title: Molecular characterization of UpaB and UpaC, two new autotransporter proteins of uropathogenic Escherichia coli CFT073.
abstract: Uropathogenic Escherichia coli (UPEC) is the primary cause of urinary tract infection (UTI) in the developed world. The major factors associated with virulence of UPEC are fimbrial adhesins, which mediate specific attachment to host receptors and trigger innate host responses. Another group of adhesins is represented by the autotransporter (AT) subgroup of proteins. The genome-sequenced prototype UPEC strain CFT073 contains 11 putative AT-encoding genes. In this study, we have performed a detailed molecular characterization of two closely related AT adhesins from CFT073: UpaB (c0426) and UpaC (c0478). PCR screening revealed that the upaB and upaC AT-encoding genes are common in E. coli. The upaB and upaC genes were cloned and characterized in a recombinant E. coli K-12 strain background. This revealed that they encode proteins located at the cell surface but possess different functional properties: UpaB mediates adherence to several ECM proteins, while UpaC expression is associated with increased biofilm formation. In CFT073, upaB is expressed while upaC is transcriptionally repressed by the global regulator H-NS. In competitive colonization experiments employing the mouse UTI model, CFT073 significantly outcompeted its upaB (but not upaC) isogenic mutant strain in the bladder. This attenuated phenotype was also observed in single-challenge experiments, where deletion of the upaB gene in CFT073 significantly reduced early colonization of the bladder.
authors.affiliation: Australian Infectious Disease Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, QLD, Australia.
authors.forename: Luke P
authors.initials: LP
authors.lastname: Allsopp
authors.forename: Christophe
authors.initials: C
authors.lastname: Beloin
authors.forename: Glen C
authors.initials: GC
authors.lastname: Ulett
authors.forename: Jaione
authors.initials: J
authors.lastname: Valle
authors.forename: Makrina
authors.initials: M
authors.lastname: Totsika
authors.forename: Orla
authors.initials: O
authors.lastname: Sherlock
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Ghigo
authors.forename: Mark A
authors.initials: MA
authors.lastname: Schembri
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D018441:Biofilms / Q000254:growth & development; D003001:Cloning, Molecular; D004269:DNA, Bacterial / Q000235:genetics; D004927:Escherichia coli Infections / Q000382:microbiology / Q000473:pathology; D048168:Escherichia coli K12 / Q000235:genetics / Q000472:pathogenicity; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D036781:Fimbriae Proteins / Q000378:metabolism; D020869:Gene Expression Profiling; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D014552:Urinary Tract Infections / Q000382:microbiology / Q000473:pathology; D056689:Uropathogenic Escherichia coli / Q000235:genetics* / Q000472:pathogenicity*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D018829:Adhesins, Bacterial; D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D016326:Extracellular Matrix Proteins; C529458:FimG protein, E coli; D026901:Membrane Transport Proteins; C569987:UpaB protein, E coli; C569988:UpaC protein, E coli; D037521:Virulence Factors; D036781:Fimbriae Proteins