BarA-UvrY Two-Component System Regulates Virulence of Uropathogenic E. coli CFT073

Senthilkumar Palaniyandi,Christopher D Herren,Xiaoping Zhu,Arindam Mitra,C Virginia Lockatell,Suman Mukhopadhyay,David E Johnson,Niyaz Ahmed

doi:10.1371/journal.pone.0031348

Abstract

Uropathogenic Escherichia coli (UPEC), a member of extraintestinal pathogenic E. coli, cause ∼80% of community-acquired urinary tract infections (UTI) in humans. UPEC initiates its colonization in epithelial cells lining the urinary tract with a complicated life cycle, replicating and persisting in intracellular and extracellular niches. Consequently, UPEC causes cystitis and more severe form of pyelonephritis. To further understand the virulence characteristics of UPEC, we investigated the roles of BarA-UvrY two-component system (TCS) in regulating UPEC virulence. Our results showed that mutation of BarA-UvrY TCS significantly decreased the virulence of UPEC CFT073, as assessed by mouse urinary tract infection, chicken embryo killing assay, and cytotoxicity assay on human kidney and uroepithelial cell lines. Furthermore, mutation of either barA or uvrY gene reduced the production of hemolysin, lipopolysaccharide (LPS), proinflammatory cytokines (TNF-α and IL-6) and chemokine (IL-8). The virulence phenotype was restored similar to that of wild-type by complementation of either barA or uvrY gene in trans. In addition, we discussed a possible link between the BarA-UvrY TCS and CsrA in positively and negatively controlling virulence in UPEC. Overall, this study provides the evidences for BarA-UvrY TCS regulates the virulence of UPEC CFT073 and may point to mechanisms by which virulence regulations are observed in different ways may control the long-term survival of UPEC in the urinary tract.

Highlights

In humans and animals, pathogenic E. coli causes both intestinal and extraintestinal infections [1]
urinary tract infection (UTI) is most often caused by ascending bacterial infection contaminating the periurethral area from the lower intestinal tract, colonizing the bladder via the urethra causing cystitis and in severe cases, further infecting the kidneys via the ureters resulting in pyelonephritis [6]
A hallmark of uropathogenic E. coli (UPEC) infection which is distinct from intestinal pathogenic E. coli is that UPEC has to invade the urinary tract for establishing infection

Summary

Introduction

Pathogenic E. coli causes both intestinal and extraintestinal infections [1]. Extraintestinal pathogenic E. coli (ExPEC), which includes uropathogenic E. coli (UPEC) and avian pathogenic E. coli, causes extraintestinal infections in different hosts [2]. Urinary tract infection (UTI) is considered to be the most common bacterial infection in humans [3]. UTI is most often caused by ascending bacterial infection contaminating the periurethral area from the lower intestinal tract, colonizing the bladder via the urethra causing cystitis and in severe cases, further infecting the kidneys via the ureters resulting in pyelonephritis [6]. A hallmark of UPEC infection which is distinct from intestinal pathogenic E. coli is that UPEC has to invade the urinary tract for establishing infection. UPEC isolates possess genes coding for various virulence factors like adhesins (eg. type 1, P fimbriae), iron acquisition system (eg. aerobactin, enterobactin), host immune evasion mechanisms (eg. capsule) and toxins (eg. cytotoxic necrotizing factor 1, hemolysin) [7,8]

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