Introduction/Definitions
Dental caries (tooth decay): dental caries is the most common infectious disease and involves the dissolution of solid tooth surface due to the metabolic action of bacteria. Deeper lesions can result in infection in the soft tissue inside the tooth, called the pulp, which contains blood vessels and nerves. These deeper infections lead to pain, referred to as a “toothache”.
Periodontal diseases:
Periodontal diseases are bacterial associated inflammatory diseases of the supporting tissues of the teeth and range from the relatively mild form of gingivitis to the more aggressive forms which are characterised by the destruction of the tooth’s supporting structures. Periodontitis is associated with a subgingival infection of a consortium of specific Gram-negative bacteria that leads to the destruction of the periodontium and is a major public health problem. One bacterium of interest is Porphyromonas gingivalis. Tooth loss is the ultimate determinetal effect of destructive periodontal disease.
Using culture independent 16S rRNA gene sequencing, it has been shown that the composiiton of the microbial community, rather than single organisms, relates directly to risk of dental caries or periodontitis. When the polymicrobial biofilms consist of the right combination of bacteria, such as the anaerobes Tannerella forsythia, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, the periodontal destruction process starts. The most common predisposing condition occurs when the plaque becomes mineralized (calcified) with calcium phosphate crystals. This process produces a hard, porous substance called calculus above and below the gingival margin (edge) that can induce varying degrees of periodontal damage.
Periodontal disease represents a group of oral inflammatory infections initiated by oral pathogens which exist as a complex biofilms on the tooth surface and cause destruction to tooth supporting tissues. The severity of this disease ranges from mild and reversible inflammation of the gingiva (gingivitis) to chronic destruction of connective tissues, the formation of periodontal pocket and ultimately result in loss of teeth. While human subgingival plaque harbors more than 500 bacterial species, considerable research has shown that Porphyromonas gingivalis, a Gram-negative anaerobic bacterium, is the major etiologic agent which contributes to chronic periodontitis. This black-pigmented bacterium produces a myriad of virulence factors that cause destruction to periodontal tissues either directly or indirectly by modulating the host inflammatory response. Here, this review provides an overview of P. gingivalis and how its virulence factors contribute to the pathogenesis with other microbiome consortium in oral cavity. See Chan
Etiologic Agents/Pathogenesis:
Steptococcus mutans:
An oral alpha hemolytic streptococcus, Streptococcus mutans, was long thought to be the primary cause of dental caries. More recent techniques points to a polymicrobial consortium of bacteria that contributes to the desructive acid production. In the absence of dietary carbohydrates, bacteria do not cause decay. In the presence of sucrose and, to a lesser extent, other carbohydrates, S. mutans and other streptococci produce sticky polymers of glucose called fructans and glucans. These adhesives help bind them to the smooth enamel surfaces and contribute to the sticky bulk of the plaque biofilm. If mature plaque is not removed from sites that readily trap food, it can result in a carious lesion. This is due to the ratio of the streptococci and other bacteria that produce acid as they rement the carbohydrates. If the acid is immediately flushed from the plaque and diluted in the mouth, it has little effect. However, in desner region of plaque, the acid can accumulate in direct contact with the enamel surface and lower the pH to below 5, which is acidic enough to beign to dissolve (decalcify) the calcium phosphate of the enamel in the spot.
Actinobacillus actinomycetemcomitans is the principal etiologic agent of early onset periodontitis but other select microorganisms also play a role. For example, Streptococcus mutans attaches to glucans deposited on the tooth surface. Such attachment is believed to enhance the ability of S. mutans to metabolize dietary sucrose to acid, which then can destroy tooth enamel and eventually result in a carious lesion. S. mutans and other oral streptococci use a surface protein called glucan-binding lectin (GBL) to attach to surface-bound glucan.
