Trivalent Cluster Mannosides with Aromatic Partial Structure as Ligands for the Type 1 Fimbrial Lectin of Escherichia coli

2002 ◽  
Vol 55 (2) ◽  
pp. 87 ◽  
Author(s):  
N. Röckendorf ◽  
O. Sperling ◽  
T. K. Lindhorst
Keyword(s):  
Bacterial Adhesion ◽  
Host Cells ◽  
Carbohydrate Binding ◽  
Partial Structure ◽  
E Coli ◽  
Type 1 Fimbriae ◽  
Chaperone Protein ◽  
Clustering Approach ◽  
Carbohydrate Binding Site

Mannose-specific adhesion of E. coli bacteria to their host cells is mediated by so-called type 1 fimbriae containing lectin domains present on the type 1 fimbrial FimH protein. The crystal structure of a FimH-FimC(chaperone) protein complex revealed a number of amino acids in the carbohydrate binding site with aromatic side chains. This finding is in keeping with earlier results showing high inhibitory potencies of aryl mannosides when tested as inhibitors of type 1 fimbriae-mediated bacterial adhesion. In addition, clustering of mannosyl moieties also led to favourable effects, as in the case of trivalent cluster mannosides such as (1). In order to combine both, i.e. the clustering approach and the advantage of an aromatic moiety, the herein presented study has emphasized the synthesis of three cluster mannosides (2), (3), and (4), as ligands for the type 1 fimbrial lectin, which contain a phenyl partial structure in different proximity to the core of the molecule. The inhibitory potencies of the new cluster mannosides were determined in enzyme-linked immunosorbent assays (ELISAs).

scholarly journals Are D-manno-configured Amadori products ligands of the bacterial lectin FimH?

2015 ◽  
Vol 11 ◽  
pp. 1096-1104 ◽  
Author(s):  
Tobias-Elias Gloe ◽  
Insa Stamer ◽  
Cornelia Hojnik ◽  
Tanja M Wrodnigg ◽  
Thisbe K Lindhorst
Keyword(s):  
Molecular Docking ◽  
Binding Site ◽  
Bacterial Adhesion ◽  
Carbohydrate Binding ◽  
Amadori Products ◽  
E Coli ◽  
Type D ◽  
Amadori Rearrangement ◽  
Carbohydrate Binding Site

The Amadori rearrangement was employed for the synthesis ofC-glycosyl-type D-mannoside analogues, namely 1-propargylamino- and 1-phenylamino-1-deoxy-α-D-manno-heptopyranose. They were investigated as ligands of type 1-fimbriatedE. colibacteria by means of molecular docking and bacterial adhesion studies. It turns out that Amadori rearrangement products have a limited activity as inhibitors of bacterial adhesion because the β-C-glycosidically linked aglycone considerably hampers complexation within the carbohydrate binding site of the type 1-fimbrial lectin FimH.

scholarly journals Functional Flexibility of the FimH Adhesin: Insights from a Random Mutant Library

2000 ◽  
Vol 68 (5) ◽  
pp. 2638-2646 ◽  
Author(s):  
Mark A. Schembri ◽  
Evgeni V. Sokurenko ◽  
Per Klemm
Keyword(s):  
Amino Acid ◽  
Conformational Changes ◽  
Binding Capacity ◽  
Random Mutagenesis ◽  
Yeast Cells ◽  
Carbohydrate Binding ◽  
Functional Changes ◽  
E Coli ◽  
Type 1 Fimbriae

ABSTRACT Type 1 fimbriae are surface organelles of Escherichia coli which mediate d-mannose-sensitive binding to different host surfaces. This binding is conferred by the minor fimbrial component FimH. Naturally occurring variants of the FimH protein have been selected in nature for their ability to recognize specific receptor targets. In particular, variants that bind strongly to terminally exposed monomannose residues have been associated with a pathogenicity-adaptive phenotype that enhances E. colicolonization of extraintestinal locations such as the urinary bladder. In this study we have used random mutagenesis to specifically identify nonselective mutations in the FimH adhesin which modify its binding phenotype. Isogenic E. coli clones expressing FimH variants were tested for their ability to bind yeast cells and model glycoproteins that contain oligosaccharide moieties rich in either terminal monomannose, oligomannose, or nonmannose residues. Both the monomannose- and the oligomannose-binding capacity of type 1 fimbriae could be altered by minor amino acid changes in the FimH protein. The monomannose-binding phenotype was particularly sensitive to changes, with extensive differences in binding being observed in comparison to wild-type FimH levels. Different structural alterations were able to cause similar functional changes in FimH, suggesting a high degree of flexibility to target recognition by this adhesin. Alteration of residue P49 of the mature FimH protein, which occurs within the recently elucidated carbohydrate-binding pocket of FimH, completely abolished its function. Amino acid changes that increased the binding capacity of FimH were located outside receptor-interacting residues, indicating that functional changes relevant to pathogenicity are likely to be due to conformational changes of the adhesin.

