idioma:
En
Revista:
ACS Infect Dis
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos