σ^E controlled regulation of porin OmpU in Vibrio cholerae

Abstract

Bile resistance is essential for enteric pathogens, as exemplified by Vibrio cholerae, the causative agent of cholera. The outer membrane porin OmpU confers bacterial survival and colonization advantages in the presence of host‐derived antimicrobial peptides as well as bile. Expression of ompU is controlled by the virulence regulator ToxR. rpoE knockouts are accompanied by suppressor mutations causing ompU downregulation. Therefore, OmpU constitutes an intersection of the ToxR regulon and the σE‐pathway in V. cholerae. To understand the mechanism by which the sigma factor σE regulates OmpU synthesis, we performed transcription studies using ompU reporter fusions and immunoblot analysis. Our data revealed an increase in ompU promoter activity in ΔrpoE strains, as well as in a ΔompU background, indicating a negative feedback regulation circuit of ompU expression. This regulation seems necessary, since elevated lethality rates of ΔrpoE strains occur upon ompU overexpression. Manipulation of OmpU’s C‐terminal portion revealed its relevance for protein stability and potency of σE release. Furthermore, ΔrpoE strains are still capable of elevating OmpU levels under membrane stress conditions triggered by the bile salt sodium deoxycholate. This study provides new details about the impact of σE on ompU regulation, which is critical to the pathogen’s intestinal survival.

Outer membrane vesicles and the outer membrane protein OmpU govern Vibrio cholerae biofilm matrix assembly

“…OmpU is well-conserved across Vibrio species and is the most abundant and best-studied OMP in V. cholerae ( 56 ). OmpU confers resistance to host-derived antimicrobial peptides, and bile connects envelope stress to activation of the σE pathway, facilitates the adhesion of V. cholerae to mammalian cells, and modulates host immune responses ( 45 , 57 – 59 ). We found that OmpU regulates biofilm matrix production, expanding the role OmpU plays in V. cholerae cellular processes.…”

Non-O1/Non-O139 Vibrio cholerae—An Underestimated Foodborne Pathogen? An Overview of Its Virulence Genes and Regulatory Systems Involved in Pathogenesis

“…OmpU is widely present in NOVC [9,57,58] and should have the same response to the presence of bile. Due to its smaller channel size which prevents the influx of bile salts into the bacterial cell, the porin OmpU will be replaced instead of a larger channel porin such as OmpT [45,59].…”