WhiB5, a transcriptional regulator that contributes to Mycobacterium tuberculosis virulence and reactivation.
Infect Immun
; 80(9): 3132-44, 2012 Sep.
Article
em En
| MEDLINE
| ID: mdl-22733573
ABSTRACT
The proteins belonging to the WhiB superfamily are small global transcriptional regulators typical of actinomycetes. In this paper, we characterize the role of WhiB5, a Mycobacterium tuberculosis protein belonging to this superfamily. A null mutant was constructed in M. tuberculosis H37Rv and was shown to be attenuated during both progressive and chronic mouse infections. Mice infected with the mutant had smaller bacillary burdens in the lungs but a larger inflammatory response, suggesting a role of WhiB5 in immunomodulation. Most interestingly, the whiB5 mutant was not able to resume growth after reactivation from chronic infection, suggesting that WhiB5 controls the expression of genes involved in this process. The mutant was also more sensitive than the wild-type parental strain to S-nitrosoglutathione (GSNO) and was less metabolically active following prolonged starvation, underscoring the importance of GSNO and starvation in development and maintenance of chronic infection. DNA microarray analysis identified 58 genes whose expression is influenced by WhiB5, including sigM, encoding an alternative sigma factor, and genes encoding the constituents of two type VII secretion systems, namely, ESX-2 and ESX-4.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Contexto em Saúde:
2_ODS3
Problema de saúde:
2_enfermedades_transmissibles
Assunto principal:
Fator sigma
/
Proteínas de Bactérias
/
Fatores de Virulência
/
Mycobacterium tuberculosis
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Infect Immun
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Itália