ARS | Publication request: mosR, A Novel Transcriptional Regulator of Hypoxia and Virulence in Mycobacterium tuberculosis

Submitted to: Journal of Bacteriology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: July 20, 2009
Publication Date: October 1, 2009
Repository URL: http:////jb.asm.org/cgi/reprint/JB.00778-09v1?view=long&pmid=19648248
Citation: Abomoelak, B., Chi, J., Hoye, E.A., Bannantine, J.P., Talaat, A.M. 2009. MosR, A Novel Transcriptional Regulator of Hypoxia and Virulence in Mycobacterium tuberculosis. Journal of Bacteriology. 191(19):5941-5952.

Interpretive Summary: In this communication, we looked at a gene that regulates transcription or production of messenger RNA for all genes in mycobacterium. When this gene was removed or "knocked-out" it was shown to affect the transcription of over 150 genes! Many of these genes are important for the bacterium to survive in adverse conditions. One condition in particular is lack of oxygen. Finally, bacteria containing the knocked-out regulatory gene were shown to be much less able to survive in mice, indicating it is not virulent. These data have profound implications for pathogenesis and a better understanding of the biology of this significant pathogen.

Technical Abstract: Chronic tuberculosis represents a high-risk burden for one third of the world population. Previous microarray analysis of murine tuberculosis identified a novel transcriptional regulator encoded by rv0348 that could control the establishment of the chronic phase of tuberculosis. Disruption of the rv0348 sequence from the genome of the virulent strain of M. tuberculosis H37Rv revealed a global impact on the transcriptional profile of 163 genes including induction of the mammalian cell entry operon (mce1) and the repression of a significant number of genes involved in hypoxia and starvation responses. When the M. tb-derived Rv0348 protein was expressed in M. smegmatis, it was shown to repress some members of the dosR regulon that are involved in hypoxia and to induce mce1 among other genes. In BALB/c mice, the colonization levels of the Delta rv0348 strain were significantly lower than the wild-type strain of M. tb, suggesting its attenuation and the involvement of rv0348 in M. tb virulence. Taken together, our analyses indicated that the rv0348 gene encodes a novel transcriptional factor that regulates several gene operons involved in mycobacterial survival during infection; hence we propose that rv0348 be renamed mosR for regulator of mycobacterial operons of survival.