Characterization Of The Type IX Secretion System In Porphyromonas Gingivalis
Funder
National Health and Medical Research Council
Funding Amount
$831,656.00
Summary
Periodontitis is associated with the keystone pathogen Porphyromonas gingivalis. We have identified a novel protein secretion machine comprised of at least 12 components in P. gingivalis which transports the bacterium's major virulence factors to the cell surface and attaches them to the outer membrane. We aim to determine the spatial arrangement and specific role of each of these 12 components and thereby provide targets for future treatments against this disease.
The RgpA-Kgp Proteinase-adhesin Complex And Virulence Of Porphyromonas Gingivalis
Funder
National Health and Medical Research Council
Funding Amount
$527,310.00
Summary
Periodontitis is a bacterial-associated inflammatory disease of the supporting tissues of the teeth which can result in tooth loss. The disease is a major public health problem with a large economic burden. A bacterium Porphyromonas gingivalis has now been identified as a major causative agent of chronic periodontitis. We have identified a major virulence factor of P. gingivalis. This virulence factor is a complex of proteins, encoded by two genes, and is involved in binding and destruction of h ....Periodontitis is a bacterial-associated inflammatory disease of the supporting tissues of the teeth which can result in tooth loss. The disease is a major public health problem with a large economic burden. A bacterium Porphyromonas gingivalis has now been identified as a major causative agent of chronic periodontitis. We have identified a major virulence factor of P. gingivalis. This virulence factor is a complex of proteins, encoded by two genes, and is involved in binding and destruction of host tissue. When used as a vaccine in animal models the protein complex protects against P. gingivalis infection. Animal protective sera recognises a segment of the protein complex involved in binding to host substrates. The aim of this project is to continue this work on the characterisation of this complex and its role in virulence in an approach to ultimately develop a defined vaccine against P. gingivalis based on this protein complex, in particular the sequences involved in binding. The expected outcome of this research is the further biochemical characterisation of the RgpA-Kgp protein complex and its role in virulence as well as development of a defined vaccine prepared using recombinant DNA and chemical synthesis techniques that protects against P. gingivalis infection in animal models of disease.Read moreRead less
Allostatic Mediators Of Socioeconomic Inequalities In Periodontitis Among Australian Adults
Funder
National Health and Medical Research Council
Funding Amount
$368,000.00
Summary
Periodontal (gum) disease is a significant cause of tooth loss among adults in Australia. Bacteria (germs) that stick to teeth in dental plaque are the primary cause of gum disease. However, the amount of damage caused to the gums depends heavily on the body's immune system which fights infection throughout the body. Like many other health conditions, gum disease occurs at a higher rate in people in a relatively low socioeconomic-position (SEP) compared to people from high SEP. Studies of other ....Periodontal (gum) disease is a significant cause of tooth loss among adults in Australia. Bacteria (germs) that stick to teeth in dental plaque are the primary cause of gum disease. However, the amount of damage caused to the gums depends heavily on the body's immune system which fights infection throughout the body. Like many other health conditions, gum disease occurs at a higher rate in people in a relatively low socioeconomic-position (SEP) compared to people from high SEP. Studies of other health conditions have shown that psychosocial stress (eg. job strain, financial stress) disproportionately affects people in low SEP groups. Stress, in turn, is known to alter the body's defense mechanisms, including the immune system, contributing to higher rates of conditions such as heart disease. Researchers have used the term allostatic load to describe this failure of the body's defense system under stress. Stress has also been suggested as a contributing factor in gum disease. This study will investigate whether this sequence of events producing allostatic load also plays a role in gum disease. We will study a random sample of 610 Australian adults from the full range of SEP backgrounds. We will ask them about their experience of daily stress, and measure their levels of gum disease and dental plaque. We will also collect samples of fluid from around their gums to measure quantities of two chemicals that indicate the activity of immune defense mechanisms in the gums. We will analyze these results to determine whether stress affects the body's responses to dental plaque, and whether that response accounts for differences in levels of gum disease between SEP groups. Results from this study will pinpoint the role of common bodily defense mechanisms in the development of gum disease. These results may help to identify sources of stress that, if controlled, could reduce rates of gum disease and other conditions affected by allostatic load.Read moreRead less
Relationship Between Periodontal Disease And Rheumatoid Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$520,657.00
Summary
Periodontal (gum) disease and rheumatoid arthritis are two of the most common chronic inflammatory diseases affecting humans. These two diseases have remarkably similar patterns of tissue destruction. It is possible that individuals with chronic periodontitis may prime or predispose individuals prone to developing rheumatoid arthritis. Treatment of periodontal disease may help reduce the severity of rheumatoid arthritis.
