Pleiotropic effects on E. coli physiology of the AraC-like regulator from prophage origin, AppY

Abstract

Bacterial genome diversity is largely due to prophages, which are viral genomes integrated into the genomes of bacteria. Most prophage genes are silent, but those that are expressed can provide unexpected properties to their host. Using as a model E. coli K-12, that carries 9 defective prophages in its genome, we aimed at highlighting the impact of viral genes on host physiology. We focused our work on AppY, a transcriptional regulator encoded on the DLP12 prophage. By performing RNA-Seq experiments, we showed that AppY production modulates the expression of more than 200 genes; among them, 13 were identified by ChIP-Seq as direct AppY targets. AppY directly and positively regulates several genes involved in the acid stress response including the master regulator gene gadE, but also nhaR and gadY, two genes involved in biofilm formation. Moreover, AppY indirectly and negatively impacts bacterial motility by favouring the degradation of FlhDC, the master regulator of the flagella biosynthesis. As a consequence of these regulatory effects, AppY increased acid stress resistance and biofilm formation while also causing a strong defect in motility. We therefore demonstrate here that AppY is a central regulator from phage origin that controls the expression of bacterial master regulators to provide benefits to E. coli under stress conditions. Our research shed light on the importance to consider the genetic dialogue occurring between prophages and bacteria to fully understand bacterial physiology.