scholarly journals Synthesis and testing of the first azobenzene mannobioside as photoswitchable ligand for the bacterial lectin FimH

2013 ◽  
Vol 9 ◽  
pp. 223-233 ◽  
Author(s):  
Vijayanand Chandrasekaran ◽  
Katharina Kolbe ◽  
Femke Beiroth ◽  
Thisbe K Lindhorst
Keyword(s):  
Bacterial Adhesion ◽  
Water Solubility ◽  
Docking Studies ◽  
Solid Support ◽  
Photochromic Properties ◽  
Inhibitory Potency ◽  
E Coli ◽  
Type 1 Fimbriae ◽  
Computer Aided

In order to allow spatial and temporal control of carbohydrate-specific bacterial adhesion, it has become our goal to synthesise azobenzene mannosides as photoswitchable inhibitors of type 1 fimbriae-mediated adhesion of E. coli. An azobenzene mannobioside 2 was prepared and its photochromic properties were investigated. The E→Z isomerisation was found to be highly effective, yielding a long-lived (Z)-isomer. Both isomers, E and Z, show excellent water solubility and were tested as inhibitors of mannoside-specific bacterial adhesion in solution. Their inhibitory potency was found to be equal and almost two orders of magnitude higher than that of the standard inhibitor methyl mannoside. These findings could be rationalised on the basis of computer-aided docking studies. The properties of the new azobenzene mannobioside have qualified this glycoside to be eventually employed on solid support, in order to fabricate photoswitchable adhesive surfaces.

scholarly journals Type 1 fimbriae in commensal Escherichia coli derived from healthy humans.

2014 ◽  
Vol 61 (2) ◽  
Author(s):  
Paweł Pusz ◽  
Ewa Bok ◽  
Justyna Mazurek ◽  
Michał Stosik ◽  
Katarzyna Baldy-Chudzik
Keyword(s):  
Escherichia Coli ◽  
Gene Encoding ◽  
E Coli ◽  
Type 1 Fimbriae ◽  
Healthy Humans ◽  
Chaperone Protein ◽  
Genes Expression ◽  
Structural Subunit ◽  
Complete Set

Type 1 fimbriae are one of the most important factors of Escherichia coli adaptation to different niches in the host. Our study indicated that the genetic marker--fimH gene occurred commonly in commensal E. coli derived from healthy humans but expression of the type 1 fimbriae was not observed. Identification of fim structural subunit genes (fimA-fimH) and recombinase fimE and fimB genes showed that many of the strains were carrying an incomplete set of genes and the genes expression study revealed that in strains with complete set of fim genes, the fimC gene, encoding the chaperone protein, was not expressed.

scholarly journals Role of the ceramide-signaling pathway in cytokine responses to P-fimbriated Escherichia coli.

1996 ◽  
Vol 183 (3) ◽  
pp. 1037-1044 ◽  
Author(s):  
M Hedlund ◽  
M Svensson ◽  
A Nilsson ◽  
R D Duan ◽  
C Svanborg
Keyword(s):  
Escherichia Coli ◽  
Signaling Pathway ◽  
Kinase Inhibitors ◽  
Human Kidney ◽  
Cytokine Response ◽  
Protein Kinase Inhibitors ◽  
E Coli ◽  
Type 1 Fimbriae ◽  
Outer Leaflet