Porphyromonas gingivalis (P. gingivalis) is a black pigmented, anaerobic, proteolytic Gram-negative rod that obtains energy from the metabolism of specific amino acids. It has an absolute growth requirement for iron, preferentially in the form of heme or its Fe(III) oxidation product hemin. US 6,528,038 discloses antigens from P. gingivalis used for raising an immune response against P. gingivalis.
In normal individual, primarily gram positive flora. Upon infection or disease, shift to gram negative organisms. Majority of pathogology due to P. gingivalis (gram negative).
P. gingivalis infection stimulates TLR2 epxression on mouse macrophages but not TLR4. TLR2 is Required for P. gingivalis Mediated Oral Bone Loss. TLR2-deficient mouse macrophages fail to stimulate P. gingivalis mediated artheroscloerosis.
Streptococcus gordonii: a Gram-positive bacterium, is a commensal bacterium that is commonly found in the skin, oral cavity, and intestine. It is also known as an opportunistic pathogen that can cause local or systemic diseases, such as apical periodontitis and infective endocarditis. S. gordonii, an early colonizer, easily attaches to host tissues, including tooth surfaces and heart valves, forming biofilms. S. gordonii penetrates into root canals and blood streams, subsequently interacting with various host immune and non-immune cells. The cell wall components of S. gordonii, which include lipoteichoic acids, lipoproteins, serine-rich repeat adhesins, peptidoglycans, and cell wall proteins, are recognizable by individual host receptors. They are involved in virulence and immunoregulatory processes causing host inflammatory responses. Therefore, S. gordonii cell wall components act as virulence factors that often progressively develop diseases through overwhelming host responses. This review provides an overview of S. gordonii, and how its cell wall components could contribute to the pathogenesis and development of therapeutic strategies. See Han
Apical periodontitis is mainly caused by bacterial invasion into the dental pulp and endodontic lesions, and the attachment of bacteria on dentin surfaces is a critical step for the development of apical periodontitis. S. gordonii expresses numerous cell wall proteins that facilitate attachment on dentin surfaces. After successful attachment, S. gordonii forms biofilm matrix by deposition of extracellular polysaccharide, which is an essential structural component of biofilm. S. gordonii found in biofilms is more resistant to antibacterial agents than in the planktonic state, making it harder to eliminate S. gordonii. See Han
The interaction subsequently induces inflammatory conditions on periapical lesions. For instance, S. gordonii induces the expression and secretion of chemotactic cytokines called interleukin (IL)-8 by stimulating toll-like receptor (TLR) 2 of human periodontal ligament cells (PDLs). In fact, S. gordonii lipoprotein triggers the secretion of IL-8, monocyte chemoattractant protein (MCP)-1, cyclooxygenase-2, and prostaglandin E2 in the human dental pulp cells.
S. gordonii, released from oral biofilms by tooth brushing, tooth extraction, or oral trauma, can disperse into the circulatory system through blood vessels, leading to systemic infections. Infective endocarditis is a life-threatening disease caused by oral streptococci where the hospital mortality rate from this disease counts approximately 20%.
Biofilm Formation:
The oral cavity provides a habitat for about 700 microbial speceis forming complex and dynamic multispecies biofilams, asl referred to as “dental plaque”. The oral Gram-negative anaerobic bacteria P. gingivalis is typically a late colonizer of subgingival biofilms and has been correlated with several destructive periodontal dsieases, including periodontitis and peri-implantitis. P. gingivalis pathogenicity is reflected in an arsenal of virulence factors involved in tissue colonization and destruction, and interference with host defense systems. Bioflm development is a complex, multi-stage process. Initially, bacteria adhere to abiotic or biotic surfaces by production of surface appendages. Next, biofilms mature by the development of a three-diemnsional structure containing microcolonies in which different species can itneract with each other (biofilm maturation). In the last phase, cell disperse form the biofilm, allowing the formaiton of new fiofilms (biofilm dispersal) About 18% of the P. gingivalis genome is differentially expressed when the bacteria is grown as a biofilm, demonstrating the complexity of biofilm development. Given the side vareity of substrates to which P. gingivalis can attach in the oral cavity (e.g., oral soft tissues, implant materials, and other bacteria), many extracellular structures play a role in mediating specific and stable substrate attachment. Examples include fimbriae, LPS and capsules. Quorum sensing is a bacterial communicaton mechanisms in which the expression of genes is coordinated through the accumualtion of specific signaling molecules. This quarum sensing system has been shwon to play a role in interspecies communicaiton of P. gingivalis. (Michiels, “New approaches to combat Porphyromonas gingivalis biofilm” J or Oral Microbiology, vol 9, 2017).
