Abstract
Gene regulatory networks used by Mycobacterium tuberculosis (Mtb) during infection include many genes of unknown function, confounding efforts to determine their roles in Mtb biology. Rv1265 encodes a conserved hypothetical protein that is expressed during infection and in response to elevated levels of cyclic AMP. Here, we report that Rv1265 is a novel auto-inhibitory ATP-binding transcription factor that upregulates expression of the small non-coding RNA Mcr11, and propose that Rv1265 be named ATP-binding mcr11 regulator (AbmR). AbmR directly and specifically bound DNA, as determined by electrophoretic mobility shift assays, and this DNA-binding activity was enhanced by AbmR's interaction with ATP. Genetic knockout of abmR in Mtb increased abmR promoter activity and eliminated growth phase-dependent increases in mcr11 expression during hypoxia. Mutagenesis identified arginine residues in the carboxy terminus that are critical for AbmR's DNA-binding activity and gene regulatory function. Limited similarity to other DNA- or ATP-binding domains suggests that AbmR belongs to a novel class of DNA- and ATP-binding proteins. AbmR was also found to form large organized structures in solution and facilitate the serum-dependent association of Mtb with human lung epithelial cells. These results indicate a potentially complex role for AbmR in Mtb biology.