mosR, a novel transcriptional regulator of hypoxia and virulence in Mycobacterium tuberculosis.
Latent tuberculosis represents a high-risk burden for one-third of the world population. Previous analysis of murine tuberculosis identified a novel transcriptional regulator encoded by Rv0348 that could control the establishment of persistent tuberculosis. Disruption of the Rv0348 gene from the genome of the virulent H37Rv strain of Mycobacterium tuberculosis revealed a global impact on the transcriptional profiles of 163 genes, including induction of the mammalian cell entry (mce1) operon and the repression of a significant number of genes involved in hypoxia and starvation responses. Nonetheless, gel shift assays did not reveal direct binding between Rv0348 and a set of regulated promoters, suggesting an indirect regulatory role. However, when expressed in Mycobacterium smegmatis, the Rv0348 transcripts were significantly responsive to different levels of hypoxia and the encoded protein was shown to regulate genes involved in hypoxia [e.g., Rv3130c (tgs1)] and intracellular survival (e.g., mce1), among other genes. Interestingly, the colonization level of the DeltamosR mutant strain was significantly lower than that of the wild-type strain of M. tuberculosis, suggesting its attenuation in the murine model of tuberculosis. Taken together, our analyses indicated that the Rv0348 gene encodes a novel transcriptional factor that regulates several operons involved in mycobacterial survival, especially during hypoxia; hence, we propose that Rv0348 be renamed mosR for regulator of mycobacterial operons of survival.
Abomoelak
Bassam
B
Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA.
Hoye
Elizabeth A
EA
Chi
Jing
J
Marcus
Sarah A
SA
Laval
Francoise
F
Bannantine
John P
JP
Ward
Sarah K
SK
Daffé
Mamadou
M
Liu
Hong Di
HD
Talaat
Adel M
AM
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D024202:Electrophoretic Mobility Shift Assay; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics / Q000502:physiology; D015151:Immunoblotting; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000378:metabolism* / Q000472:pathogenicity; D009876:Operon / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014158:Transcription, Genetic / Q000235:genetics*; D014376:Tuberculosis / Q000235:genetics / Q000382:microbiology; D014774:Virulence / Q000235:genetics*
D001426:Bacterial Proteins