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Summary  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  A TP‐ b inding    m cr11    r egulator (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.

molecular microbiology

AbmR (Rv1265) is a novel transcription factor of  Mycobacterium tuberculosis  that regulates host cell association and expression of the non‐coding small RNA Mcr11