WhiB6 regulation of ESX-1 gene expression is controlled by a negative feedback loop in Mycobacterium marinum

作者：Rachel E. Bosserman, Tiffany Nguyen, Kevin Sanchez, Alexandra E. Chirakos, Micah J. Ferrell, Cristal Reyna Thompson, Matthew M. Champion, Robert B. Abramovitch, Patricia A. Champion · 发表于：Proceedings of the National Academy of Sciences · 年份：2017 · DOI：10.1073/pnas.1710167114 · 被引用次数：63 · 研究领域：Tuberculosis Research and Epidemiology、Mycobacterium research and diagnosis、RNA and protein synthesis mechanisms

Significance Mycobacteria use ESX systems to transport protein substrates across the cytoplasmic membrane. The ESX-1 system is required for mycobacterial pathogenesis in Mycobacterium tuberculosis ( M. tb ), the cause of tuberculosis (TB). Differences in the expression of genes encoding ESX substrates directly impacts M. tb transmission and virulence. Deletion of genes encoding ESX exporters results in reduced levels of ESX substrates in mycobacteria. Here, we define a fundamental mechanism of regulation of ESX-1 substrates in M. marinum , a pathogenic mycobacterial species and a model for M. tb . We demonstrate that the transcriptional regulation of genes encoding ESX-1 substrates is linked to the presence or absence of the ESX-1 exporter. These findings provide insight into how substrate levels are intricately controlled in mycobacteria.