Three glycosylated serine‐rich repeat proteins play a pivotal role in adhesion and colonization of the pioneer commensal bacterium, Streptococcus salivarius

Abstract

Bacterial adhesion is a critical step for colonization of the host. The pioneer colonizer and commensal bacterium of the human gastrointestinal tract, Streptococcus salivarius, has strong adhesive properties but the molecular determinants of this adhesion remain uncharacterized. Serine-rich repeat (SRR) glycoproteins are a family of adhesins that fulfil an important role in adhesion. In general, Gram-positive bacterial genomes have a unique SRR glycoprotein-encoding gene. We demonstrate that S. salivarius expresses three large and glycosylated surface-exposed proteins - SrpA, SrpB and SrpC - that show characteristics of SRR glycoproteins and are secreted through the accessory SecA2/Y2 system. Two glycosyltransferases - GtfE/F - encoded outside of the secA2/Y2 locus, unusually, perform the first step of the sequential glycosylation process, which is crucial for SRR activity. We show that SrpB and SrpC play complementary adhesive roles involved in several steps of the colonization process: auto-aggregation, biofilm formation and adhesion to a variety of host epithelial cells and components. We also show that at least one of the S. salivarius SRR glycoproteins is important for colonization in mice. SrpA, SrpB and SrpC are the main factors underlying the multifaceted adhesion of S. salivarius and, therefore, play a major role in host colonization.

Biology of Oral Streptococci

“…Among them, GspB and Hsa are serine-rich repeat glycoproteins (Srr) that bind to sialylated glycans present on the soluble human salivary mucin MG2/MUC7, a component of the mucosal pellicle (64), and the platelet glycoprotein GPIb (65, 66). Srr proteins are important for biofilm formation and have been identified in many other oral streptococci, including Fap1 of S. parasanguinis (67) and S.oralis (68), SrpA of S. sanguinis (69) and S. cristatus (70), and SrpA, B and C of S. salivarius (71). Interestingly, Srr homologs are not present in the caries pathogen S. mutans .…”

Osteopontin adsorption to Gram-positive cells reduces adhesion forces and attachment to surfaces under flow

“…Many adhesins belong to the superfamily of cell wall-anchored polypeptides with the C-terminal consensus motif LPxTz, including type I fimbriae of Actinomyces spp. [17], the streptococcal antigen I/II [18], and serine-rich repeat protein (SRRP) families [19][20][21][22][23]. In SRRP adhesins, which have been identified in both streptococci and lactobacilli [23], glycoconjugates play an important role for adhesion [21,24].…”

Enterococcus adhesin PrgB facilitates type IV secretion by condensation of extracellular DNA

“…The best-characterized SRRPs are from streptococcal species, such as from S. salivarius, a commensal of the human gastrointestinal tract, which expresses three large glycosylated surface exposed proteins, SrpA, SrpB and SrpC. These proteins were demonstrated to be very important for the adhesion process, thus playing a major role in host colonization (Couvigny et al, 2017). While less is known about plasmid-encoded adhesins from G+ bacteria, PrgA, PrgB and PrgC from pCF10 and Asa1 from pAD1, both from E. faecalis sex-pheromone responsive plasmids (Muscholl-Silberhorn, 1998;Süssmuth et al, 2000;Rozdzinski et al, 2001;Dunny, 2007;Bhatty et al, 2015;Dunny and Berntsson, 2016;Bhatty et al, 2017) definitely rank among the best-characterized key players in cellular adhesion and aggregation processes.…”