Oligomannoside-type glycopeptides inhibiting adhesion of Escherichia coli strains mediated by type 1 pili: preparation of potent inhibitors from plant glycoproteins.

Various structurally defined glycopeptides of natural origin were tested as inhibitors of guinea pig erythrocyte agglutination by enteropathogenic Escherichia coli strains expressing type 1 pili. Besides hybrid-type glycoasparagines from ovalbumin which were not active, large oligomannoside-type carbohydrate chains from legume storage glycoproteins moderately inhibited hemagglutinations, whereas the short oligomannoside-type glycoasparagine from ovalbumin Man alpha(1----6) [Man alpha(1----3)]Man alpha(1----6)[Man alpha(1----3)] Man beta(1----4)GlcNAc beta(1----4)GlcNAc beta(1----N)Asn exhibited a potent activity. These results strongly suggested that the nonsubstitution of the alpha(1----3)-linked mannosyl residue from the N-linked glycopeptide core structure is the key determinant in the minimal structural requirement specific to this fimbrial lectin. Such Man5GlcNAc2-containing glycopeptides were obtained from larger N-linked carbohydrate chains, occurring abundantly in natural sources. The ability of jack bean alpha-mannosidase to cleave the alpha(1----2)-linked mannoses more rapidly than the others allowed the controlled digestion of large oligomannoside-type glycopeptides from legume storage glycoproteins. Such shortened glycopeptides of plant origin were prepared which strongly inhibited guinea pig erythrocyte agglutinations as well as bacterial adhesion on human buccal cells, thus confirming their similarity (if not identity) with the receptor of type 1 pili on mammalian cells. The importance of this preparation of a receptorlike compound that inhibits bacterial adhesion with regard to the research on the role of type 1 pili in E. coli pathogenicity is discussed.