Escherichia coli express fimbriae-associated adhesins through which they attach to mucosal cells and activate a cytokine response. The receptors for E. coli P fimbriae are the globoseries of glycosphingolipids; Gal alpha 1-->4Gal beta-containing oligosaccharides bound to ceramide in the outer leaflet of the lipid bilayer. The receptors for type 1 fimbriae are mannosylated glycoproteins rather than glycolipids. This study tested the hypothesis that P-fimbriated E. coli elicit a cytokine response through the release of ceramide in the receptor-bearing cell. We used the A498 human kidney cell line, which expressed functional receptors for P and type 1 fimbriae and secreted higher levels of interleukin (IL)-6 when exposed to the fimbriated strains than to isogenic nonfimbriated controls. P-fimbriated E. coli caused the release of ceramide and increased the phosphorylation of ceramide to ceramide 1-phosphate. The IL-6 response to P-fimbriated E. coli was reduced by inhibitors of serine/threonine kinases but not by other protein kinase inhibitors. In contrast, ceramide levels were not influenced by type 1-fimbriated E. coli, and the IL-6 response was insensitive to the serine/threonine kinase inhibitors. These results demonstrate that the ceramide-signaling pathway is activated by P-fimbriated E. coli, and that the receptor specificity of the P fimbriae influences this process. We propose that this activation pathway contributes to the cytokine induction by P-fimbriated E. coli in epithelial cells.

scholarly journals Evolutionary Analysis Points to Divergent Physiological Roles of Type 1 Fimbriae in Salmonella and Escherichia coli

mBio ◽  
2013 ◽  
Vol 4 (2) ◽  
Author(s):  
Dagmara I. Kisiela ◽  
Sujay Chattopadhyay ◽  
Veronika Tchesnokova ◽  
Sandip Paul ◽  
Scott J. Weissman ◽  
...  
Keyword(s):  
Bacterial Species ◽  
Structural Diversity ◽  
Evolutionary Analysis ◽  
Content Type ◽  
E Coli ◽  
Type 1 Fimbriae ◽  
Gene Shuffling ◽  
Immune Pressure ◽  
High Level

ABSTRACTSalmonellaandEscherichia colimannose-binding type 1 fimbriae exhibit highly similar receptor specificities, morphologies, and mechanisms of assembly but are nonorthologous in nature, i.e., not closely related evolutionarily. Their operons differ in chromosomal location, gene arrangement, and regulatory components. In the current study, we performed a comparative genetic and structural analysis of the major structural subunit, FimA, fromSalmonellaandE. coliand found that FimA pilins undergo diverse evolutionary adaptation in the different species. Whereas theE. coli fimAlocus is characterized by high allelic diversity, frequent intragenic recombination, and horizontal movement,Salmonella fimAshows structural diversity that is more than 5-fold lower without strong evidence of gene shuffling or homologous recombination. In contrast toSalmonellaFimA, the amino acid substitutions in theE. colipilin heavily target the protein regions that are predicted to be exposed on the external surface of fimbriae. Altogether, our results suggest thatE. coli, but notSalmonella, type 1 fimbriae display a high level of structural diversity consistent with a strong selection for antigenic variation under immune pressure. Thus, type 1 fimbriae in these closely related bacterial species appear to function in distinctly different physiological environments.IMPORTANCEE. coliandSalmonellaare enteric bacteria that are closely related from an evolutionary perspective. They are both notorious human pathogens, though with somewhat distinct ecologies and virulence mechanisms. Type 1 fimbriae are rod-shaped surface appendages found in mostE. coliandSalmonellaisolates. In both species, they mediate bacterial adhesion to mannose receptors on host cells and share essentially the same morphology and assembly mechanisms. Here we show that despite the strong resemblances in function and structure, they are exposed to very different natural selection environments. Sequence analysis indicates thatE. coli, but notSalmonella, fimbriae are subjected to strong immune pressure, resulting in a high level of major fimbrial protein gene shuffling and interbacterial transfer. Thus, evolutionary analysis tools can provide evidence of divergent physiological roles of functionally similar traits in different bacterial species.

scholarly journals In Vivo Dynamics of Type 1 Fimbria Regulation in UropathogenicEscherichia coli during Experimental Urinary Tract Infection

