The RyfA small RNA regulates oxidative and osmotic stress responses and virulence in uropathogenic Escherichia coli.

Hicham Bessaiah,Julien Van Grevenynghe,Sébastien Houle,Éric Massé,Jacques Bernier,Merve Kulbay,Pravil Pokharel,Charles M Dozois,Charles Sasseville,Hajer Habouria,Hamza Loucif,Eric Oswald

doi:10.1371/journal.ppat.1009617

Hicham Bessaiah, Julien Van Grevenynghe + Show 10 more

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https://doi.org/10.1371/journal.ppat.1009617

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Abstract

Urinary tract infections (UTIs) are a common bacterial infectious disease in humans, and strains of uropathogenic Escherichia coli (UPEC) are the most frequent cause of UTIs. During infection, UPEC must cope with a variety of stressful conditions in the urinary tract. Here, we demonstrate that the small RNA (sRNA) RyfA of UPEC strains is required for resistance to oxidative and osmotic stresses. Transcriptomic analysis of the ryfA mutant showed changes in expression of genes associated with general stress responses, metabolism, biofilm formation and genes coding for cell surface proteins. Inactivation of ryfA in UPEC strain CFT073 decreased urinary tract colonization in mice and the ryfA mutant also had reduced production of type 1 and P fimbriae (pili), adhesins which are known to be important for UTI. Furthermore, loss of ryfA also reduced UPEC survival in human macrophages. Thus, ryfA plays a key regulatory role in UPEC adaptation to stress, which contributes to UTI and survival in macrophages.

Highlights

Urinary tract infections (UTIs) are one of the most prevalent bacterial infections, affecting millions of people each year [1]
Small regulatory RNAs play a critical role in bacterial adaptation, physiology, and metabolism
We investigated the role of the small RNA ryfA in uropathogenic E. coli, by using genetic, molecular and cell culture approaches, and mouse infection models

Summary

Introduction

Urinary tract infections (UTIs) are one of the most prevalent bacterial infections, affecting millions of people each year [1]. UTIs primarily affect women, and up to 50% of adult women have experienced at least one UTI episode during their lifetime. Recurrent UTIs are observed in a quarter of women within 6 months of initial diagnosis and in half of the women within one year of a UTI episode even after antimicrobial treatment [2]. Uropathogenic Escherichia coli (UPEC) remains, by far, the primary causative agent of uncomplicated UTIs [1]. Maintain, and to circumvent host defenses during an infection, UPEC are equipped with specialized virulence factors. Well-documented examples include adhesins (type 1, P, F1C, and S fimbriae), flagella, iron acquisition systems, a polysaccharide capsule and toxins such as hemolysin [3,4]

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