Pseudomonas aeruginosa, a gram-negative bacterium, and Candida albicans, a dimorphic yeast, are evolutionarily distant microorganisms which can utilize filamentous structures termed pili and fimbriae, respectively, to mediate adherence to glycosphingolipids (asialoganglioside-GM1) receptors. The mechanism of adherence to glycosphingolipid receptors was investigated in these studies. By using monoclonal antibodies (MAbs) against purified pili of P. aeruginosa PAK (PK99H) and monospecific anti-peptide antibodies against the PAK pilin peptides [anti-PAK(128-144) and anti-PAK(134-140)], we demonstrated that these antibodies agglutinated C. albicans whole cells and cross-reacted with C. albicans fimbriae in immunoblots. A control MAb, PKL1, and anti-PAK(75-84) peptide antibodies failed to agglutinate C. albicans whole cells or cross-react with the fimbrial proteins. Conversely, the anti-C. albicans fimbrial MAb Fm16, but not Fm34, agglutinated P. aeruginosa PAK whole cells and Western blots (immunoblots). The interactions between PK99H and Fm16 and their respective homologous antigens were competitively inhibited by heterologous antigens; this demonstrated that the interactions between the antibodies and the heterologous antigens, i.e., PK99H with C. albicans fimbriae and Fm16 with P. aeruginosa pili, were highly specific and suggested that both adhesins share a common antigenic determinant. The immunological cross-reactivity between Fm16 and P. aeruginosa PAK pilin is localized onto the PAK(134-140) region as shown by a competitive enzyme-linked immunosorbent assay. The PAK(134-140) region of PAK pilin contains the epitope recognized by PK99H and also constitutes part of the receptor-binding domain of the pilus adhesin. Thus, the results from these studies suggest that common cell surface receptors are recognized by the P. aeruginosa and C. albicans adhesins because of a conserved receptor-binding domain on the adhesins.