WhiB5, a transcriptional regulator that contributes to Mycobacterium tuberculosis virulence and reactivation.
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.
Department of Histology, Microbiology and Medical Biotechnologies, University of Padua, Padua, Italy.
Stefano
S
Casonato
Axel
A
Cervantes Sánchez
Hirohito
H
Haruki
Monica
M
Rengifo González
Roberta
R
Provvedi
Elisa
E
Dainese
Thomas
T
Jaouen
Susanne
S
Gola
Estela
E
Bini
Miguel
M
Vicente
Kai
K
Johnsson
Daniela
D
Ghisotti
Giorgio
G
Palù
Rogelio
R
Hernández-Pando
Riccardo
R
Manganelli
D000818:Animals; D058491:Bacterial Load; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D017353:Gene Deletion; D020869:Gene Expression Profiling; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D046228:Microarray Analysis; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000472:pathogenicity*; D012808:Sigma Factor / Q000235:genetics / Q000378:metabolism*; D014397:Tuberculosis, Pulmonary / Q000382:microbiology / Q000473:pathology; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
D001426:Bacterial Proteins; D012808:Sigma Factor; D037521:Virulence Factors