Disease relevance of ECs5273

• In contrast to the antigenic heterogeneity of the major FimA subunit, the antigenic structure of FimH is conserved among different strains of E. coli [1].
• Type 1 fimbriae of enterobacteria are heteropolymeric organelles of adhesion composed of FimH, a mannose-binding lectin, and a shaft composed primarily of FimA [2].
• Characterization of Shigella type 1 fimbriae: expression, FimA sequence, and phase variation [3].
• The amino acid sequence of EfaA shows 55 to 60% homology to a group of streptococcal proteins, FimA from Streptococcus parasanguis, SsaB from Streptococcus sanguis, ScaA from Streptococcus gordonii, and PsaA from Streptococcus pneumoniae [4].
• This periodontal pathogen also expresses a polypeptide homologous to the 31-kDa Haemophilus influenzae protein, which shows amino acid sequence homology with the FimA and YfeA proteins from Streptococcus parasanguis and Yersinia pestis, respectively [5].

High impact information on ECs5273

• Until recently, it was thought that the D-mannose binding site was located in the major structural subunit (FimA), of relative molecular mass (Mr) 17,000 (17 K), of these organelles in Escherichia coli [1].
• Furthermore, beads coated with FimH but not with FimA, the major subunit of type 1 fimbriae, evoked mast cell release of histamine in vivo in amounts comparable to that elicited by type 1 fimbriated E. coli [6].
• Type 1 fimbriae of Escherichia coli mediate mannose-specific adhesion to host epithelial surfaces and consist of a major, antigenically variable pilin subunit, FimA, and a minor, structurally conserved adhesive subunit, FimH, located on the fimbrial tip [7].
• However, no further significant FimA diversification has occurred via point mutation after the transfers [7].
• The amino acid sequence of S. flexneri type 1 FimA contained 18 substitutions compared to that of Escherichia coli fimbrillin [3].

Chemical compound and disease context of ECs5273

• Essentially the same result was observed when the type 1-piliated E. coli K-12 strain ORN152 was fed to streptomycin-treated mice together with a nearly isogenic K-12 FimA- strain, ORN151 [8].
• The effect of glucose could be partially reversed by growing E. coli F-18 FimA- in nutrient broth containing 1% D-glucose supplemented with cyclic AMP (greater than or equal to 1 mM) [9].

Biological context of ECs5273

• This study elucidated the molecular structure and the degree of conservation of FimH and FimA among various avian pathogenic E. coli strains [10].

Anatomical context of ECs5273

• These results suggest that glucose-induced settling is, at least in part, regulated in a way related to catabolite repression and that the ability of E. coli F-18 FimA- to form microcolonies plays an important role in its ability to colonize streptomycin-treated mouse large intestine [9].

Analytical, diagnostic and therapeutic context of ECs5273

• Immunoelectron microscopy revealed FimA was localized at the tips of the fimbriae of FW213 [11].
• Sera raised against fimbriae from two of the clones (HB101/pPKL5 and HB101/pPKL4) were found by immunoblotting to be specific respectively for the major structural protein only (FimA), and for all components [12].
• The sequence analysis demonstrated that FimH is highly conserved among all investigated APEC strains (>99% homology), whereas the major subunit FimA is less conserved, presenting 6 variable regions distributed along the protein [10].

References