The prophage-encoded transcriptional regulator AppY has pleiotropic effects on E. coli physiology

PLoS Genet. 2023 Mar 17;19(3):e1010672. doi: 10.1371/journal.pgen.1010672. eCollection 2023 Mar.

Abstract

Bacterial genome diversity is influenced by prophages, which are viral genomes integrated into the bacterial chromosome. 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 genes encoded by prophages 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, 11 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 important for biofilm formation. Moreover, AppY indirectly and negatively impacts bacterial motility by favoring the degradation of FlhDC, the master regulator of the flagella biosynthesis. As a consequence of these regulatory effects, AppY increases acid stress resistance and biofilm formation while also causing a strong defect in motility. Our research shed light on the importance to consider the genetic interactions occurring between prophages and bacteria to fully understand bacterial physiology. It also highlights how a prophage-encoded transcriptional regulator integrates in a complex manner into the host regulatory network and how it benefits its host, allowing it to cope with changing environmental conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacteria / genetics
  • Escherichia coli Proteins* / genetics
  • Escherichia coli Proteins* / metabolism
  • Escherichia coli* / genetics
  • Escherichia coli* / metabolism
  • Genome, Bacterial / genetics
  • Prophages / genetics

Substances

  • Escherichia coli Proteins

Grants and funding

N.D., N.G., Y.D., M.A. and A.B. work was funded by the Centre National de la Recherche Scientifique (CNRS, http://www.cnrs.fr) and Aix Marseille Univ (AMU, https://www.univ-amu.fr). A. B. was supported by a grant from the Agence Nationale de la Recherche (ANR-18-CE12-0024-01). N.D. is the recipient of a French Ministry fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.