control of cydb and glta1 expression by the senx3 regx3 two component regulatory system of mycobacterium tuberculosis控制cydb和glta1表达式由senx3 regx3结核分枝杆菌的两个组件的监管体系.pdf

Control of CydB and GltA1 Expression by the SenX3 RegX3 Two Component Regulatory System of Mycobacterium tuberculosis 1¤ 2 2 1,3 Gretta Roberts , Indumathi S. Vadrevu , Murty V. Madiraju , Tanya Parish * 1 Queen Mary University of London, Barts and the London School of Medicine and Dentistry, London, United Kingdom, 2 Biomedical Research, The University of Texas Health Center, Tyler, Texas, United States of America, 3 Infectious Disease Research Institute, Seattle, Washington, United States of America 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 mann