Lung microenvironments harbor Mycobacterium tuberculosis phenotypes with distinct treatment responses.
Antimicrob Agents Chemother
; 67(9): e0028423, 2023 09 19.
Article
em En
| MEDLINE
| ID: mdl-37565762
ABSTRACT
Tuberculosis lung lesions are complex and harbor heterogeneous microenvironments that influence antibiotic effectiveness. Major strides have been made recently in understanding drug pharmacokinetics in pulmonary lesions, but the bacterial phenotypes that arise under these conditions and their contribution to drug tolerance are poorly understood. A pharmacodynamic marker called the RS ratio® quantifies ongoing rRNA synthesis based on the abundance of newly synthesized precursor rRNA relative to mature structural rRNA. Application of the RS ratio in the C3HeB/FeJ mouse model demonstrated that Mycobacterium tuberculosis populations residing in different tissue microenvironments are phenotypically distinct and respond differently to drug treatment with rifampin, isoniazid, or bedaquiline. This work provides a foundational basis required to address how anatomic and pathologic microenvironmental niches may contribute to long treatment duration and drug tolerance during the treatment of human tuberculosis.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tuberculose
/
Mycobacterium tuberculosis
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Antimicrob Agents Chemother
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos