A Novel TetR-Like Transcriptional Regulator Is Induced in Acid-Nitrosative Stress and Controls Expression of an Efflux Pump in Mycobacteria.

has the ability to survive inside macrophages under acid-nitrosative stress. and its ortholog in , are induced on exposure to acid-nitrosative stress. Both genes are annotated as TetR transcriptional regulators, a family of proteins that regulate a wide range of cellular activities, including multidrug resistance, carbon catabolism and virulence. Here, we demonstrate that is co-transcribed with the upstream genes and , encoding efflux pump components. RTq-PCR and GFP-reporter assays showed that the gene cluster, and the orthologous region in (), was up-regulated in a null mutant, suggesting that acts as a repressor, typical of this family of regulators. We further defined the regulon using genome-wide transcriptional profiling and used reporter assays to confirm that the promoter was induced under acid-nitrosative stress. A putative 36 bp regulatory motif was identified upstream of the gene clusters in both and and purified recombinant MSMEG_3765 protein was found to bind to DNA fragments containing this motif from both and upstream regulatory regions. These results suggest that the TetR repressor controls expression of an efflux pump with an, as yet, undefined role in the mycobacterial response to acid-nitrosative stress.