The RNA Chaperone Hfq Is Essential for Virulence and Modulates the Expression of Four Adhesins in Yersinia enterocolitica.

Tamara Katharina Kakoschke,Kristin Adler,Sara Carina Kakoschke,Catharina Zeuzem,Ombeline Rossier,Hicham Bouabe,Jürgen Heesemann

doi:10.1038/srep29275

Abstract

In Enterobacteriaceae, the RNA chaperone Hfq mediates the interaction of small RNAs with target mRNAs, thereby modulating transcript stability and translation. This post-transcriptional control helps bacteria adapt quickly to changing environmental conditions. Our previous mutational analysis showed that Hfq is involved in metabolism and stress survival in the enteropathogen Yersinia enterocolitica. In this study we demonstrate that Hfq is essential for virulence in mice and influences production of surface pathogenicity factors, in particular lipopolysaccharide and adhesins mediating interaction with host tissue. Hfq inhibited the production of Ail, the Ail-like protein OmpX and the MyfA pilin post-transcriptionally. In contrast Hfq promoted production of two major autotransporter adhesins YadA and InvA. While protein secretion in vitro was not affected, hfq mutants exhibited decreased protein translocation by the type III secretion system into host cells, consistent with decreased production of YadA and InvA. The influence of Hfq on YadA resulted from a complex interplay of transcriptional, post-transcriptional and likely post-translational effects. Hfq regulated invA by modulating the expression of the transcriptional regulators rovA, phoP and ompR. Therefore, Hfq is a global coordinator of surface virulence determinants in Y. enterocolitica suggesting that it constitutes an attractive target for developing new antimicrobial strategies.

Highlights

Quick adaptation to changing environmental conditions is key to a pathogen’s success in the infected host
Using an antibody specific for E. coli OmpX40, we could detect a single band with the expected size in extracts of Y. enterocolitica (Fig. 1a)
We demonstrated the importance of the RNA chaperone Hfq for the virulence of Y. enterocolitica

Summary

Introduction

Quick adaptation to changing environmental conditions is key to a pathogen’s success in the infected host. Enteropathogenic yersiniae possess several proteins exposed at their surface that are crucial for virulence in the mouse model of yersiniosis They include three non-fimbrial adhesins InvA, YadA and Ail which promote adherence to host cells[2,3]. Upon a switch from 27 °C (optimal growth temperature) to 37 °C (host temperature), the bacteria remodel their surface: (i) they downregulate production of flagella, InvA, and the transfer of O-Ag onto the LPS10–12 and (ii) they increase production of YadA, Ail, Ysc T3SS and the LpxR-mediated LPS modifications[4,8,9,13,14]. In Salmonella enterica serovar Typhimurium Hfq impacts the expression of 10–20% genes in the genome and interacts with 30% of the identified Hfq-dependent transcripts[28,29], thereby constituting a global regulatory hub

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