Integration of a complex regulatory cascade involving the SirA/BarA and Csr global regulatory systems that controls expression of the Salmonella SPI-1 and SPI-2 virulence regulons through HilD
Article first published online: 12 MAY 2011
© 2011 Blackwell Publishing Ltd
Volume 80, Issue 6, pages 1637–1656, June 2011
How to Cite
Martínez, L. C., Yakhnin, H., Camacho, M. I., Georgellis, D., Babitzke, P., Puente, J. L. and Bustamante, V. H. (2011), Integration of a complex regulatory cascade involving the SirA/BarA and Csr global regulatory systems that controls expression of the Salmonella SPI-1 and SPI-2 virulence regulons through HilD. Molecular Microbiology, 80: 1637–1656. doi: 10.1111/j.1365-2958.2011.07674.x
- Issue published online: 14 JUN 2011
- Article first published online: 12 MAY 2011
- Accepted manuscript online: 26 APR 2011 03:45AM EST
- Accepted 18 April, 2011.
Salmonella pathogenicity islands 1 and 2 (SPI-1 and SPI-2) play key roles in the pathogenesis of Salmonella enterica. Previously, we showed that when Salmonella grows in Luria–Bertani medium, HilD, encoded in SPI-1, first induces the expression of hilA, located in SPI-1, and subsequently of the ssrAB operon, located in SPI-2. These genes code for HilA and the SsrA/B two-component system, the positive regulators of the SPI-1 and SPI-2 regulons respectively. In this study, we demonstrate that CsrA, a global regulatory RNA binding protein, post-transcriptionally regulates hilD expression by directly binding near the Shine–Dalgarno and translation initiation codon sequences of the hilD mRNA, preventing its translation and leading to its accelerated turnover. Negative regulation is counteracted by the global SirA/BarA two-component system, which directly activates the expression of CsrB and CsrC, two non-coding regulatory RNAs that sequester CsrA, thereby preventing it from binding to its target mRNAs. Our results illustrate the integration of global and specific regulators into a multifactorial regulatory cascade controlling the expression of virulence genes acquired by horizontal transfer events.