title: CD46 (membrane cofactor protein) acts as a human epithelial cell receptor for internalization of opsonized uropathogenic Escherichia coli.
abstract: Escherichia coli is a common urinary pathogen whose uptake into epithelial cells is mediated by attachment through type 1 fimbriae. In this study, we show by using using human urinary tract epithelial cells that maximal internalization of E. coli is achieved only when bacteria are opsonized with complement. The concentrations of complement proteins in the urine rise sufficiently during infection to allow bacterial opsonization. The complement regulatory protein, CD46 (membrane cofactor protein), acts in cohort with fimbrial adhesion to promote the uptake of pathogenic E. coli. This uptake is inhibited by RNA interference to lower the expression of CD46 and by soluble CD46 that will competitively inhibit opsonized bacteria binding to cell surface CD46. We propose that efficient internalization of uropathogenic E. coli by the human urinary tract depends on cooperation between fimbrial-mediated adhesion and C3 receptor (CD46)-ligand interaction. Complement receptor-ligand interaction could pose a new target for interrupting the cycle of reinfection due to intracellular bacteria.
authors.affiliation: Department of Nephrology and Transplantation, Guy's Hospital, King's College London, United Kingdom.
authors.forename: Ke
authors.initials: K
authors.lastname: Li
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Feito
authors.forename: Steven H
authors.initials: SH
authors.lastname: Sacks
authors.forename: Neil S
authors.initials: NS
authors.lastname: Sheerin
mesh_terms: D000907:Antibodies, Bacterial / Q000378:metabolism; D001422:Bacterial Adhesion / Q000276:immunology; D002460:Cell Line; D003176:Complement C3 / Q000652:urine; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D004926:Escherichia coli / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000276:immunology* / Q000382:microbiology; D010861:Fimbriae, Bacterial / Q000276:immunology; D006801:Humans; D051916:Membrane Cofactor Protein / Q000502:physiology*; D009895:Opsonin Proteins / Q000378:metabolism*; D010587:Phagocytosis / Q000276:immunology*; D014552:Urinary Tract Infections / Q000276:immunology* / Q000382:microbiology
chemical_list: D000907:Antibodies, Bacterial; C497857:CD46 protein, human; D003176:Complement C3; D051916:Membrane Cofactor Protein; D009895:Opsonin Proteins