MymA operon of Mycobacterium tuberculosis: its regulation and importance in the cell envelope

Abstract

Mycobacterium tuberculosis faces various stressful conditions inside the host and responds to them through a coordinated regulation of gene expression. We had previously reported identification of the virS gene of M. tuberculosis ( Rv3082c) belonging to the AraC family of transcriptional regulators. In the current study, we show that the seven genes ( Rv3083–Rv3089) which are present divergently to virS ( Rv3082c) constitute an operon designated the mymA operon. Further investigation on the regulation of this operon showed that transcription of the mymA operon is dependent on the presence of VirS protein. A four-fold induction of the mymA operon promoter occurs specifically in wild-type M. tuberculosis and not in the virS mutant of M. tuberculosis (MtbΔ virS) when exposed to acidic pH. Expression of the mymA operon was also induced in infected macrophages by 10-fold over a 6-day period. To gain an insight into the function of the proteins encoded by this operon, we carried out a bioinformatic analysis, which suggested the involvement of these proteins in the modification of fatty acids required for cell envelope. This was supported by altered colony morphology and cell envelope structure displayed by the virS mutant of M. tuberculosis (MtbΔ virS).