title: Signature-tagged mutagenesis and co-infection studies demonstrate the importance of P fimbriae in a murine model of urinary tract infection.
abstract: Escherichia coli is the leading cause of urinary tract infections (UTIs), one of the most common infections in humans. P fimbria was arguably the first proposed virulence factor for uropathogenic E. coli, based on the capacity of E. coli isolated from UTIs to adhere to exfoliated epithelial cells in higher numbers than fecal strains of E. coli. Overwhelming epidemiologic evidence has been presented for involvement of P fimbriae in colonization. It has been difficult, however, to demonstrate this requirement for uropathogenic strains in animal models of infections or in humans. In this study, a signature-tagged mutagenesis screen identified a P-fimbrial gene (papC) and 18 other genes as being among those required for full fitness of cystitis isolate E. coli F11. A P-fimbrial mutant was outcompeted by the wild-type strain in cochallenge in the murine model of ascending UTI, and this colonization defect could be complemented with the cloned pap operon. To our knowledge, this study is the first to fulfill molecular Koch's postulates in which a pathogenic strain was attenuated by mutation of pap genes and then complemented to restore fitness, confirming P fimbria as a virulence factor in a pathogenic clinical isolate.
authors: Division of Infectious Diseases, Department of Medicine, University of Maryland School of Medicine, HSF II, 20 Penn Street, Baltimore, MD 21201, USA.
authors: Eric L
authors: EL
authors: Buckles
authors: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors: Courtney L
authors: CL
authors: Luterbach
authors: Division of Infectious Diseases, Department of Medicine, University of Maryland School of Medicine, HSF II, 20 Penn Street, Baltimore, MD 21201, USA.
authors: Xiaolin
authors: X
authors: Wang
authors: Division of Infectious Diseases, Department of Medicine, University of Maryland School of Medicine, HSF II, 20 Penn Street, Baltimore, MD 21201, USA.
authors: C Virginia
authors: CV
authors: Lockatell
authors: Division of Infectious Diseases, Department of Medicine, University of Maryland School of Medicine, HSF II, 20 Penn Street, Baltimore, MD 21201, USA Department of Veterans Affairs, Baltimore, MD 21201, USA.
authors: David E
authors: DE
authors: Johnson
authors: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors: Harry L T
authors: HL
authors: Mobley
authors: Division of Infectious Diseases, Department of Medicine, University of Maryland School of Medicine, HSF II, 20 Penn Street, Baltimore, MD 21201, USA mdonnenb@umaryland.edu.
authors: Michael S
authors: MS
authors: Donnenberg
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001422:Bacterial Adhesion; D060085:Coinfection / Q000382:microbiology; D004195:Disease Models, Animal; D004927:Escherichia coli Infections / Q000382:microbiology*; D010861:Fimbriae, Bacterial / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D005816:Genetic Complementation Test; D005820:Genetic Testing; D051379:Mice; D016296:Mutagenesis; D009876:Operon; D014552:Urinary Tract Infections / Q000382:microbiology*; D056689:Uropathogenic Escherichia coli / Q000235:genetics / Q000502:physiology*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D018829:Adhesins, Bacterial; D037521:Virulence Factors
keywords: F11; UPEC; UTI; transposon mutagenesis; uropathogenic