Identification of CsrC and Characterization of Its Role in Epithelial Cell Invasion in Salmonella enterica Serovar Typhimurium

The csr regulatory system ofSalmonella regulates the expression of the genes ofSalmonella pathogenicity island 1 (SPI1) required for the invasion of epithelial cells. This system consists of the posttranscriptional regulator CsrA and an untranslated regulatory RNA, CsrB, that opposes the action of CsrA. Here we identify and characterize the role of a second regulatory RNA, CsrC, whose ortholog was discovered previously inEscherichia coli . We show that a mutant ofcsrC has only mild defects in invasion and the expression of SPI1 genes, as does a mutant ofcsrB , but that a doublecsrB csrC mutant is markedly deficient in these properties, suggesting that the two regulatory RNAs play redundant roles in the control of invasion. We further show that CsrC, like CsrB, is controlled by the BarA/SirA two-component regulator but that acsrB csrC mutant exhibits a loss of invasion equivalent to that of abarA orsirA mutant, indicating that much of the effect of BarA/SirA on invasion functions through its control of CsrB and CsrC. In addition to their control by BarA/SirA, each regulatory RNA is also controlled by other components of the csr system. The loss ofcsrB was found to increase the level of CsrC by sevenfold, while the loss ofcsrC increased CsrB by nearly twofold. Similarly, the overexpression ofcsrA increased CsrC by nearly 11-fold and CsrB by 3-fold and also significantly increased the stability of both RNAs.