Structure of CFA/I fimbriae from enterotoxigenic
            <i>Escherichia coli</i>

Li, Yongfu; Poole, S.; Nishio, Kazuya; Jang, Ken; Rasulova, Fatima; McVeigh, Annette L.; Savarino, Stephen J.; Xia, Di; Bullitt, Esther

doi:10.1073/pnas.0812843106

Cited by 86 publications

(120 citation statements)

References 33 publications

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“…The overall structure of EcpA is quite similar to the Ig-like fold of other CU pilins (23,24), and the Dali server (27) identified the major colonization factor antigen I (CFA/I) pilin CfaB [Protein Data Bank (PDB) ID code 3f84 (28)] as having high tertiary homology (Z score: 12.3; rmsd: 3.1 Ǻ ; Fig. S6); however, EcpA is much larger, with dimensions ∼25 × 25 × 60 Ǻ, and is composed of ∼50% hydrophobic residues.…”

Section: Discussionmentioning

confidence: 99%

Structural insights into the biogenesis and biofilm formation by the Escherichia coli common pilus

Garnett

Martínez-Santos

Saldaña

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Bacteria have evolved a variety of mechanisms for developing community-based biofilms. These bacterial aggregates are of clinical importance, as they are a major source of recurrent disease. Bacterial surface fibers (pili) permit adherence to biotic and abiotic substrates, often in a highly specific manner. The Escherichia coli common pilus (ECP) represents a remarkable family of extracellular fibers that are associated with both disease-causing and commensal strains. ECP plays a dual role in early-stage biofilm development and host cell recognition. Despite being the most common fimbrial structure, relatively little is known regarding its biogenesis, architecture, and function. Here we report atomic-resolution insight into the biogenesis and architecture of ECP. We also derive a structural model for entwined ECP fibers that not only illuminates interbacteria communication during biofilm formation but also provides a useful foundation for the design of novel nanofibers.chaperone-usher | donor-strand exchange | X-ray crystallography T he long coexistence between bacteria and their eukaryote hosts has fine-tuned their relationships. These microorganisms have developed remarkable molecular systems for the trafficking of molecules across the cell envelope and exchanging signals with their environment. Historically, bacteria have been studied during their planktonic life cycle, although a matrix-enclosed, organized-community lifestyle is a frequent mode of growth for countless species that exist in diverse environments. Many bacteria produce surface fibers allowing them to adhere to each other and to biotic and abiotic surfaces (1, 2). Furthermore, many of these fibers are able to recognize specific host cell receptors during the first steps of host colonization and subsequent biofilm formation (3). These bacterial aggregates are of clinical importance, as they are a major source of recurrent disease allowing reservoirs of bacteria to persist in a host or the environment. Biofilms also contribute to increased resistance to antibiotics, the immune system, and host clearance mechanisms (4).Escherichia coli are primarily commensal colonizers of the human and other animal bowels, contributing to a healthy host immune system. Conversely, there are a number of virulent strains that are important causative agents of many diarrheal diseases such as hemorrhagic colitis (4). Upon entering extraintestinal sites, pathogenic strains can also lead to neonatal meningitis, urinary tract infections, sepsis, and pneumonia (5). The effects of such gastrointestinal and urinary tract diseases in the developing world are considerable (6), and they are estimated to kill around 2.5 million people every year, mostly young children (7).The E. coli common pilus (ECP), encoded by the ecpRABCDE operon, is an extracellular adhesive fiber first documented in association with E. coli strains causing newborn meningitis and septicaemia (NMEC), where it was originally named the Mat (meningitis-associated and temperature-regulated) fimbriae (8). Furthe...

