title: Molecular variations in Klebsiella pneumoniae and Escherichia coli FimH affect function and pathogenesis in the urinary tract.
abstract: Type 1 pili mediate binding, invasion, and biofilm formation of uropathogenic Escherichia coli (UPEC) in the host urothelium during urinary tract infection (UTI) via the adhesin FimH. In this study, we characterized the molecular basis of functional differences between FimH of the UPEC isolate UTI89 and the Klebsiella pneumoniae cystitis isolate TOP52. Type 1 pili characteristically mediate mannose-sensitive hemagglutination of guinea pig erythrocytes. Although the adhesin domain of K. pneumoniae TOP52 FimH (FimH(52)) is highly homologous to that of E. coli, with an identical mannose binding pocket and surrounding hydrophobic ridge, it lacks the ability to agglutinate guinea pig erythrocytes. In addition, FimH-dependent biofilm formation in K. pneumoniae is inhibited by heptyl mannose, but not methyl mannose, suggesting the need for contacts outside of the mannose binding pocket. The binding specificity differences observed for FimH(52) resulted in significant functional differences seen in the pathogenesis of K. pneumoniae UTI compared to E. coli UTI. Infections in a murine model of UTI demonstrated that although the K. pneumoniae strain TOP52 required FimH(52) for invasion and IBC formation in the bladder, FimH(52) was not essential for early colonization. This work reveals that a limited amount of sequence variation between the FimH of E. coli and K. pneumoniae results in significant differences in function and ability to colonize the urinary tract.
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Rosen
authors.forename: Jerome S
authors.initials: JS
authors.lastname: Pinkner
authors.forename: Jennifer N
authors.initials: JN
authors.lastname: Walker
authors.forename: Jennifer Stine
authors.initials: JS
authors.lastname: Elam
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Jones
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Hultgren
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D018830:Adhesins, Escherichia coli / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D004926:Escherichia coli / Q000145:classification / Q000235:genetics / Q000472:pathogenicity*; D005260:Female; D036781:Fimbriae Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014644:Genetic Variation; D006168:Guinea Pigs; D054884:Host-Pathogen Interactions; D007711:Klebsiella pneumoniae / Q000145:classification / Q000235:genetics / Q000472:pathogenicity*; D051379:Mice; D008809:Mice, Inbred C3H; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA; D014551:Urinary Tract / Q000382:microbiology; D014552:Urinary Tract Infections / Q000382:microbiology
chemical_list: D018829:Adhesins, Bacterial; D018830:Adhesins, Escherichia coli; C058769:fimH protein, E coli; D036781:Fimbriae Proteins