Role of surface proteins SspA and SspB of Streptococcus gordonii in innate immunity

Abstract

Streptococcus gordonii, a normal inhabitant of the human oral cavity, is a potential live vaccine vehicle. Several pathogen-associated molecular patterns from S. gordonii that are recognized by antigen-presenting cells have recently been identified. In this study, we have identified that the cell-wall-anchored proteins SspA and SspB are immunostimulatory components of S. gordonii. SspA and SspB are members of the antigen I/II family of proteins widely expressed by viridans oral streptococci. The results showed that the mutant (OB219) lacking SspA and SspB had a reduced ability to induce cytokine/chemokine production in epithelial cells and bone-marrow-derived dendritic cells as compared with the parent strain (DL1). Purified SspA induced interleukin-6 and monocyte chemotatic protein-1 production from human lung epithelial A549 cells. The induction could be inhibited by a function-blocking anti-β1 integrin mAb and the purified SspA could bind to β1 integrin precoated on microtitre plates, suggesting that the induction was effected by SspA-β1 integrin interactions. The role of SspA and SspB in innate immunity was further demonstrated in a mouse intranasal challenge experiment, which showed that the clearance of OB219, the recruitment of neutrophils (as indicated by myeloperoxidase activity), and chemokine and cytokine production in the lungs of OB219-inoculated mice were delayed or reduced as compared with the DL1-inoculated mice. In addition to the above, S. gordonii OB219 was more sensitive to polymyxin, nisin and histatin-5 than DL1, suggesting that SspA and SspB also play a role in susceptibility to cationic antimicrobial peptides. Collectively, the results indicate that SspA and SspB are immunostimulatory components of S. gordonii and play an important role in modulating the host's innate immunity.

Human Salivary Protein Histatin 5 Has Potent Bactericidal Activity against ESKAPE Pathogens

“…Up to now, a few reports have described interactions between Hst 5 and bacteria. Hst 5 was found to have low killing against Streptococcus gordonii (a Gram-positive commensal bacterium of the human oral cavity; Andrian et al, 2012 ). Zinc-mediated killing of E. faecalis bacteria by histidine–rich histatin analogs was found (Rydengard et al, 2006 ), and killing activity of another histatin derivative (P113) against P. aeruginosa and S. aureus in vitro was shown (Giacometti et al, 2005 ).…”

Oral Microbiome and SARS-CoV-2: Beware of Lung Co-infection

“…Under certain conditions, Streptococcus gordonii can attack host fibronectin, and subsequent cytokine production can induce inflammatory responses ( Erb-Downward et al, 2011 ; Liu et al, 2018 ). The cell-wall-anchored protein Staphylococcal surface protein A (SspA), a key factor in regulating the host innate immunity, is an immunostimulatory component of S. gordonii that promotes bacterial adhesion, and purified SspA can induce IL-6 and monocyte chemotatic protein-1 production from human lung epithelial cells ( Andrian et al, 2012 ).…”

Influence of saliva on the oral microbiota

“…In gram‐positive bacteria, including S. mutans , the dlt operon mediates d ‐alanyl esterification of teichoic acids, which decreases the negative charge of the cell wall and reduces host defence peptide binding and killing . Sensitivity of S. gordonii to β‐defensin 2 and histatin 5 was increased by loss of expression of SspA and SspB, members of the multifunctional antigen I/II family of proteins expressed by oral streptococci . A range of oral bacteria, including streptococci, Neisseria spp., Actinomyces spp.…”