Oral streptococci: modulators of health and disease

Abstract

Streptococci are primary colonizers of the oral cavity where they are ubiquitously present and an integral part of the commensal oral biofilm microflora. The role oral streptococci play in the interaction with the host is ambivalent. On the one hand, they function as gatekeepers of homeostasis and are a prerequisite for the maintenance of oral health - they shape the oral microbiota, modulate the immune system to enable bacterial survival, and antagonize pathogenic species. On the other hand, also recognized pathogens, such as oral Streptococcus mutans and Streptococcus sobrinus, which trigger the onset of dental caries belong to the genus Streptococcus. In the context of periodontitis, oral streptococci as excellent initial biofilm formers have an accessory function, enabling late biofilm colonizers to inhabit gingival pockets and cause disease. The pathogenic potential of oral streptococci fully unfolds when their dissemination into the bloodstream occurs; streptococcal infection can cause extra-oral diseases, such as infective endocarditis and hemorrhagic stroke. In this review, the taxonomic diversity of oral streptococci, their role and prevalence in the oral cavity and their contribution to oral health and disease will be discussed, focusing on the virulence factors these species employ for interactions at the host interface.

Keywords: Streptococcus sp.; biofilm; host interaction; oral diseases; virulence factors.

Figure 1

Immunomodulatory effects of oral commensal streptococci. The ability to form biofilms on numerous substrates can be regarded as a hallmark of oral streptococci. From within oral biofilms, streptococci interact with immune and epithelial cells, enable pathogens to co-adhere, and can disseminate into the blood stream. Modulation of the immune response to the bacterial biofilm challenge enables their persistence and survival in the host and determines the balance between immune homeostasis and dysbiosis. Specifically, through the downregulation of pro-inflammatory immune responses, oral streptococci contribute to a balanced immune status. Induction of hBD-2 released e.g., by S. mitis counteracts colonization by pathogenic species. This commensal was also found to induce a pro-inflammatory immune response in monocytes, while at the same time inhibiting neutrophil activity and T cell proliferation through the action of IL-10, PD-L1 and PGE2. In the context of systemic disease, it is beneficial for many streptococcal species that they can evade complement mediated immunity and thereby remain under the radar. Especially in periodontal disease, the role of oral streptococci to adhere to numerous substrates as primary colonizers and biofilm builders makes them a contributing factor to disease development, since they enable colonization of pathogenic species.

Figure 2

Streptococcal factors at the host interface. Cell wall-associated and secreted factors are depicted in the schematic representation of an oral Streptococcus sp. Gtf*, glycosyltransferases - GtfB and GtfC are cell wall associated, GtfD is secreted – Spx – streptococcal pyruvate oxidase. AgI/II – antigen I/II, Srr – serine-rich repeat protein, CSP – competence stimulating peptide, SWAN – cell-wall associated nuclease, RGP – rhamnose-glucose polymer, LTA – lipoteichoic acid, Cnm - surface glycoprotein Cnm with collagen- and laminin- binding capability.