An IclR like protein from mycobacteria regulates leuCD operon and induces dormancy-like growth arrest in Mycobacterium smegmatis

leuCD operonencodes isopropylmalate isomerase(IPMI), an essential enzyme in leucinebiosynthesis. Leucinebiosynthesis is one of the essential metabolic pathways for Mycobacterium tuberculosis survival inside the macrophage. In this study, we identified an IclR like transcription regulator, Rv2989 involved in regulation of leuCD expression. Further, we have shown that the Rv2989 binding site overlaps with the promoter region of leuCD , indicating its direct involvement in the regulation of this operon. Ectopic expressionof Rv2989 in M. smegmatis induced growth arrest with significantly decreased levels of leuCD transcript. However, supplementation with leucinecould not reverse the growth arrest, suggesting the involvement of Rv2989 in the regulation of other essential pathways. Growth-arrested cells were elongated, had lost acid fastnessand accumulated lipid dropletssimilar to a dormancy-like state. In conclusion, the Rv2989 expression has pleiotropiceffects on M. smegmatis. It negatively regulates leuCD operonand induces dormancy-like growth arrest.