Periodontal disease is a significant global public health
concern and is probably the most common chronic infectious disease of humans.
The importance of bacteria in dental plaque and its key role in the causation of periodontal disease is well established.
It is clear that some organisms, such as P. gingivalis, A. actinomycetemcomitans, spirochetes, and P. intermedia, are strongly associated with a number of periodontal diseases. However, periodontal disease never occurs in the absence of a complex microbiota and it is often difficult , if not impossible, to determine precisely how different organisms contribute to an individual case of disease. NON-SPECIFIC PLAQUE HYPOTHESIS
SPECIFIC PLAQUE HYPOTHESIS
ECOLOGIC PLAQUE HYPOTHESIS Difficulties exist in the application of Koch's postulates to case of periodontitis, three primary problems are:
(1) the inability to culture all the organisms that have been associated with disease (e.g., many of the oral spirochetes) (2) the difficulties inherent in defining and culturing sites of active disease, and (3) the lack of a good animal model system for the study of periodontitis
In fact, if the ecologic plaque hypothesis proves correct, it must be inherently impossible to fulfill Koch's postulates, since no single organism or group of organisms is responsible for all cases of disease.
According to these criteria, a potential pathogen must do the following: Be associated with disease, as evident by increases in the number of organisms at diseased sites. Be eliminated or decreased in sites that demonstrate clinical resolution of disease with treatment Induce a host response, in the form of an alteration in the host cellular or humoral immune response Be capable of causing disease in experimental animal models Produce demonstrable virulence factors responsible for enabling the microorganism to cause destruction of the periodontal tissues.
Targeting one or more pathogens will not necessarily cure disease, since other organisms with similar activities might take their place.
It may make sense therefore to focus on the specific molecules that contribute to disease (virulence factors), rather than on the microorganisms that produce them.
The properties of a microorganism that enable it to cause disease are referred to as virulence factors
In fact , it is often difficult to separate the virulence determinants from the organisms that produce them.
For example, adhesins are produced by commensal organisms, as well as by pathogens, yet only those adhesins that promote attachment of a pathogenic organism could be considered virulence determinants. With this in mind, some of the known or putative virulence factors for periodontal disease are described below. It is important to note the following:
1. Only a proportion of periodontal bacteria have ever been isolated, and there are almost certainly many other virulence factors that are currently unknown .
2. Most of our understanding of virulence factors has come from studies on a very limited number of bacterial species and strains. It is far from clear that the molecules that have been studied in the greatest detail are truly representative of their classes.
1. Factors that promote colonization (adhesion & invasion) 2. Mechanisms that protect pathogenic bacteria from the host 3. Microbial Mechanisms of Host Tissue Damage Bacterial species that colonize gingival sulcus and periodontal pocket in this region must attach to available surfaces to avoid displacement by the gingival crevicular fluid flow. Therefore, adherence represents a virulence factor for periodontal pathogens.
The initial colonizers the periodontal environment most likely attach to the pellicle-or saliva-coated tooth surface. Eg. adherence of Actinomyces viscosus and Porphyromonas gingivalis through FIMBRIAE on the bacterial surface to proline- rich proteins found on saliva-coated tooth surfaces.
Through its fimbriae, P. gingivalis also binds to epithelial cells and fibroblasts.
Bacterial attachment to pre-existing plaque : COAGGREGATION eg: adherence of A. viscosus (fimbriae) to Streptococcus sanguis (polysaccharide receptor)
Bacterial adherence to host tissues likely plays a role in colonization and may be a critical step in the process of bacterial invasion.
Thus the ability of P. gingivalis to attach to other bacteria, epithelial cells, and the connective tissue components fibrinogen and fibronectin are all likely to be important in the virulence of this microorganism. It has been demonstrated that bacteria is present in periodontal tissues in : Gingivitis Necrotizing ulcerative gingivitis (NUG) Aggressive Periodontitis (both localized and generalized)
Both gram-positive and gram-negative bacteria, including cocci, rods, filaments, and spirochetes, have been observed in gingival connective tissue and in proximity to alveolar bone.
Bacteria may enter host tissues through -ulcerations in the epithelium of the gingival sulcus or pocket. -direct penetration of bacteria into host epithelial or connective tissue cells. eg, Aa, Pg, Fn & Td invade host tissue cells directly.
The clinical significance of bacterial invasion is not clear.
Bacterial species that have been identified as capable of tissue invasion are strongly associated with disease & has been proposed as a key factor that distinguishes pathogenic from non-pathogenic bacteria.
Localization of bacteria to the tissues provides an ideal position from which the organism can effectively deliver toxic molecules and enzymes to the host tissue cells, and this may be the significance of invasion as a virulence factor. It has been speculated that the bursts of disease activity observed in periodontitis may be related to phases of bacterial invasion of the tissues.
Provide a reservoir for recolonization which indicates the use of systemic antibiotics in combination with surgical therapy to eliminate Aa from lesions with localized aggressive periodontitis (LAP).
To survive in the periodontal environment, bacteria must neutralize or evade the host mechanisms involved in bacterial clearance and killing.
Bacterial adherence (allows bacteria to avoid displacement by host secretions) and invasion (disrupts the natural barriers formed by host tissue cells) are representative strategies by which microorganisms accomplish this task.
Periodontal bacteria neutralize or evade host defenses through numerous other mechanisms. For example, -Immunoglobulins
immunoglobulin-degrading proteases
opsonization of bacteria specific microorganisms
restricting bacterial adhesion produce substances
phagocytosis
suppress the activity of or kill PMNs and lymphocytes
- Aa of two toxins (a leukotoxin and cytolethal distending toxin) that may be important in the virulence of this microorganism in aggressive periodontitis and possibly in chronic periodontitis.
- Similarly, Tf & Fn have been shown to induce apoptosis in lymphocytes. (-) Microorgamisms Directly in degradation of host tissue Indirectly by release of biologic mediators from host tissue cells Some bacterial products inhibit the growth or alter the metabolism of host tissue cells; these include a number of metabolic byproducts such as ammonia; volatile sulfur compounds; and fatty acids, peptides, and indoles. enzymes produced by periodontal microorganisms eg. trypsinlike enzymes, induction of host tissue proteinases such as elastase and matrix metalloproteinases (MMPs) Release of IL-1, TNF and prostaglandins from monocytes, macrophages, and PMNs exposed to bacterial endotoxin (lipopolysaccharide). have the potential to stimulate bone resorption and activate or inhibit other host immune cells. Periodontal pathogens or their pathogenic products must be able to pass through the epithelial cell barrier in order to reach and cause destruction to underlying tissues (the gingiva, cementum, periodontal ligament and alveolar bone).
Once the organisms are firmly established in the gingiva, the host responds to the bacterial onslaught, especially to the bacterial lipopolysaccharide, by a marked and continual inflammatory response, which results in the destruction of the periodontal tissues.
Periodontal pathogens possesses so many virulence factors but unfortunate that only a few have been extensively studied. If we hope to understand and eradicate this pathogen, it is critical that in-depth investigations into the biochemistry, genetic expression, regulation and mechanisms of action of these factors be initiated.