Streptococcus sanguinis biofilm formation & interaction with oral pathogens

Abstract

Caries and periodontitis are the two most common human dental diseases and are caused by dysbiosis of oral flora. Although commensal microorganisms have been demonstrated to protect against pathogens and promote oral health, most previous studies have addressed pathogenesis rather than commensalism. Streptococcus sanguinis is a commensal bacterium that is abundant in the oral biofilm and whose presence is correlated with health. Here, we focus on the mechanism of biofilm formation in S. sanguinis and the interaction of S. sanguinis with caries- and periodontitis-associated pathogens. In addition, since S. sanguinis is well known as a cause of infective endocarditis, we discuss the relationship between S. sanguinis biofilm formation and its pathogenicity in endocarditis.

Keywords: Streptococcus sanguinis; biofilm; oral microbiota.

Figure 1.. Impact factors of biofilm formation in Streptococcus sanguinis.

(A) Pioneer S. sanguinis bacterium (orange) recognizing tooth surface salivary pellicle receptors (pink and blue) and forming initial bonds. Model shows recognition of multiple types of attachment receptors including long-range attachment, for example, fimbriae (orange) which can bind to multiple salivary components (blue) and SsaB (green) which may mediate attachment to saliva-coated hydroxyapatite via an uncharacterized pH-sensitive receptor (pink). (B) The response regulator CiaR of the CiaRH two-component system can inhibit the expression of ArgB which in turn leads to the upregulation of gtfP. Upregulation of gtfP can also be triggered by the deletion of BrpT. An increase in GtfP promotes the synthesis of glucan which enhances biofilm formation. The two-component system VicRK regulates the expression of pyruvate oxidase SpxB. Upregulation of SpxB will increase H₂O₂ and vice versa. Increased H₂O₂ induces cellular autolysis and subsequent eDNA release. Deletions in PurB, PurL, PyrE, ThrB, AdcA, Spi and SptRS, all show a decrease in biofilm formation. Exogenous L-arginine has been shown to decrease biofilm formation with mechanisms unknown.

Figure 2.. Mechanisms of antagonism between Streptococcus sanguinis and Streptococcus mutans.

(A) H₂O₂ generated by Streptococcus sanguinis inhibits the growth of Streptococcus mutans and itself. Enzymes for reactive oxygen species degradation are produced by both species to increase their H₂O₂ resistance. Mutacins are synthesized by S. mutans to suppress the growth of S. sanguinis. CSP of S. mutans is necessary for mutacins production and can be inactivated by S. sanguinis. (B) S. mutans can generate acids from fermentable sugars to induce dental caries. However, the pH homeostasis may be maintained by the arginine deiminase system of S. sanguinis to prevent against dental caries. (C) L-arginine treatment decreases the biomass of S. mutans more than that of S. sanguinis. ADS: Arginine deiminase system; CSP: Competence-stimulating peptide; SOD: Superoxide dismutase; STPK: Serine/threonine protein kinase.

Figure 3.. Interaction of Streptococcus sanguinis with periodontitis-associated pathogens.

Fusobacterium nucleatum can attach to Streptococcus sanguinis via RadD or Aid1. Aid1 attachment is mediated by RadD. Both interactions can be inhibited by the presence of arginine. Porphyromonas gingivalis can attach to S. sanguinis by fimbriae to surface glyceraldehyde-3-phosphate dehydrogenases receptors. P. gingivalis can attach to Streptococcus gordonii using small fimbriae made from the adhesin Mfa1. Perhaps this mechanism is also utilized for attachment to S. sanguinis. However, it is known that S. sanguinis can suppress the expression of the mfa1 gene. Aggregatibacter actinomycetemcomitans colonization of epithelial cells in a flow chamber will be repressed by the colonization of S. sanguinis.