气候变化领域集成服务门户(CCPortal): WhiB6 regulation of ESX-1 gene expression is controlled by a negative feedback loop in Mycobacterium marinum

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DOI	10.1073/pnas.1710167114
	WhiB6 regulation of ESX-1 gene expression is controlled by a negative feedback loop in Mycobacterium marinum
	Bosserman R.E.; Nguyen T.T.; Sanchez K.G.; Chirakos A.E.; Ferrell M.J.; Thompson C.R.; Champion M.M.; Abramovitch R.B.; Champion P.A.
发表日期	2017
ISSN	0027-8424
起始页码	E10772
结束页码	E10781
卷号	114 期号:50
英文摘要	ESX (ESAT-6 system) export systems play diverse roles across mycobacterial species. Interestingly, genetic disruption of ESX systems in different species does not result in an accumulation of protein substrates in the mycobacterial cell. However, the mechanisms underlying this observation are elusive. We hypothesized that the levels of ESX substrates were regulated by a feedback-control mechanism, linking the levels of substrates to the secretory status of ESX systems. To test this hypothesis, we used a combination of genetic, transcriptomic, and proteomic approaches to define export-dependent mechanisms regulating the levels of ESX-1 substrates in Mycobacterium marinum. WhiB6 is a transcription factor that regulates expression of genes encoding ESX-1 substrates. We found that, in the absence of the genes encoding conserved membrane components of the ESX-1 system, the expression of the whiB6 gene and genes encoding ESX-1 substrates were reduced. Accordingly, the levels of ESX-1 substrates were decreased, and WhiB6 was not detected in M. marinum strains lacking genes encoding ESX-1 components. We demonstrated that, in the absence of EccCb1, a conserved ESX-1 component, substrate gene expression was restored by constitutive, but not native, expression of the whiB6 gene. Finally, we found that the loss of WhiB6 resulted in a virulent M. marinum strain with reduced ESX-1 secretion. Together, our findings demonstrate that the levels of ESX-1 substrates in M. marinum are fine-tuned by negative feedback control, linking the expression of the whiB6 gene to the presence, not the functionality, of the ESX-1 membrane complex.
英文关键词	ESAT-6; ESX-1; Mycobacterium; Protein secretion; Regulation
语种	英语
scopus关键词	early secretory antigenic target 6; membrane protein; transcription factor; transcription factor WhiB6; unclassified drug; bacterial protein; transcription factor; Article; bacterial gene; bacterial secretion system; feedback system; gene expression regulation; Mycobacterium marinum; negative feedback; nonhuman; priority journal; protein secretion; signal transduction; gene expression regulation; genetics; metabolism; Mycobacterium marinum; physiological feedback; type VII secretion system; Bacterial Proteins; Feedback, Physiological; Gene Expression Regulation, Bacterial; Mycobacterium marinum; Transcription Factors; Type VII Secretion Systems
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/160566
作者单位	Bosserman, R.E., Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556, United States, Department of Microbiology and Molecular Genetics, University of Texas Health Science Center at Houston, Houston, TX 77030-1503, United States; Nguyen, T.T., Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556, United States, Eli Lilly and Company, Indianapolis, IN 46285, United States; Sanchez, K.G., Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556, United States; Chirakos, A.E., Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556, United States; Ferrell, M.J., Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556, United States; Thompson, C.R., Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556, United States; Champion, M.M., Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, United States; Abr...
推荐引用方式 GB/T 7714	Bosserman R.E.,Nguyen T.T.,Sanchez K.G.,et al. WhiB6 regulation of ESX-1 gene expression is controlled by a negative feedback loop in Mycobacterium marinum[J],2017,114(50).
APA	Bosserman R.E..,Nguyen T.T..,Sanchez K.G..,Chirakos A.E..,Ferrell M.J..,...&Champion P.A..(2017).WhiB6 regulation of ESX-1 gene expression is controlled by a negative feedback loop in Mycobacterium marinum.Proceedings of the National Academy of Sciences of the United States of America,114(50).
MLA	Bosserman R.E.,et al."WhiB6 regulation of ESX-1 gene expression is controlled by a negative feedback loop in Mycobacterium marinum".Proceedings of the National Academy of Sciences of the United States of America 114.50(2017).