Identification Of Porphyromonas Gingivalis Genes Required For Iron/haem Acquisition And Biofilm Formation
Funder
National Health and Medical Research Council
Funding Amount
$476,836.00
Summary
Periodontal diseases are some of the most common bacterial diseases of humans and along with dental caries, account for approximately 90% of all tooth loss in the Australian population. A recent survey of oral health in Australia found that in the 30-34 age group over 20% of people had moderate to severe periodontal disease, indicating that periodontitis is a major public health problem. Specific bacteria, especially Porphyromonas gingivalis, that grow as bacterial biofilms (dental plaque) cause ....Periodontal diseases are some of the most common bacterial diseases of humans and along with dental caries, account for approximately 90% of all tooth loss in the Australian population. A recent survey of oral health in Australia found that in the 30-34 age group over 20% of people had moderate to severe periodontal disease, indicating that periodontitis is a major public health problem. Specific bacteria, especially Porphyromonas gingivalis, that grow as bacterial biofilms (dental plaque) cause periodontal disease. In this study we will utilise the latest technology available to determine which genes of the bacterium are important for biofilm growth, iron acquisition and virulence in an animal model. We will investigate how the bacterium acquires iron, as there is usually little available iron for bacterial growth on human tissues and the ability of the bacterium to free itself from this iron limitation is associated with pathogenicity. The determination of the role of iron availability in biofilm formation and virulence of the bacterium will help us to understand the changes that occur in the initiation of disease and may allow the development of early intervention strategies. The significance of this work is that we will gain an understanding of how this bacterium functions as an opportunistic human pathogen. We will determine which genes are essential for growth as a biofilm and to produce disease in an animal model. This will enable the development of therapeutic and prophylactic interventions targeted to specific bacterial gene products required to produce disease.Read moreRead less
Characterization Of A Novel Secretion System Necessary For Porphyromonas Gingivalis Virulence.
Funder
National Health and Medical Research Council
Funding Amount
$596,412.00
Summary
In this study we will characterize a novel bacterial secretion system that we have discovered. This sytem mediates the secretion of proteins from the bacterial cell and their attachment to the cell surface. This system is essential for the virulence of Porphyromonas gingivalis, a bacterium associated with chronic periodontitis. The chacterization of this system may offer opportunities for the development of new treatments to target this disease.
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