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Two component regulatory systems are used widely by bacteria to coordinate changes in global gene expression profiles in response to environmental signals. The SenX3-RegX3 two component system of  Mycobacterium tuberculosis  has previously been shown to play a role in virulence and phosphate-responsive control of gene expression. We demonstrate that expression of SenX3-RegX3 is controlled in response to growth conditions, although the absolute changes are small. Global gene expression profiling of a RegX3 deletion strain and wild-type strain in different culture conditions (static, microaerobic, anaerobic), as well as in an over-expressing strain identified a number of genes with changed expression patterns. Among those were genes previously identified as differentially regulated in aerobic culture, including  ald  (encoding alanine dehydrogenase)  cyd ,encoding a subunit of the cytochrome D ubiquinol oxidase, and  gltA1 , encoding a citrate synthase. Promoter activity in the upstream regions of both  cydB  and  gltA1  was altered in the RegX3 deletion strain. DNA-binding assays confirmed that RegX3 binds to the promoter regions of  ald ,  cydB  and  gltA1  in a phosphorylation-dependent manner. Taken together these data suggest a direct role for the SenX-RegX3 system in modulating expression of aerobic respiration, in addition to its role during phosphate limitation.

Control of CydB and GltA1 Expression by the SenX3 RegX3 Two Component Regulatory System of Mycobacterium tuberculosis