The first step in the colonization of the human urinary tract by pathogenic Escherichia coli is the mannose-sensitive binding of FimH, the adhesin present at the tip of type 1 pili, to the bladder epithelium. We elucidated crystallographically the interactions of FimH with D-mannose. The unique site binding pocket occupied by D-mannose was probed using site-directed mutagenesis. All but one of ...

Using the combination method with PCR phylogrouping and fimH SNPs analysis, this study investigates the epidemiology of Extra-intestinal pathogenic E. coli in China. 116 E. coli strains including (74 from Urine, 39 from other extra-intestinal sources and 3 references strains) were collected. The bacteria Genomic DNA were extracted; phylogroup and the fimH gene amplifications were determined by ...

Salmonella enterica serovar Typhimurium can be internalized by immature dendritic cells (DCs). The interacting host and bacterial molecules initiating this process remain uncharacterized. The objective of this study was to investigate whether specific fimbriae are involved in the early step of binding and uptake of Salmonella by DCs. Type 1 fimbriated S. enterica serovar Typhimurium or recombin...

In an effort to better understand genetic and cellular factors that influence innate immunity, we examined host and bacterial factors involved in the nonopsonic phagocytosis and killing of Escherichia coli K-12 by mouse macrophages. Unelicited (resident) peritoneal macrophages from five different mouse strains, BALB/c, C57BL/6, CD-1, C3H/HeJ, and C3H/HeN, were employed. Additional macrophage po...

Adhesion of pathogen to host cells is an important prerequisite for successful colonization and establishment of the pathogenesis. The aim of this study is to examine the function of FimH adhesin in the adherence of avian pathogenic E. coli to porcine intestinal epithelial cell lines (IPEC-J2) and human lung epithelial cell line (A549) in an in vitro infection model. Three strains of avian path...

Naturally occurring adhesins bind to specific molecular targets in a lock-and-key fashion due to the composition of the binding domain of the adhesin. By introduction of random peptide libraries in a suitable surface exposed carrier protein it is possible to create and select designer adhesins with novel binding affinities. Type 1 fimbriae are surface organelles of Escherichia coli which mediat...

Enterotoxigenic Escherichia coli (ETEC), defined by their elaboration of heat-labile (LT) and/or heat-stable (ST) enterotoxins, are a common cause of diarrheal illness in developing countries. Efficient delivery of these toxins requires ETEC to engage target host enterocytes. This engagement is accomplished using a variety of pathovar-specific and conserved E. coli adhesin molecules as well as ...

Correlations between FimH mutations and virulence were established by studying a collection of human commensal and extraintestinal pathogenic Escherichia coli natural isolates. Pathoadaptive (A27V and, to a lesser extent, A119V) and "commensal-adaptive" (A202V) mutations were evidenced in B2 phylogenetic group strains. fimH phylogenetic analysis indicates that these pathoadaptive mutations occu...

A peptide library targeting protein-protein interactions crucial for pilus assembly in Gram negative bacteria has been designed using statistical molecular design. A nonamer peptide scaffold was used, with seven positions being varied. The selection was performed in the building block space, and previously known structure-activity data were included in the design procedure. This resulted in a h...

Antagonists of the Escherichia coli type-1 fimbrial adhesin FimH are recognized as attractive alternatives for antibiotic therapies and prophylaxes against acute and recurrent bacterial infections. In this study α-d-mannopyranosides O- or C-linked with an alkyl, alkene, alkyne, thioalkyl, amide, or sulfonamide were investigated to fit a hydrophobic substituent with up to two aryl groups within ...