2001 ◽  
Vol 69 (5) ◽  
pp. 2838-2846 ◽  
Author(s):  
Nereus W. Gunther ◽  
Virginia Lockatell ◽  
David E. Johnson ◽  
Harry L. T. Mobley
Keyword(s):  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Invertible Element ◽  
Molecular Techniques ◽  
E Coli ◽  
Type 1 Fimbriae ◽  
Invertible Elements

ABSTRACT Escherichia coli is the primary cause of uncomplicated infections of the urinary tract including cystitis. More serious infections, characterized as acute pyelonephritis, can also develop. Type 1 fimbriae of E. coli contribute to virulence in the urinary tract; however, only recently has the expression of the type 1 fimbriae been investigated in vivo using molecular techniques. Transcription of type 1 fimbrial genes is controlled by a promoter that resides on a 314-bp invertible element capable of two orientations. One places the promoter in the ON orientation, allowing for transcription; the other places the promoter in the OFF orientation, preventing transcription. A PCR-based assay was developed to measure the orientation of the invertible element during an experimental urinary tract infection in mice. Using this assay, it was found that the percentage of the population ON in urine samples correlated with the respective CFU per gram of bladder (P = 0.0006) but not with CFU per gram of kidney (P > 0.069). Cystitis isolates present in the urine of mice during the course of infection had a higher percentage of their invertible elements in the ON orientation than did pyelonephritis isolates (85 and 34%, respectively, at 24 h; P < 0.0001). In general, cystitis isolates, unlike pyelonephritis isolates, were more likely to maintain their invertible elements in the ON orientation for the entire period of infection. E. coli cells expressing type 1 fimbriae, expelled in urine, were shown by scanning electron microscopy to be densely packed on the surface of uroepithelial cells. These results suggest that expression of type 1 fimbriae is more critical for cystitis strains than for pyelonephritis strains in the early stages of an infection during bladder colonization.

scholarly journals Uropathogenic Escherichia coli Triggers Oxygen-Dependent Apoptosis in Human Neutrophils through the Cooperative Effect of Type 1 Fimbriae and Lipopolysaccharide

2004 ◽  
Vol 72 (8) ◽  
pp. 4570-4578 ◽  
Author(s):  
Robert Blomgran ◽  
Limin Zheng ◽  
Olle Stendahl
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract ◽  
Human Neutrophils ◽  
Dependent Manner ◽  
E Coli ◽  
Type 1 Fimbriae ◽  
The Difference ◽  
Tract Infections ◽  
Neutrophil Survival

ABSTRACT Type 1 fimbriae are the most commonly expressed virulence factor on uropathogenic Escherichia coli. In addition to promoting avid bacterial adherence to the uroepithelium and enabling colonization, type 1 fimbriae recruit neutrophils to the urinary tract as an early inflammatory response. Using clinical isolates of type 1 fimbriated E. coli and an isogenic type 1 fimbria-negative mutant (CN1016) lacking the FimH adhesin, we investigated if these strains could modulate apoptosis in human neutrophils. We found that E. coli expressing type 1 fimbriae interacted with neutrophils in a mannose- and lipopolysaccharide (LPS)-dependent manner, leading to apoptosis which was triggered by the intracellular generation of reactive oxygen species. This induced neutrophil apoptosis was abolished by blocking FimH-mediated attachment, by inhibiting NADPH oxidase activation, or by neutralizing LPS. In contrast, CN1016, which did not adhere to or activate the respiratory burst of neutrophils, delayed the spontaneous apoptosis in an LPS-dependent manner. This delayed apoptosis could be mimicked by adding purified LPS and was also observed by using fimbriated bacteria in the presence of d-mannose. These results suggest that LPS is required for E. coli to exert both pro- and antiapoptotic effects on neutrophils and that the difference in LPS presentation (i.e., with or without fimbriae) determines the outcome. The present study showed that there is a fine-tuned balance between type 1 fimbria-induced and LPS-mediated delay of apoptosis in human neutrophils, in which altered fimbrial expression on uropathogenic E. coli determines the neutrophil survival and the subsequent inflammation during urinary tract infections.

scholarly journals Adhesion of enteropathogenic, enterotoxigenic and commensal Escherichia coli to the Major Zymogen Granule Membrane Glycoprotein 2