P. gingivalis is one of the most prevalent bacteria in periodontitis, a chronic inflammatory disease of the oral cavity. The disease is characterized by destruction of the supporting structures of the teeth (ie., the gingiva, the periodontal ligament and the alveolar bone) and can eventually lead to loss of teeth. Furthermore, periodontitis has recently been associated with an increased risk for delivery of premature labor and low birth weight infants. P. gingivalis is also recognized as a kestone pathogen in perio-implantitis, a periodontal disease characterized by inflammation of the hard and soft tissues surrounding dental implants. When oft untreated, peri-implantitis can result in loss of the dental implant. (Michiels, “New approaches to combat Porphyromonas gingivalis biofilm” J or Oral Microbiology, vol 9, 2017).
–Biofilm Control: There are many conventional methods to regulate biofilm. Especially for oral biofilm, physical removalby tooth brushing and scaling, is one of the most effective strategies to disrupt the biofilm. Several studies have demonstrated that tooth brushing results in an attenuation of plaque level. In addition, many other studies have revealed that various techniques of scaling, such as hand and ultrasonic scaling, laser scaling, and chemical scaling, have been used to control plaques. Another traditional method to control biofilm is through the use of various chemicals, such as CHX, sodium chloride, and calcium chloride. CHX is a potential antimicrobial agent, which participates in disrupting biofilms by binding to negatively charged bacterial cell walls. Salts, such as sodium chloride and calcium chloride, may weaken electrostatic interactions and, therefore, can attenuate the biofilm matrix. See Han
Using small molecules that suppress quorum sensing-mediated bacterial communication is in the spotlight as a novel therapeutic strategy for regulating biofilm. By using quorum sensing inhibitors, it is expected biofilm maturation can be easily regulated and bacterial self-protection attenuated from antimicrobial agents furnished by a mature biofilm. See Han
Virulence factors: In order to survive and multiply in a host, the invading pathogen needs to overcome the host external protective barriers before it could find a suitable ecological niche for colonization. Colonization of the host tissues could only happen in the presence of virulence factors such as fimbriae, capsules, lipopolysaccharide (LPS), lipoteichoic acids, haemagglutinins, gingipains, outer membrane proteins, and outer membrane vesicles.
The cell envelope of Gram-negative bacteria such as Porphyromonas sp. comprises of two cell membranes, the outer membrane (OM) and the inner membrane (IM). Both layers of membranes have different composition and structure. They are separated by the periplasm containing the peptidoglycan layer. While the IM is a phospholipid bilayer with numerous integral IM proteins, the OM is an asymmetrical bilayer which consists of phospholipids and lipopolysaccharide in the inner and outer leaflet, respectively. The bacterial cell membrane plays a role as the selective barrier that offers protection and allows the movements of various substances through OM porin proteins.
Treatment Strategies:
Most periodontal disease is treated by removal of calculus and plaque and maintainace of good oral hygiene. Often, surgery to reduce the depth of periodontal pockets is required. Antibiotic therapy, either systemic or applied in periodontal packings, may also be sued.
Treatment procedures of P. gingivalis-mediated diseases such as periodontitis and peri-implantitis focus on the eradication of oral pathogens at the site of infection, usually by surface debredement procedures followed by adjunctive therapies, including the use of antiseptics or/and antbiotics. (Michiels, “New approaches to combat Porphyromonas gingivalis biofilm” J or Oral Microbiology, vol 9, 2017).
