Identification of factors in human urine that inhibit the binding of Escherichia coli adhesins. Infect Immun 56: 2623 (original) (raw)
Related papers
Binding characteristics of Escherichia coli adhesins in human urinary bladder
Infection and Immunity
We studied domains in the human bladder that acted as receptors for Escherichia coli P, S, type 1, type 1C, and O75X fimbriae or adhesin and domains in the human kidneys that were receptors for E. coli type 1C fimbriae. Binding sites in frozen tissue sections were localized by direct staining with fluorochrome-labeled recombinant strains and by indirect immunofluorescence with the purified adhesins. In the bladder, the P and S fimbriae showed closely similar binding to the epithelial and muscular layers, and the S fimbriae also bound to the connective tissue elements. Type 1 fimbriae bound to vascular walls and to muscle cells, whereas the O75X adhesin bound avidly to connective tissue elements and to some extent to epithelial and muscle cells of the bladder. The type 1C fimbriae bound to distal tubules and collecting ducts of the kidney and to vascular endothelial cells in both the kidney and bladder. The binding of all adhesin types was inhibited by specific receptor analogs or Fa...
Characterisation of Escherichia coli adhesins in patients with symptomatic urinary tract infections
Sexually Transmitted Infections, 1989
The ability of bacteria to adhere to the epithelial cells of hosts has been shown to be mediated by adhesins. Many of these show readily demonstrable haemagglutinating activity. Of 109 Escherichia coli strains isolated from patients with symptomatic urinary tract infection, 11 (10. 1 %) were identified by their haemagglutinating properties as being P fimbriated, which was confirmed by the latex bead test. Other classes of adhesins, termed X and "other", were found in mannose resistant haemagglutinating E coli strains, which represented 4.6% (5) and 0 9% (1), respectively, of all the strains.
Influence of adhesins on the interaction of Escherichia coli with human phagocytes
Infection and Immunity
The fitness between bacterial adhesins and target cell receptors, determining bacterial adherence to epithelial cells in urinary tract infections, was shown to influence also the interaction with human polymorphonuclear leukocytes (PMNL). Two sets of homogenic strains, constructed to express either, both, or none of the globotetraosylceramide-sensitive (GS) adhesins specific for globoseries glycolipid receptors or the mannose-sensitive (MS) adhesins inhibited by alpha-methyl mannoside were compared regarding charge, hydrophobicity, and binding to PMNL. The mutants of a hydrophilic pyelonephritis strain required MS adhesins for binding to and activation of the PMNL. Removal of the MS adhesins from the mutant carrying both MS and GS adhesins abolished chemiluminescence and binding. A pronounced chemiluminescence reaction was induced by the hydrophobic strain without GS or MS adhesins . Transformants of this strain expressing the MS adhesin bound to and activated the PMNL. Poor binding...
Molecular …, 2006
Mannose-binding type 1 pili are important virulence factors for the establishment of Escherichia coli urinary tract infections (UTIs). These infections are initiated by adhesion of uropathogenic E. coli to uroplakin receptors in the uroepithelium via the FimH adhesin located at the tips of type 1 pili. Blocking of bacterial adhesion is able to prevent infection. Here, we provide for the first time binding data of the molecular events underlying type 1 fimbrial adherence, by crystallographic analyses of the FimH receptor binding domains from a uropathogenic and a K-12 strain, and affinity measurements with mannose, common monoand disaccharides, and a series of alkyl and aryl mannosides. Our results illustrate that the lectin domain of the FimH adhesin is a stable and functional entity and that an exogenous butyl a a a a -D -mannoside, bound in the crystal structures, exhibits a significantly better affinity for FimH (K d = 0.15 m m m m M) than mannose (K d = 2.3 m m m m M). Exploration of the binding affinities of a a a a -D -mannosides with longer alkyl tails revealed affinities up to 5 nM. Aryl mannosides and fructose can also bind with high affinities to the FimH lectin domain, with a 100-fold improvement and 15-fold reduction in affinity, respectively, compared with mannose. Taken together, these relative FimH affinities correlate exceptionally well with the relative concentrations of the same glycans needed for the inhibition of adherence of type 1 piliated E. coli . We foresee that our findings will spark new ideas and initiatives for the development of UTI vaccines and anti-adhesive drugs to prevent anticipated and recurrent UTIs.
