A Conserved Switch Controls Virulence, Sporulation, and Motility in .

Spore formation is required for environmental survival and transmission of the human enteropathogenic . In all bacterial spore formers, sporulation is regulated through activation of the master response regulator, Spo0A. However, the factors and mechanisms that directly regulate Spo0A activity are not defined. In the well-studied species, Spo0A is directly inactivated by Spo0E, a small phosphatase. To understand Spo0E function in , we created a null mutation of the ortholog and assessed sporulation and physiology. The mutant produced significantly more spores, demonstrating Spo0E represses sporulation. Unexpectedly, the mutant also exhibited increased motility and toxin production, and enhanced virulence in animal infections. We uncovered that Spo0E interacts with both Spo0A and the toxin and motility regulator, RstA. Direct interactions between Spo0A, Spo0E, and RstA constitute a previously unknown molecular switch that coordinates sporulation with motility and toxin production. Reinvestigation of Spo0E function in revealed that Spo0E induced motility, demonstrating Spo0E regulation of motility and sporulation among divergent species. Further, we found that Spo0E orthologs are widespread among prokaryotes, suggesting that Spo0E performs conserved regulatory functions in diverse bacteria.