Study of glycosylation mechanism and virulence of glycoproteins produced by streptococci

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Streptococcus gordonii on the human tooth surface is associated with the formation of dental plaque and infectious endocarditis. We have previously reported that sialic acid-binding adhesin (Hsa) of this bacterium is a N-acetyl-glycosamine containing-glycoprotein, in which glycosylated region is Ser-rich repeat domain of Hsa, and is bound to glycol with O-glycosylation manner. An insertional mutation in hsa, the gene encoding Hsa, resulted in a significant reduction of the infection rate of the organism and an inflammatory reaction in the rat aortic valve with experimental endocarditis, suggesting that the Hsa contributes to the infectivity of the organism for heart valves. The contribution of the agglutination of platelet and erythrocyte on infectious endocarditis is estimated. We have 〓viously indicated that the receptor of platelet to Hsa of this bacterium is two kind of intrinsic membrane asialo-glycoprotein. We found that the interaction between Hsa and α2-3-linked sialic acid con … More tained by erythrocyte membrane proteins. We also confirmed that erythrocyte surface sialoglycoproteins, glycophorin A and band 3, are the receptor for Hsa. For finding the gene related to the glycosylation of Hsa, we have screened the transposon-mutation library of S. gordonii, and we identified the glmM gene encoding the phosphoglucosamine mutase which is concerned of the synthesis of cell wall in other bacteria. Insertional glmM mutant of this bacterium did not produce GlmM, and had a growth rate of about half of the wild type. Morphological analysis indicated that the glmM mutation causes elongation of the streptococcal chains, enlargement of bacterial cells, and increased roughness of the cell surface. Furthermore, glmM mutation reduces biofilm formation and increases sensitivity to penicillin relative to wild type. These results suggested that mutation in glmM appears to influence the phenotype relating to the peptidoglycan synthesis. We are now studying the relationship the function of GlmM and glycosylation of Hsa. Less