Structural and Functional Insight into the Carbohydrate Receptor Binding of F4 Fimbriae-producing Enterotoxigenic Escherichia coli

Moonens, Kristof; Broeck, Imke Van den; Kerpel, Maia De; Deboeck, Francine; Raymaekers, Hanne; Remaut, Han; Greve, Henri De

doi:10.1074/jbc.m114.618595

Cited by 29 publications

(23 citation statements)

References 59 publications

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“…Recent studies characterized some of the porcine intestinal carbohydrate receptor moieties interacting with the F4 fimbriae (162). Crystal structure comparisons of the FaeG variants and of the FaeG ad -lactose complex suggested different variant-specific binding pockets with a potential involvement of conformational changes for the adhesion process (163). Noticeably, all the intestinal ceramides that act as receptor for the F4, F5 and F6 fimbriae need to be hydroxylated (140, 162, 164, 165), indicating the importance of the lipid moiety in the binding properties of gangliosides with short carbohydrate chains.…”

Section: Adhesins and Host Receptorsmentioning

confidence: 99%

Animal EnterotoxigenicEscherichia coli

2016

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Enterotoxigenic Escherichia coli (ETEC) is the most common cause of E. coli diarrhea in farm animals. ETEC are characterized by the ability to produce two types of virulence factors; adhesins that promote binding to specific enterocyte receptors for intestinal colonization and enterotoxins responsible for fluid secretion. The best-characterized adhesins are expressed in the context of fimbriae, such as the F4 (also designated K88), F5 (K99), F6 (987P), F17 and F18 fimbriae. Once established in the animal small intestine, ETEC produces enterotoxin(s) that lead to diarrhea. The enterotoxins belong to two major classes; heat-labile toxin that consist of one active and five binding subunits (LT), and heat-stable toxins that are small polypeptides (STa, STb, and EAST1). This chapter describes the disease and pathogenesis of animal ETEC, the corresponding virulence genes and protein products of these bacteria, their regulation and targets in animal hosts, as well as mechanisms of action. Furthermore, vaccines, inhibitors, probiotics and the identification of potential new targets identified by genomics are presented in the context of animal ETEC.

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Section: Adhesins and Host Receptorsmentioning

confidence: 99%

Animal EnterotoxigenicEscherichia coli

2016

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“…Moreover, the size and structure of the galactose‐binding site resemble those in Myf and Psa (Supporting Information Fig. S11); for example, in the crystal structure of the FaeG‐lactose complex, the protein interacts with the galactose residue, which also lies flat on the surface of an aromatic side chain (Moonens et al ., ). Hence, it is not surprising that Y. enterocolitica , a strictly enteric pathogen, developed a similar carbohydrate binding specificity.…”

Section: Discussionmentioning

confidence: 97%

Structural basis for Myf and Psa fimbriae‐mediated tropism of pathogenic strains of Yersinia for host tissues

Pakharukova

Roy

Tuittila

et al. 2016

Molecular Microbiology

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Three pathogenic species of the genus Yersinia assemble adhesive fimbriae via the FGL-chaperone/usher pathway. Closely related Y. pestis and Y. pseudotuberculosis elaborate the pH6 antigen (Psa), which mediates bacterial attachment to alveolar cells of the lung. Y. enterocolitica, instead, assembles the homologous fimbriae Myf of unknown function. Here, we discovered that Myf, like Psa, specifically recognizes β1-3- or β1-4-linked galactose in glycosphingolipids, but completely lacks affinity for phosphatidylcholine, the main receptor for Psa in alveolar cells. The crystal structure of a subunit of Psa (PsaA) complexed with choline together with mutagenesis experiments revealed that PsaA has four phosphatidylcholine binding pockets that enable super-high-avidity binding of Psa-fibres to cell membranes. The pockets are arranged as six tyrosine residues, which are all missing in the MyfA subunit of Myf. Conversely, the crystal structure of the MyfA-galactose complex revealed that the galactose-binding site is more extended in MyfA, enabling tighter binding to lactosyl moieties. Our results suggest that during evolution, Psa has acquired a tyrosine-rich surface that enables it to bind to phosphatidylcholine and mediate adhesion of Y. pestis/pseudotuberculosis to alveolar cells, whereas Myf has specialized as a carbohydrate-binding adhesin, facilitating the attachment of Y. enterocolitica to intestinal cells.

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“…This hypothesis was confirmed by Moonens et al, they found that F4ad FaeG interacts via its D′‐D″‐α 1‐α 2 binding domain with the minimal galactose binding epitope, two short amino acid stretches Phe150–Glu152, and Val166–Glu170 are the key residues in the galactose–FaeG interaction. This crucial D′‐α 1 loop are lacking in the ab and ac variants and resulting in different structural and adhesive properties .…”

Section: Discussionmentioning

confidence: 99%

F4⁺enterotoxigenicEscherichia coli(ETEC) adhesion mediated by the major fimbrial subunit FaeG

Xia

Song

Zou

et al. 2015

J. Basic Microbiol.

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The FaeG subunit is the major constituent of F4(+) fimbriae, associated with glycoprotein and/or glycolipid receptor recognition and majorly contributes to the pathogen attachment to the host cells. To investigate the key factor involved in the fimbrial binding of F4(+) Escherichia coli, both the recombinant E. coli SE5000 strains carrying the fae operon gene clusters that express the different types of fimbriae in vitro, named as rF4ab, rF4ac, and rF4ad, respectively, corresponding to the fimbrial types F4ab, F4ac, and F4ad, and the three isogenic in-frame faeG gene deletion mutants were constructed. The adhesion assays and adhesion inhibition assays showed that ΔfaeG mutants had a significant reduction in the binding to porcine brush border as well as the intestinal epithelial cell lines, while the complemented strain ΔfaeG/pfaeG restored the adhesion function. The recombinant bacterial strains rF4ab, rF4ac, and rF4ad have the same binding property as wild-type F4(+) E. coli strains do and improvement in terms of binding to porcine brush border and the intestinal epithelial cells, and the adherence was blocked by the monoclonal antibody anti-F4 fimbriae. These data demonstrate that the fimbrial binding of F4(+) E. coli is directly mediated by the major FaeG subunit.

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Structural and Functional Insight into the Carbohydrate Receptor Binding of F4 Fimbriae-producing Enterotoxigenic Escherichia coli

Cited by 29 publications

References 59 publications

Animal EnterotoxigenicEscherichia coli

Animal EnterotoxigenicEscherichia coli

Structural basis for Myf and Psa fimbriae‐mediated tropism of pathogenic strains of Yersinia for host tissues

F4⁺enterotoxigenicEscherichia coli(ETEC) adhesion mediated by the major fimbrial subunit FaeG

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Structural and Functional Insight into the Carbohydrate Receptor Binding of F4 Fimbriae-producing Enterotoxigenic Escherichia coli

Cited by 29 publications

References 59 publications

Animal EnterotoxigenicEscherichia coli

Animal EnterotoxigenicEscherichia coli

Structural basis for Myf and Psa fimbriae‐mediated tropism of pathogenic strains of Yersinia for host tissues

F4+enterotoxigenicEscherichia coli(ETEC) adhesion mediated by the major fimbrial subunit FaeG

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F4⁺enterotoxigenicEscherichia coli(ETEC) adhesion mediated by the major fimbrial subunit FaeG