Dissectingpsalocus regulation inYersinia pestis

The pH 6 antigen ofYersinia pestisis a virulence factor that is expressed in response to high temperature (37 °C) and low pH (6.0). Previous studies have implicated the PsaE and PsaF regulators in the temperature- and pH-dependent regulation ofpsaA. Here, we show that PsaE levels are themselves controlled by pH and temperature, explaining the regulation ofpsaA. We identify hundreds of binding sites for PsaE across theY. pestisgenome, with the majority of binding sites located in intergenic regions. However, we detect direct regulation of very few genes by PsaE, suggesting either that most binding sites are non-regulatory, or that they require additional environmental cues. We also identify the precise binding site for PsaE that is required for temperature- and pH-dependent regulation ofpsaA. Thus, our data reveal the critical function that PsaE plays in regulation ofpsaA, and suggest that PsaE may have many additional regulatory targets.