Chronic periodontitis is a bacterial-associated inflammatory disease of the supporting tissues of the teeth, which results in the destruction of tooth support and ultimately leads to tooth loss. The disease is a major public health problem with a large economic burden. The bacterium Porphyromonas gingivalis has been identified as a major pathogen in the development of chronic periodontitis. We have identified and characterised a major virulence factor of P. gingivalis; a complex of proteins whic ....Chronic periodontitis is a bacterial-associated inflammatory disease of the supporting tissues of the teeth, which results in the destruction of tooth support and ultimately leads to tooth loss. The disease is a major public health problem with a large economic burden. The bacterium Porphyromonas gingivalis has been identified as a major pathogen in the development of chronic periodontitis. We have identified and characterised a major virulence factor of P. gingivalis; a complex of proteins which is involved in binding and destruction of host tissue. We have shown that this protein complex when used as a vaccine protects against P. gingivalis induced disease in animal periodontitis models. We have identified the regions (peptides) of the protein complex that allow the bacteria to bind to host tissue and blood proteins and these and other complex-related peptides when used as vaccines reduced disease in animal models. Recently, a consortium involving T.denticola, T.forsythia and P.gingivalis has been closely associated with the development of periodontitis in humans. We have shown that a mixture of these bacteria have greater pathogenicity in an animal periodontitis model than any one bacterium individually at the same total dose. The aim of this project is to identify epitopes in T. denticola and T. forsythia and to combine them with those of P. gingivalis into a multipathogen vaccine using techniques we have patented. The efficacy of the multipathogen vaccine to produce an immume response which is effective against the three bacteria will be investigated. The significance of this work is that we will produce a fully synthetic vaccine that may have utility in the prevention of periodontitis and the platform technology developed may have utility for a range of diseases associated with multiple bacterial pathogens.Read moreRead less
Porphyromonas Gingivalis Cysteine Proteinases In Modulation Of Cell-mediated Immune Response In Periodontitis
Funder
National Health and Medical Research Council
Funding Amount
$228,000.00
Summary
Chronic inflammatory diseases of the tissues supporting the teeth comprise some of the most widespread and common diseases to affect mankind. Recent research has indicated the major contributor to the most common form of destructive periodontal disease is the bacterium Porphyromonas gingivalis. This organism produces powerful enzymes which overcome the body's attempts to neutralise them. It is also known that the destructive phase of the disease is characterised by a change in the behaviour of t ....Chronic inflammatory diseases of the tissues supporting the teeth comprise some of the most widespread and common diseases to affect mankind. Recent research has indicated the major contributor to the most common form of destructive periodontal disease is the bacterium Porphyromonas gingivalis. This organism produces powerful enzymes which overcome the body's attempts to neutralise them. It is also known that the destructive phase of the disease is characterised by a change in the behaviour of the immune system cells which accumulate in the diseased tissues. This is manifest as a loss of protective immunity and replacement by ineffective or even tissue damaging responses. Critical in directing the pattern of behaviour of the immune system cells are the potent messenger molecules or cytokines which pass between cells. We have demonstrated that the bacterial proteinases can destroy a critical messenger molecule that instructs the defensive phagocytic cells to attack bacteria. These cells in return normally send a powerful signal back to the controlling T lymphocyte to amplify the protective signals. Associated bacterial molecules stimulate more secretion of messenger molecules which are paradoxically destroyed by the bacterial enzymes. This could cause chaos in the local tissue environment. Further, the bacterial proteinases can also eliminate some important surface molecules of T lymphocyte that are important in the activation process. The effect of this could produce impairment of T lymphocyte at periodontal sites. The planned research will define how the proteinases modulate T lymphocyte immune response. Further, the relation between the capacity of the bacterial enzymes to disrupt the vascular cells and the progression of periodontitis will also be determined.Read moreRead less