title: BarA-UvrY two-component system regulates virulence of uropathogenic E. coli CFT073.
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.
authors.affiliation: Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, United States of America.
authors.forename: Senthilkumar
authors.initials: S
authors.lastname: Palaniyandi
authors.forename: Arindam
authors.initials: A
authors.lastname: Mitra
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Herren
authors.forename: C Virginia
authors.initials: CV
authors.lastname: Lockatell
authors.forename: David E
authors.initials: DE
authors.lastname: Johnson
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhu
authors.forename: Suman
authors.initials: S
authors.lastname: Mukhopadhyay
mesh_terms: D000818:Animals; D001681:Biological Assay; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002642:Chick Embryo; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D006460:Hemolysin Proteins / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009154:Mutation / Q000235:genetics; D010770:Phosphotransferases / Q000235:genetics / Q000378:metabolism*; D012756:Sheep; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014552:Urinary Tract Infections / Q000382:microbiology / Q000473:pathology; D056689:Uropathogenic Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity*; D014774:Virulence / Q000187:drug effects
chemical_list: D016207:Cytokines; D029968:Escherichia coli Proteins; D006460:Hemolysin Proteins; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D014157:Transcription Factors; C419603:UvrY protein, E coli; C074276:barA protein, E coli; D010770:Phosphotransferases