Characterization of SlyA in Shigella flexneri Identifies a Novel Role in Virulence

The SlyA transcriptional regulator has important roles in the virulence and pathogenesis of several members of the Enterobacteriaceae family, including Salmonella enterica serovar Typhimurium and Escherichia coli. Despite the identification of the slyA gene in Shigella flexneri nearly 2 decades ago, as well as the significant conservation of SlyA among enteric bacteria, the role of SlyA in Shigella remains unknown. The genes regulated by SlyA in closely related organisms often are absent from or mutated inS. flexneri, and consequently many described SlyA-dependent phenotypes are not present. By characterizing the expression of slyA and determining its ultimate effect in this highly virulent organism, we postulated that novel SlyA-regulated virulence phenotypes would be identified. In this study, we report the first analysis of SlyA in Shigella and show that (i) the slyA gene is transcribed and ultimately translated into protein, (ii) slyA promoter activity is maximal during stationary phase and is negatively autoregulated and positively regulated by the PhoP response regulator, (iii) the exogenous expression of slyA rescues transcription and virulence-associated deficiencies during virulence-repressed conditions, and (iv) the absence of slyA significantly decreases acid resistance, demonstrating a novel and important role in Shigella virulence. Cumulatively, our study illustrates unexpected parallels between the less conserved S. flexneri and S Typhimurium slyA promoters as well as a unique role for SlyA in Shigella virulence that has not been described previously in any closely related organism.