Proceedings of the National Academy of Sciences, 1994
Nonobstructive acute pyelonephritis in humans is most often caused by P-fimbriated Escherichia coli. P-fimbriae are heteropolymeric fibers carrying a Gal(alpha 1-4)Gal-specific PapG adhesin at its distal end. The pyelonephritic strain DS17 expresses P-fimbriae from a single gene cluster. A mutant strain, DS17-8, which expresses P-fimbriae tacking the PapG adhesin, was constructed by allelic replacement introducing a 1-bp deletion early in the papG gene. In cynomolgus monkeys, DS17 and DS17-8 were equally able to cause bladder infection, whereas only the wild-type strain DS17 could cause pyelonephritis as monitored by bacteriological, functional, and histopathological criteria. Since DS17, but not DS17-8, adheres to renal tissue, these data underscore the critical role of microbial adherence to host tissues in infectious disease and strongly suggest that the PapG tip adhesin of P-fimbriae is essential in the pathogenesis of human kidney infection.
Microbial Pathogenesis, 1986
Hoekstra and H. Bergmans. The role of fimbriae of uropathogenic Escherichia coli as carriers of the adhesin involved in mannose-resistant hemagglutination. Microbial Pathogenesis 1986 ; 1 : 51-56. The gene clusters encoding various P-fimbriae (F7 1 , F7 2, F9 and F11) were compared. Deletion plasmids that lack the gene encoding the fimbrillin were derived from these gene clusters. Introduction of these deletion plasmids into an E. coli K1 2 strain resulted in non-fimbriated cells that still showed mannose-resistant hemagglutination (MRHA). However when introduced into wild type E. coli strains no MRHA was observed. Derivatives of the wild type E, coli strains with reduced amounts of 0-antigen on the other hand showed MRHA when harbouring these plasmids. These results indicate that adhesion and presence of fimbriae are not necessarily linked. P-fimbriae could function as a carrier for the adhesin and thus endow adhesive capacity to cells with a complete O-antigen .
The Journal of experimental medicine, 1995
Human urinary tract infection is an infectious disease that depends on a series of host-microbial interactions. The bacteria first colonize the colon and then the periurethral/vaginal areas; they ascend to and infect first the bladder and then the kidneys. Expression of Escherichia coli P-fimbriae constitutes the strongest correlation to renal pathogenicity, but is also related to first-time cystitis in children. The role of P-fimbriae in the preceding steps in the infectious process is unknown. To examine this, we constructed, from a P-fimbriated E. coli strain with a class II G-adhesin preferentially binding to globoside, one isogenic mutant lacking the G-adhesin and another isogenic mutant in which we replaced the papG class II allele with a class III adhesin preferentially binding to the Forssman antigen. We report here the comparison of the adhesin knockout mutant (DS17-8) and the class-switch mutant (DS17-1) with the wild-type (DS17) for in vivo colonization of the gut, vagina...
Journal of Urology, 2006
Mannose-binding type 1 pili are important virulence factors for the establishment of Escherichia coli urinary tract infections (UTIs). These infections are initiated by adhesion of uropathogenic E. coli to uroplakin receptors in the uroepithelium via the FimH adhesin located at the tips of type 1 pili. Blocking of bacterial adhesion is able to prevent infection. Here, we provide for the first time binding data of the molecular events underlying type 1 fimbrial adherence, by crystallographic analyses of the FimH receptor binding domains from a uropathogenic and a K-12 strain, and affinity measurements with mannose, common monoand disaccharides, and a series of alkyl and aryl mannosides. Our results illustrate that the lectin domain of the FimH adhesin is a stable and functional entity and that an exogenous butyl a a a a -D -mannoside, bound in the crystal structures, exhibits a significantly better affinity for FimH (K d = 0.15 m m m m M) than mannose (K d = 2.3 m m m m M). Exploration of the binding affinities of a a a a -D -mannosides with longer alkyl tails revealed affinities up to 5 nM. Aryl mannosides and fructose can also bind with high affinities to the FimH lectin domain, with a 100-fold improvement and 15-fold reduction in affinity, respectively, compared with mannose. Taken together, these relative FimH affinities correlate exceptionally well with the relative concentrations of the same glycans needed for the inhibition of adherence of type 1 piliated E. coli . We foresee that our findings will spark new ideas and initiatives for the development of UTI vaccines and anti-adhesive drugs to prevent anticipated and recurrent UTIs.