title: mosR, a novel transcriptional regulator of hypoxia and virulence in Mycobacterium tuberculosis.
abstract: 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.
authors: Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors: Bassam
authors: B
authors: Abomoelak
authors: Elizabeth A
authors: EA
authors: Hoye
authors: Jing
authors: J
authors: Chi
authors: Sarah A
authors: SA
authors: Marcus
authors: Francoise
authors: F
authors: Laval
authors: John P
authors: JP
authors: Bannantine
authors: Sarah K
authors: SK
authors: Ward
authors: Mamadou
authors: M
authors: Daffé
authors: Hong Di
authors: HD
authors: Liu
authors: Adel M
authors: AM
authors: Talaat
mesh_terms: 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*
chemical_list: D001426:Bacterial Proteins