Transcriptional activation of the Mycobacterium tuberculosis virulence ‐associated small RNA MTS1338 by the response regulators DosR and PhoP

MTS1338 is an infection-induced small RNA found in pathogenic mycobacterial strains. It is highly accumulated in response to numerous stresses. Herein, we investigated how MTS1338 is regulated at the transcriptional level. Our findings reveal the interplay of DosR (a mycobacterial dormancy regulator) and PhoP (which regulates low pH-inducible genes) at the promoter region of theMTS1338 gene during transcriptional activation. MTS1338, a distinctive small RNA in pathogenic mycobacteria, plays a crucial role in host –pathogen interactions during infection. Mycobacterial cells encounter heterogeneous stresses in macrophages, which highly upregulate MTS1338. A dormancy regulatory factor DosR regulates the intracellular abundance of MTS1338. Herein, we investigated the interplay of DosR and a low pH-inducible ge ne regulator PhoP binding to the MTS1338 promoter. We identified that DosR strongly binds to two regions upstream of the MTS1338 gene. The proximal region possesses a threefold higher affinity than the distal site, but the presence of both regions increased the affinity for DosR by>  10-fold. PhoP did not bind to the MTS1338 gene but binds to the DosR-bound MTS1338 gene, suggesting a concerted mechanism for MTS1338 expression.
Source: FEBS Letters - Category: Biochemistry Authors: Tags: Research Letter Source Type: research