Glycosylation and biogenesis of a family of serine-rich bacterial adhesins

Abstract

Glycosylation of bacterial proteins is an important process for bacterial physiology and pathophysiology. BothO- andN-linked glycan moieties have been identified in bacterial glycoproteins. TheN-linked glycosylation pathways are well established in Gram-negative bacteria. However, theO-linked glycosylation pathways are not well defined due to the complex nature of knownO-linked glycoproteins in bacteria. In this review, we examine a new family of serine-richO-linked glycoproteins which are represented by fimbriae-associated adhesin Fap1 ofStreptococcus parasanguinisand human platelet-binding protein GspB ofStreptococcus gordonii. This family of glycoproteins is conserved in streptococcal and staphylococcal species. A gene cluster coding for glycosyltransferases and accessory Sec proteins has been implicated in the protein glycosylation. A two-step glycosylation model is proposed. Two glycosyltransferases interact with each other and catalyse the first step of the protein glycosylation in the cytoplasm; the cross-talk between glycosylation-associated proteins and accessory Sec components mediates the second step of the protein glycosylation, an emerging mechanism for bacterialO-linked protein glycosylation. Dissecting the molecular mechanism of this conserved biosynthetic pathway offers opportunities to develop new therapeutic strategies targeting this previously unrecognized pathway, as serine-rich glycoproteins have been shown to play a role in bacterial pathogenesis.