Abstract
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.
Highlights
Mycobacterium tuberculosis is a sophisticated pathogen with a long and complex association with its human host
SenX3-RegX3 two component regulatory system is required for the full virulence of M. tuberculosis in both macrophage and murine infection models [5,7]
We were interested in the role of the SenX3 RegX3 two component regulatory system during growth under different oxygen tensions
Summary
Mycobacterium tuberculosis is a sophisticated pathogen with a long and complex association with its human host. In contrast to many infectious agents, M. tuberculosis exhibits a tendency to remain latent or persistent in the target organ, the lung, for decades before reactivation leads to symptomatic disease. The capacity of this organism to establish both primary and secondary infections and to maintain its presence within the lung granuloma is predicted to be dependent on its ability to respond to changes in the environment. The recognition of external or internal conditions and their integration into global gene expression patterns is an essential requirement of the bacteria in their own unique pathogenic lifestyle. Exposure to a specific external stimulus usually leads to a defined pattern of gene expression which is often mediated by global gene regulators. M. tuberculosis has nine complete two component systems and each is predicted to control a subset of the genome, the regulon, in response to a single stimulus
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