2022 ◽  
Author(s):  
Christin Bartlitz ◽  
Rafał Kolenda ◽  
Jarosław Chilimoniuk ◽  
Krzysztof Grzymajło ◽  
Stefan Rödiger ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Host Specificity ◽  
Pathogenic Bacteria ◽  
Cell Receptor ◽  
Membrane Glycoprotein ◽  
Zymogen Granule ◽  
E Coli ◽  
Type 1 Fimbriae ◽  
Granule Membrane

Pathogenic bacteria, such as enteropathogenic (EPEC) and enterotoxigenic Escherichia coli (ETEC), cause diarrhea in mammals. In particular, E. coli colonize and infect the gastrointestinal tract via type 1 fimbriae (T1F). Here the major zymogen granule membrane glycoprotein 2 (GP2) acts as host cell receptor. GP2 is also secreted by the pancreas and various mucous glands, interacting with luminal type 1 fimbriae-positive E. coli . It is unknown whether GP2 isoforms demonstrate specific E. coli pathotype binding. In this study, we investigated interactions of human, porcine and bovine EPEC, ETEC as well as commensal E. coli isolates with human, porcine and bovine GP2. We first defined pathotype- and host-associated FimH variants. Secondly, we could prove that GP2 isoforms bound to FimH variants to varying degrees. However, the GP2-FimH interactions did not seem to be influenced by the host specificity of E. coli . In contrast, soluble GP2 affected ETEC infection and phagocytosis rates of macrophages. Pre-incubation of ETEC pathotype with GP2 reduced infection of cell lines. Furthermore, pre-incubation of E. coli with GP2 improved the phagocytosis rate of macrophages. Our findings suggest that GP2 plays a role in the defense against E. coli infection and in the corresponding host immune response. IMPORTANCE Infection by pathogenic bacteria such as certain Escherichia coli pathotypes results in diarrhea in mammals. Pathogens, including zoonotic agents, can infect different hosts or show host-specificity. There are Escherichia coli strains which are frequently transmitted between humans and animals, whereas other Escherichia coli strains tend to colonize only one host. This host-specificity is still not fully understood. We show that glycoprotein 2 is a selective receptor for particular Escherichia coli strains or variants of the adhesin FimH but not a selector for a species-specific Escherichia coli group. We demonstrate that GP2 is involved in the regulation of colonization and infection and thus represents a molecule of interest for the prevention or treatment of disease.

scholarly journals Selection for non-specific adhesion is a driver of FimH evolution increasing Escherichia coli biofilm capacity

2021 ◽  
Author(s):  
Mari YOSHIDA ◽  
Stanislas THIRIET-RUPERT ◽  
Leonie MAYER ◽  
Christophe BELOIN ◽  
Jean-Marc GHIGO
Keyword(s):  
Escherichia Coli ◽  
Selective Advantage ◽  
Coli Strain ◽  
Adhesion Properties ◽  
Lectin Domain ◽  
E Coli ◽  
Type 1 Fimbriae ◽  
Abiotic Surfaces ◽  
Selection For

Bacterial interactions with surfaces rely on the coordinated expression and interplay of surface exposed adhesion factors. However, how bacteria dynamically modulate their vast repertoire of adhesins to achieve surface colonization is not yet well-understood. We used experimental evolution and positive selection for improved adhesion to investigate how an initially poorly adherent Escherichia coli strain increased its adhesion capacities to abiotic surfaces. We showed that all identified evolved clones acquired mutations located almost exclusively in the lectin domain of fimH, the gene coding for the alpha-D-mannose-specific tip adhesin of type 1 fimbriae. While most of these fimH mutants showed reduced mannose-binding ability, they all displayed enhanced binding to abiotic surfaces, indicating a trade-off between FimH-mediated specific and non-specific adhesion properties. Several of the identified mutations were already reported in FimH lectin domain of pathogenic and environmental E. coli, suggesting that, beyond patho-adaptation, FimH microevolution favoring non-specific surface adhesion could constitute a selective advantage for natural E. coli isolates. Consistently, although E. coli deleted for the fim operon still evolves an increased adhesion capacity, mutants selected in the ∆fim background are outcompeted by fimH mutants revealing clonal interference for adhesion. Our study therefore provides insights into the plasticity of E. coli adhesion potential and shows that evolution of type 1 fimbriae is a major driver of the adaptation of natural E. coli to colonization.

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