Iron/hemin Transport Systems Of Porphyromonas Gingivalis
Funder
National Health and Medical Research Council
Funding Amount
$392,036.00
Summary
Periodontitis is a bacterial-associated disease of the supporting structures of the teeth and can result in tooth loss. The disease is classified as a major public health problem with an enormous economic burden. A bacterium, Porphyromonas gingivalis, has now been implicated as a major causative agent of periodontitis in adults. To survive and grow within humans pathogenic bacteria must be able to acquire essential elements, including iron. The human host has developed a variety of mechanisms to ....Periodontitis is a bacterial-associated disease of the supporting structures of the teeth and can result in tooth loss. The disease is classified as a major public health problem with an enormous economic burden. A bacterium, Porphyromonas gingivalis, has now been implicated as a major causative agent of periodontitis in adults. To survive and grow within humans pathogenic bacteria must be able to acquire essential elements, including iron. The human host has developed a variety of mechanisms to restrict the amount of iron available as a means of limiting the growth of bacterial pathogens. In response to this iron limitation Porphyromonas gingivalis has developed novel ways of obtaining this essential element. We have identified a novel iron transport system that P. gingivalis uses to obtain iron from the human host. A component of this transport system, FetB is a surface protein antigen. The aims of this project are to: i. Determine the mechanism by which this novel iron transport system functions by genetic manipulation of the organism using molecular biology techniques. ii. Determine how important this transport system is for the pathogenicity of the bacterium. iii. Prepare the FetB protein using recombinant DNA technology. iv. Test the recombinant FetB protein and another iron transport protein (Tlr) in animal models to determine their efficacy as a vaccine for periodontitis. The expected outcomes of this research are:- i. the understanding of how P. gingivalis transports iron. ii. an understanding of the importance of iron transport systems to the pathogenicity of the bacterium. iii. a P. gingivalis vaccine with efficacy in animals based on an iron transport protein(s).Read moreRead less
Cell Surface Protein Antigens Of Porphyromonas Gingivalis
Funder
National Health and Medical Research Council
Funding Amount
$339,634.00
Summary
Periodontitis is a bacterial-associated disease of the supporting structures of the teeth and can result in tooth loss. The disease is classified as a major public health problem with an enormous economic burden. A bacterium Porphyromonas gingivalis has now been identified as a major causative agent of periodontitis in adults. We have developed methods to rapidly identify all the surface protein antigens of P. gingivalis using mass spectrometry and then using recombinant DNA technology to expres ....Periodontitis is a bacterial-associated disease of the supporting structures of the teeth and can result in tooth loss. The disease is classified as a major public health problem with an enormous economic burden. A bacterium Porphyromonas gingivalis has now been identified as a major causative agent of periodontitis in adults. We have developed methods to rapidly identify all the surface protein antigens of P. gingivalis using mass spectrometry and then using recombinant DNA technology to express these recombinant antigens for testing in animal models of disease. The aim of this project is: (i) to rapidly identify cell surface protein antigens of P. gingivalis using novel techniques. (ii) prepare these antigens using recombinant DNA technology. (iii) use patient and healthy subject sera as well as animal antisera to screen the recombinant antigens for suitable candidates for an immunodiagnostic product and-or vaccine. (iv) test the recombinant antigens in animal models of disease in an approach to identify a candidate antigen for a vaccine. The expected outcomes of this research are that (i) we will develop techniques that can be used to characterise the cell surface antigens of any pathogenic bacterium. (ii) we will determine the organisation and the structure of the cell surface proteins of P. gingivalis. (iii) we will identify an abundant, unique and immunogenic protein of the P. gingivalis surface that will be a suitable candidate antigen for the development of a sensitive and specific immunodiagnostic. (iv) we will identify a cell surface antigen that when used as a vaccine in animals prevents disease caused by P. gingivalis.Read moreRead less
A Multi-protein Vaccine Targeting The Oral Pathogens Associated With Chronic Periodontitis
Funder
National Health and Medical Research Council
Funding Amount
$717,692.00
Summary
Periodontitis is a chronic inflammatory disease associated with specific bacteria leading to the destruction of the toothÍs supporting tissues and ultimately tooth loss and is a major public health problem in all societies. Our research is focused on designing a vaccine that targets the major bacteria associated with periodontitis. We aim to produce a triple antigen vaccine and investigate the applicability of a vaccine administered under the tongue as an alternative to needle injections.
The Bacterial Type IX Secretion System In Polymicrobial Dysbiosis And Chronic Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$1,900,000.00
Summary
Periodontitis (severe gum disease) affects 1 in 3 adults and has been linked with heart attacks, cancer and dementia. I will lead a multidisciplinary team investigating the interaction between disease causing bacteria in the mouth and the immune response which results in destruction of the tooth’s supporting tissues and allows bacteria to enter the blood stream. The expected outcome is the development of a novel therapy which will stop progression of disease associated with these pathogens.