title: Escherichia coli 83972 expressing a P fimbriae oligosaccharide receptor mimic impairs adhesion of uropathogenic E. coli.
abstract: Urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) are a significant health concern, exacerbated by the rapid emergence of multidrug resistant strains refractory to antibiotic treatment. P fimbriae are strongly associated with upper urinary tract colonization due to specific binding to α-D-galactopyranosyl-(1-4)-β-D-galactopyranoside receptors in the kidneys. Thus, inhibiting P-fimbrial adhesion may reduce the incidence of UPEC-mediated UTI. E. coli 83972 is an asymptomatic bacteriuria isolate successfully used as a prophylactic agent to prevent UTI in human studies. We constructed a recombinant E. coli 83972 strain displaying a surface-located oligosaccharide P fimbriae receptor mimic that bound to P-fimbriated E. coli producing any of the 3 PapG adhesin variants. The recombinant strain, E. coli 83972::lgtCE, impaired P fimbriae-mediated adhesion to human erythrocytes and kidney epithelial cells. Additionally, E. coli 83972::lgtCE impaired urine colonization by UPEC in a mouse UTI model, demonstrating its potential as a prophylactic agent to prevent UTI.
authors.affiliation: Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia.
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Watts
authors.forename: Chee K
authors.initials: CK
authors.lastname: Tan
authors.forename: Glen C
authors.initials: GC
authors.lastname: Ulett
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Carey
authors.forename: Makrina
authors.initials: M
authors.lastname: Totsika
authors.forename: Adi
authors.initials: A
authors.lastname: Idris
authors.forename: Adrienne W
authors.initials: AW
authors.lastname: Paton
authors.forename: Renato
authors.initials: R
authors.lastname: Morona
authors.forename: James C
authors.initials: JC
authors.lastname: Paton
authors.forename: Mark A
authors.initials: MA
authors.lastname: Schembri
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000382:microbiology; D004912:Erythrocytes / Q000382:microbiology; D005260:Female; D036781:Fimbriae Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009844:Oligosaccharides / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D014552:Urinary Tract Infections / Q000517:prevention & control; D056689:Uropathogenic Escherichia coli / Q000235:genetics / Q000472:pathogenicity*
chemical_list: D009844:Oligosaccharides; D036781:Fimbriae Proteins