Differentiation of Crohn's Disease-Associated Isolates from Other Pathogenic Escherichia coli by Fimbrial Adhesion under Shear Force.

Sabine Szunerits,Dimitri Alvarez Dorta,Amaia Pesquera,Aritz Yanguas Serrano,Oleksandr Zagorodko,Thibaut Chalopin,Adeline Sivignon,Sébastien Gouin,Nicolas Barnich,Julie Bouckaert,Aloysius Siriwardena,Anne Harduin-Lepers,Amaia Zurutuza,Tetiana Dumych,Iban Larroulet,Virginie Cogez,Rabah Boukherroub

doi:10.3390/biology5020014

Abstract

Shear force exerted on uropathogenic Escherichia coli adhering to surfaces makes type-1 fimbriae stretch out like springs to catch on to mannosidic receptors. This mechanism is initiated by a disruption of the quaternary interactions between the lectin and the pilin of the two-domain FimH adhesin and transduces allosterically to the mannose-binding pocket of FimH to increase its affinity. Mannose-specific adhesion of 14 E. coli pathovars was measured under flow, using surface plasmon resonance detection on functionalized graphene-coated gold interfaces. Increasing the shear had important differential consequences on bacterial adhesion. Adherent-invasive E. coli, isolated from the feces and biopsies of Crohn’s disease patients, consistently changed their adhesion behavior less under shear and displayed lower SPR signals, compared to E. coli opportunistically infecting the urinary tract, intestines or loci of knee and hip prostheses. We exemplified this further with the extreme behaviors of the reference strains UTI89 and LF82. Whereas their FimA major pilins have identical sequences, FimH of LF82 E. coli is marked by the Thr158Pro mutation. Positioned in the inter-domain region known to carry hot spots of mutations in E. coli pathotypes, residue 158 is indicated to play a structural role in the allosteric regulation of type-1 fimbriae-mediated bacterial adhesion.

Highlights

The Gram-negative Escherichia coli (E. coli) species express type-1 pili or fimbriae, which are organelles integral to host receptor recognition and attachment [1]
We have shown that the adhesion of uropathogenic E. coli UTI89 can be conveniently studied by following the surface plasmon resonance (SPR) signals on the graphene-coated plasmonic interfaces [23,24]
Shear force enhancement has not been further investigated using E. coli isolates displaying a natural variation in FimH amino acids, which potentially plays a role in the allosteric regulation of receptor affinity for different E. coli pathotypes, until very recently [15]

Summary

Introduction

The Gram-negative Escherichia coli (E. coli) species express type-1 pili or fimbriae, which are organelles integral to host receptor recognition and attachment [1]. With an N-terminal mannose-binding lectin domain connected by a flexible linker to a pilin anchoring it to FimG and FimF in the tip fibrillum. Natural variations in amino acid composition were found to regulate the pathoadaptivity of E. coli [3], not frequently in or near the conserved mannose-binding pocket, but predominantly at the interface between the lectin and pilin domains of the FimH TDA. The structural basis for these observations remained obscure, until the crystal structure of the whole tip of E. coli type-1 fimbriae Electron microscopic analysis already pointed to the importance of the incorporation of FimH into E. coli type-1 fimbriae to the extensibility of the stubby and flexible tip fibrillum [2].

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Discussion

Conclusion