The Pathogenic Factors from Oral Streptococci for Systemic Diseases

Abstract

The oral cavity is suggested as the reservoir of bacterial infection, and the oral and pharyngeal biofilms formed by oral bacterial flora, which is comprised of over 700 microbial species, have been found to be associated with systemic conditions. Almost all oral microorganisms are non-pathogenic opportunistic commensals to maintain oral health condition and defend against pathogenic microorganisms. However, oral Streptococci, the first microorganisms to colonize oral surfaces and the dominant microorganisms in the human mouth, has recently gained attention as the pathogens of various systemic diseases, such as infective endocarditis, purulent infections, brain hemorrhage, intestinal inflammation, and autoimmune diseases, as well as bacteremia. As pathogenic factors from oral Streptococci, extracellular polymeric substances, toxins, proteins and nucleic acids as well as vesicles, which secrete these components outside of bacterial cells in biofilm, have been reported. Therefore, it is necessary to consider that the relevance of these pathogenic factors to systemic diseases and also vaccine candidates to protect infectious diseases caused by Streptococci. This review article focuses on the mechanistic links among pathogenic factors from oral Streptococci, inflammation, and systemic diseases to provide the current understanding of oral biofilm infections based on biofilm and widespread systemic diseases.

Keywords: Biofilm; Oral infection; Pathogenic factor; Streptococci; Systemic Diseases.

Figure 1

Life style of biofilm and the conceptual pathogenic mechanisms of oral bacterial infection leading to various systemic diseases.

Figure 2

The phylogenetic relationship among 8 major groups of human Streptococcal species.

Figure 3

A clinical case of infective endocarditis caused by oral Streptococcus sanguinis. A 72 years-old male patient with mitral and tricuspid regurgitations was urgently hospitalized for continuous fever over 37 °C and diagnosed as infective endocarditis by detection of oral Streptococcus, S. sanguinis. During the hospitalization for 1 month, patient received viccilin (ampicillin sodium: 6000 mg/day) and gentamicin (a type of aminoglycoside: 60 mg/day). After the improvement of symptoms and no bacterial detection by blood culture, patient underwent artificial valve replacement and tricuspid ring annuloplasty, and then was discharged from hospital due to the stabilization of symptoms. The patient came to our dental department for the prevention of recurrence with a referral from the medical doctor. (a) Chest radiograph and echocardiogram at the time of the onset of infective endocarditis. Cardiac hypertrophy (Cardio-thoracic Ratio: CTR: ≥ 50%) was observed due to abnormalities in the mitral valve, and the left atrium was enlarged markedly. Vegetation (green arrow) was observed in the mitral valve. (b) Oral and X-ray photographs of patient with infective endocarditis. Gingival redness and slight swelling were observed in full mouth, and dental calculus deposition were observed on mandibular anterior teeth and upper left molars. Mobility of upper anterior teeth and left premolars was also observed. From dental X-ray radiographs, root fractures of upper right central and lateral incisors, and a endodontic-periodontal combined lesion of the upper left incisor and canines were found. Severe alveolar bone loss around the upper anterior teeth and left premolars as well as root caries on the upper lateral incisor and 1st premolar was also observed. The number of total Streptococci in 10 µL of saliva was 1.0 × 10 ⁷ copies and various periodontal pathogens, such as Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Tannerella forsythia, Treponema denticola and Fusobacterium nucleatum, were also detected at significantly high level.

Figure 4

Co-localization and distribution of eDNA and Si-HLP in S. intermedius biofilm. eDNA in the formed S. intermedius biofilm was stained with propidium iodide (PI; red fluorescence), and Si-HLP was stained with anti-Si-HLP antibody and Alexafluor 488 (green fluorescence). Fluorescence microscopic observation showed that eDNA and HLP are co-localized (yellow fluorescence) and uniformly distributed in biofilm.