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Section: Discussionmentioning

confidence: 99%

Structural insights into the biogenesis and biofilm formation by the Escherichia coli common pilus

Garnett

Martínez-Santos

Saldaña

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…Our results provide evidence that CS6 is a hydrophilic, spherical and hetero-oligomeric CF, contrary to other CFs like CFA/I, CFA/III, CS4 and CS5, which are described as elongated rod like structures (Knutton et al, 1989;Lüdi et al, 2006;Li et al, 2009). However, further investigation is required to examine whether the extent of CS6 oligomerization favours its colonization ability and ETEC pathogenesis.…”

Section: Discussionmentioning

confidence: 70%

Characterization of oligomeric assembly of colonization factor CS6 from enterotoxigenic Escherichia coli

et al. 2016

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The widely distributed colonization factor (CF) CS6 of enterotoxigenic Escherichia coli (ETEC) has gained importance over the years in terms of its structure and function. CS6 is an afimbrial assembly in contrast to the other ETEC CFs, which are mostly fimbrial. A recent study predicted a linear fibre model for recombinant chimeric CS6 and formation of oligomers in solution. In this study, we characterized the oligomeric assembly of CS6, purified from a clinical ETEC isolate and identified its existence in the WT strain. We found that purified CS6 forms a continuous array of higher order oligomers composed of two tightly associated subunits, CssA and CssB in an equal (1:1) stoichiometry. This oligomerization occurs by formation of (CssA-CssB) n complex where 'n' increases with the concentration. The diameter of CS6 oligomers also proportionally increases with concentration. More significantly, we showed CS6 oligomers to be spherical in shape instead of being linear fibres as predicted earlier and this was further confirmed by electron microscopy. We also showed CS6 assembled on the bacterial surface in the form of an oligomeric complex. This process depends on the expression of properly folded CssA and CssB together, guided by the chaperone CssC and usher CssD. In conclusion, our results provide evidence for the existence of concentration-dependent, spherical oligomers of CS6 comprising both the structural subunits in equal stoichiometry and the CS6 oligomeric complex on the ETEC surface.

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“…3C). Unlike rod-shaped fimbriae such as CFA/I, where the connection between the two major subunits CfaB is a single proline residue (30), the intersubunit connection for a Psa fimbria has four residues (48-KGQL-51) that makes it very flexible and allows simultaneous binding by a number of subunits to available receptors, as previously described with polymeric inhibitors (5). Additive fimbrial binding to the two cell receptors (5) suggested simultaneous binding to both receptors, consistent with the subunit crystal structure with its two receptors.…”

Section: Discussionmentioning

confidence: 99%

Structural basis for the specific recognition of dual receptors by the homopolymeric pH 6 antigen (Psa) fimbriae of Yersinia pestis

Bao

Nair

Tang

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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The pH 6 antigen (Psa) of Yersinia pestis consists of fimbriae that bind to two receptors: β1-linked galactosyl residues in glycosphingolipids and the phosphocholine group in phospholipids. Despite the ubiquitous presence of either moiety on the surface of many mammalian cells, Y. pestis appears to prefer interacting with certain types of human cells, such as macrophages and alveolar epithelial cells of the lung. The molecular mechanism of this apparent selectivity is not clear. Site-directed mutagenesis of the consensus choline-binding motif in the sequence of PsaA, the subunit of the Psa fimbrial homopolymer, identified residues that abolish galactosylceramide binding, phosphatidylcholine binding, or both. The crystal structure of PsaA in complex with both galactose and phosphocholine reveals separate receptor binding sites that share a common structural motif, thus suggesting a potential interaction between the two sites. Mutagenesis of this shared structural motif identified Tyr126, which is part of the choline-binding consensus sequence but is found in direct contact with the galactose in the structure of PsaA, important for both receptor binding. Thus, this structure depicts a fimbrial subunit that forms a polymeric adhesin with a unique arrangement of dual receptor binding sites. These findings move the field forward by providing insights into unique types of multiple receptor-ligand interactions and should steer research into the synthesis of dual receptor inhibitor molecules to slow down the rapid progression of plague.adhesin-receptor complex | adhesion | ligand binding | sugar binding | phosphocholine binding

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Structure of CFA/I fimbriae from enterotoxigenic Escherichia coli

Cited by 86 publications

References 33 publications

Structural insights into the biogenesis and biofilm formation by the Escherichia coli common pilus

Structural insights into the biogenesis and biofilm formation by the Escherichia coli common pilus

Characterization of oligomeric assembly of colonization factor CS6 from enterotoxigenic Escherichia coli

Structural basis for the specific recognition of dual receptors by the homopolymeric pH 6 antigen (Psa) fimbriae of Yersinia pestis

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