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

Benoit Couvigny,Alain Guillot,Michel‐Yves Mistou,Joel Doré,Romain Briandet,Thierry Meylheuc,Lionel Rigottier‐Gois,Eric Guédon,Pierre Renault,Manfred Rohde,Pascale Serror,Sophie Chat,Saulius Kulakauskas,Nicolas Lapaque

doi:10.1111/1462-2920.13853

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.

Highlights

The human body harbours a diverse and dense population of commensal bacteria, which exerts key functions in terms of nutrition and health
We show that at least one of the S. salivarius Serine-rich repeat (SRR) glycoproteins is important for colonization in mice
As in previously characterized SRR proteins, the SrpA/B/C sequences contained an atypical Nterminal signal peptide followed by a short SRR domain (SRR1), a ligand-binding region (BR) and a long SRR domain (SRR2) containing a cell wall anchoring motif (Fig. 1B) (Lizcano et al, 2012; Bensing et al, 2014)

Summary

Introduction

The human body harbours a diverse and dense population of commensal bacteria, which exerts key functions in terms of nutrition and health. Streptococcus salivarius is a ubiquitous human commensal bacterium that plays important roles in oral and in digestive tract ecology (Delorme et al, 2015) and in immune system modulation (Kaci et al, 2014; Couvigny et al, 2015b) This bacterium is one of the first bacterial species to colonize the mucosa in the first few days after birth (Pearce et al, 1995) and is maintained as a dominant population in the human oral cavity and upper airways throughout life (Nakajima et al, 2013). This diversity in isolate origins suggests that this bacterium has evolved various strategies to adapt and colonize multiple ecological niches in its human

Results

Discussion

Conclusion