CsrA controls ToxR levels by increasing the stability and translation of mRNA.

Intestinal colonization and virulence factor production in response to environmental cues is mediated through several regulatory factors in , including the highly conserved RNA-binding global regulatory protein CsrA. We have shown previously that CsrA increases synthesis of the virulence-associated transcription factor ToxR in response to specific amino acids (NRES) and is required for the virulence of in the infant mouse model of cholera. In this study, we mapped the 5' untranslated region (5' UTR) of and showed that CsrA can bind directly to an RNA sequence encompassing the 5' UTR, indicating that the regulation of ToxR levels by CsrA is direct.

CsrA controls ToxR levels by increasing the stability and translation of mRNA.

Unlabelled: Regulation of colonization and virulence factor production in response to environmental cues is mediated through several regulatory factors in , including the highly conserved RNA-binding global regulatory protein CsrA. We have shown previously that CsrA increases synthesis of the virulence-associated transcription factor ToxR in response to specific amino acids (NRES) and is required for the virulence of in the infant mouse model of cholera. In this study, we mapped the 5' untranslated region (5' UTR) of and showed that CsrA can bind directly to an RNA sequence encompassing the 5' UTR, indicating that the regulation of ToxR levels by CsrA is direct.

Structural Insights into Regulation of Vibrio Virulence Gene Networks.

One of the best studied aspects of pathogenic Vibrios are the virulence cascades that lead to the production of virulence factors and, ultimately, clinical outcomes. In this chapter, we will examine the regulation of Vibrio virulence gene networks from a structural and biochemical perspective. We will discuss the recent research into the numerous proteins that contribute to regulating virulence in Vibrio spp such as quorum sensing regulator HapR, the transcription factors AphA and AphB, or the virulence regulators ToxR and ToxT.

An Enantiodefined Conformationally Constrained Fatty Acid Mimetic and Potent Inhibitor of ToxT.

The chiral conformation that palmitoleic acid takes when it is bound to ToxT, the master regulator of virulence genes in the bacterial pathogen , was used as inspiration to design a novel class of fatty acid mimetics. The best mimetic, based on a chiral hydrindane, was found to be a potent inhibitor of this target. The synthetic chemistry that enabled these studies was based on the sequential use of a stereoselective annulative cross-coupling reaction and dissolving metal reduction to establish the C13 and C9 stereocenters, respectively.

Structure of the master regulator Rns reveals an inhibitor of enterotoxigenic Escherichia coli virulence regulons.

Enteric infections caused by the gram-negative bacteria enterotoxigenic Escherichia coli (ETEC), Vibrio cholerae, Shigella flexneri, and Salmonella enterica are among the most common and affect billions of people each year. These bacteria control expression of virulence factors using a network of transcriptional regulators, some of which are modulated by small molecules as has been shown for ToxT, an AraC family member from V. cholerae.