Regulation Of Porphyromonas Gingivalis Gene Expression
Funder
National Health and Medical Research Council
Funding Amount
$531,696.00
Summary
Chronic periodontitis (gum disease) is a chronic inflammatory disease of the supporting tissues of the teeth associated with bacteria that results in the destruction of tooth support and can ultimately lead to tooth loss. The disease is a major public health problem with a large economic burden and has been associated with an increased risk of cardiovascular disease. The bacterium Porphyromonas gingivalis is recognized as the major causative pathogen in the development of chronic periodontitis. ....Chronic periodontitis (gum disease) is a chronic inflammatory disease of the supporting tissues of the teeth associated with bacteria that results in the destruction of tooth support and can ultimately lead to tooth loss. The disease is a major public health problem with a large economic burden and has been associated with an increased risk of cardiovascular disease. The bacterium Porphyromonas gingivalis is recognized as the major causative pathogen in the development of chronic periodontitis. This bacterium is part of subgingival dental plaque, a biofilm attached to the surface of the tooth below the gum line, and releases a range of proteins and cytotoxic agents that cause damage to the tooth's supporting tissues both directly and indirectly through the dysregulation of the host's immune response. To cause disease this bacterium must be able to grow as a biofilm and withstand the immune response of the host. Detailed knowledge of how this bacterium is able to establish and proliferate in subgingival plaque, tolerate the oxidative attack and elevated temperatures that are part of the immune response and obtain the essential micronutrient iron will provide new targets for the development of specific inhibitors that may have utility as an adjunctive therapeutic for the control of chronic periodontitis. We will use a state of the art DNA microarray analysis to determine the proteins that regulate genes associated with the virulence of this bacterium. The insights we gain from this study will have broader application for the understanding of human disease that is caused by bacteria that grow as biofilms on various surfaces of the human body.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