An ArsR-like transcriptional factor recognizes a conserved sequence motif and positively regulates the expression of phoP in mycobacteria

Abstract

Transcriptional regulation plays a critical role during the infection of Mycobacterium tuberculosis, the causative agent of tuberculosis. A two-component system, PhoPR, is clearly involved in the regulation of pathogenic virulence and persistence. However, the regulatory mechanism, as well as the regulator, of the phoPR operon remains uncharacterized in M. tuberculosis and its related species thus far. In the present study, we characterize an ArsR transcriptional factor, corresponding to Rv2034 and Ms6762 in M. tuberculosis and Mycobacterium smegmatis, respectively, as the first regulator of phoP in both mycobacterial species. The interaction between ArsR regulator and target promoters is conserved in these two mycobacterial species, and an inverted repeat sequence motif is successfully mapped out for the recognition of ArsR. Utilizing lacZ reporter genes and overexpression analysis, the ArsR regulator is shown to positively regulate the expression of phoP in M. smegmatis, different from most ArsR family regulators generally as a repressor. The current study establishes a direct link between the ArsR transcriptional factor and the regulation of phoP in mycobacteria. Our findings imply that ArsR may be involved in the pathogenesis of M. tuberculosis through its regulation of the phoPR operon.