ΣE controlled regulation of porin OmpU in Vibrio cholerae. Issue 6 (25th January 2021)

• Record Type: Journal Article
• Authors: Pennetzdorfer, Nina; Höfler, Thomas; Wölflingseder, Martina; Tutz, Sarah; Schild, Stefan; Reidl, Joachim
• Is Part Of: Molecular microbiology. Volume 115:Issue 6(2021)
• Page Start: 1244
• Page End: 1261
• Publication Date: 2021-01-25
• Subjects: OmpU -- RpoE -- stress response -- ToxR -- transcriptional regulation and Vibrio cholerae; Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.14669
• Languages: English
• ISSNs: 0950-382X

Abstract

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 σ E ‐pathway in V . cholerae . To understand the mechanism by which the sigma factor σ E regulates OmpU synthesis, we performed transcription studies using ompU reporter fusions and immunoblot analysis. Our data revealed an increase in ompU promoter activity in Δ rpoE strains, as well as in a Δ ompU background, indicating a negative feedback regulation circuit of ompU expression. This regulation seems necessary, since elevated lethality rates of Δ rpoE strains occur upon ompU overexpression. Manipulation of OmpU's C‐terminal portion revealed its relevance for protein stability and potency of σ E release. Furthermore, Δ rpoE 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 σ E on ompU regulation, which is critical to the pathogen's intestinal survival. Abstract : A regulatory circuit indicates the interplay between the major outer membrane porin OmpU, periplasmic stress stimuli and the σE response pathway in Vibrio cholerae. This study reveals a negative feedback regulation resulting in fine‐tuning of the ompU expression level, balancing stress response and survival. Putative factor(s) operating on the negative feedback regulation on ompU expression is shown in burgundy colour.