Chlorhexidine: is an antiseptic that has been widely used in dental practice becasue of its broad specturm ani-microbial activity. Local applicaotn of chlorhexidine can be done in the form of gels, chips, mothwashes or films. Despite its wiedspread use, some limtiations include brown discoloration of the teeth, supraginigival calculus formation and more rarely oral mucosal erosion and parotid swelling. (Michiels, “New approaches to combat Porphyromonas gingivalis biofilm” J or Oral Microbiology, vol 9, 2017).
Antibiotiocs: Several antibiotic classes have also been suggested for the treatment of P. gingivalis related infections including tetracyclines (tetracycline hydrochloride, minocycline, doxycycline), macrolides (erythromycin), lincosamides (clindamycin), beta-lactams (ampicillin, amoxicillin) and nitroimidazoles (methronidazole). These antibiotics can be administered by either local or systemic routes. Local adminsitraiton has the advantage that higher therapeutic concentraiton of antibiotics can be delivered inside the pocket, avoidng some of the side effects of systemic adminsitration. (Michiels, “New approaches to combat Porphyromonas gingivalis biofilm” J or Oral Microbiology, vol 9, 2017).
Quorum sensing inhibitors: have been presented as promising alternative for the treatment of biofilm-related infections, as they do not affect grwoth and thus have a low potential for resistance development. In this respect, quorum sensing inhbitors have been shown to reduct both P. gingivalis monospecies and F. nucleatum and P. gingivalis mixed-species biofilm development. (Michiels, “New approaches to combat Porphyromonas gingivalis biofilm” J or Oral Microbiology, vol 9, 2017).
Antimicrobial peptides: are widely proposed as a new source of future antibiotics, as they often ahve braod spectrum activity and a low tendency for resistance devleopment. (Michiels, “New approaches to combat Porphyromonas gingivalis biofilm” J or Oral Microbiology, vol 9, 2017).
Plant-dervived antibacterial agents: The non-dialyzable material fraction of cranberry uice rich in proanthocyanidins and A-type cranberry proanthocyanidins extracted form cranberry juice concentraiton were shown to exhibit activity against P. gigivalis. A number of prenylated flavonoids isoalted from Epimedium species were reproted to inhibit biofilm formation by P. gingivalis. Licinatrin dervied form Citrus fuiits and tea catechin dervied form Cameilia sinesis have been desmonstrated to inhibit biofilm formation of P. gingivalis biofilms and to desorb pre-formed biofilms. Extracted oils obtained from plants also posses activity against P. gingivalis biofilms. (Michiels, “New approaches to combat Porphyromonas gingivalis biofilm” J or Oral Microbiology, vol 9, 2017).
Screening of compound libraries has resulted in the identification of new antibacterial agents that show activity agaisnt P. gingivalis. For example, a screen from a compound library in search for new molecules that exhibit activity agaisnt the opportunistic pathogen Pseudomonas aeruginosa identified a dichlorocarbazol derivative as a new antibacterial agent with road spectrum activity, including activity agaisnt P. gingivalis biofilms. In another study, a library of small molecuels based on 2-aminoimidazole and 2-aminobenzimidazole scaffolds were screened with the aim of identifying compounds that could inhibit co-colonizaiton of P. gingivalis and S. gordonii. In this screening, three small molecuels derived from oridin and cotnaining 2-aminoimidazole or 2 aminobenzimidazole moieties were identifed. These compounds inhibt co-colonization by reducing expression of both mfa1 and fimA fimbrial genes in P. gingivalis. (Michiels, “New approaches to combat Porphyromonas gingivalis biofilm” J or Oral Microbiology, vol 9, 2017).
Products
Toobrushes: Water Pik Sonic-fusion (toothbrush and waterpik at same time)