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. Both O-and N-linked glycan moieties have been identified in bacterial glycoproteins. The N-linked glycosylation pathways are well established in Gram-negative bacteria. However, the O-linked glycosylation pathways are not well defined due to the complex nature of known O-linked glycoproteins in bacteria. In this review, we examine a new family of serine-rich O-linked glycoproteins which are represented by fimbriae-associated adhesin Fap1 of Streptococcus parasanguinis and human platelet-binding protein GspB of Streptococcus 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 bacterial Olinked 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.

Mechanism of a cytosolic O -glycosyltransferase essential for the synthesis of a bacterial adhesion protein

“…Specifically, O-glycosylation is required for the biogenesis and function of adhesins of streptococci and staphylococci bacteria (9). These adhesins contain serine-rich repeats (SRR) that are heavily modified.…”

“…O-glycosylation plays a prominent role in the pathogenicity of Gram-positive bacteria and mycobacteria (8,9). Specifically, O-glycosylation is required for the biogenesis and function of adhesins of streptococci and staphylococci bacteria (9).…”

Glycosyltransferase-mediated Sweet Modification in Oral Streptococci

“…Fap1, the first SRRP identified, functions as an important bacterial adhesin (Stephenson et al 2002). The glycosylation of Fap1 is critical for biofilm formation and bacterial colonization (Zhou and Wu 2009). …”

“…Disruption of a balanced bacterial community leads to the development of oral infectious diseases. The initial adherence of early colonizers through glycosylated adhesins such as serine-rich repeat proteins (SRRPs) (Zhou and Wu 2009;Lizcano et al 2012) and other glycoconjugates plays an important role in the formation of dental plaque (Koo et al 2010;Falsetta et al 2014).…”

“…The glycosidic bond formation catalyzed by glycosyltransferases occurs between carbohydrate and acceptor. The acceptor is diverse, containing a variety of biomolecules such as serine-rich repeats or partially glycosylated serine-rich repeat proteins (Wu, Zeng, et al 2007;Bu et al 2008;Zhou and Wu 2009;Zhou et al 2010;Zhu et al 2011;Lizcano et al 2012), glucan matrix synthesized by cariogenic Streptococcus mutans (Lemos et al 2013), glycolipids (Ito et al 2011), and receptor polysaccharide (Xu et al 2003).…”