Molecular Characterization Of The Gingipains Of Porphyromonas Gingivalis
Funder
National Health and Medical Research Council
Funding Amount
$394,000.00
Summary
Chronic periodontitis is a bacteria-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 and has been associated with an increased risk of cardiovascular disease and pre-term birth and low birth weight. The bacterium Porphyromonas gingivalis has now been identified as a major pathogen in the development of chronic perio ....Chronic periodontitis is a bacteria-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 and has been associated with an increased risk of cardiovascular disease and pre-term birth and low birth weight. The bacterium Porphyromonas gingivalis has now been identified as a major pathogen in the development of chronic periodontitis. We have identified a major virulence factor of P. gingivalis which is an extracellular complex of proteins involved in binding and destroying host proteins. The aim of this proposal is to characterize the secretion, molecular processing and assembly of the cell surface complex using state-of-the-art proteomic techniques. This study will provide valuable insight into the molecular processes of a bacterial pathogen that leads to virulence. Detailed knowledge on the unique molecular events involved in secretion, processing and assembly of a major virulence factor will provide molecular targets for the development of specific inhibitors that may have utility as an adjunctive therapeutic and-or as part of a preventive regime or maintenance program for the control of chronic periodontitis. Further, the molecular insight that will result from this study will have broader application in the understanding of virulence factor processing of a Gram-negative pathogen that will provide paradigms for other bacterial pathogens.Read moreRead less
Novel Therapeutic Strategy Against Multidrug-resistant Gram-negative Bacteria
Funder
National Health and Medical Research Council
Funding Amount
$349,823.00
Summary
In the past two decades, there has been a marked decline in discovery and development of new antibiotics while there has been a remarkable increase in resistance to the currently available antibiotics. The growth in the number of resistant bacteria and lack of antibiotics available for treatment is very significant with gram-negative bacteria, such as Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia. Colistin, an old antibiotic that has been used little over the l ....In the past two decades, there has been a marked decline in discovery and development of new antibiotics while there has been a remarkable increase in resistance to the currently available antibiotics. The growth in the number of resistant bacteria and lack of antibiotics available for treatment is very significant with gram-negative bacteria, such as Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia. Colistin, an old antibiotic that has been used little over the last 40-50 years, has been 'taken off the shelf' and is now being used as a last line of defence to treat people with infections caused by these bacteria. Clearly, doctors and their infected patients will be in an even more precarious position than currently exists if resistance to colistin increases. We have discovered a novel therapeutic strategy that is able to reverse colistin resistance in P. aeruginosa. The studies proposed in this project will investigate this novel strategy across a range of multidrug-resistant bacteria and provide the information essential for rational use in patients. We propose that such a novel therapeutic strategy will provide a powerful weapon for the war on these 'superbugs'.Read moreRead less
Antibiotic Resistance And Multiple Antibiotic Resistance In Human Commensal Escherichia Coli In Australia
Funder
National Health and Medical Research Council
Funding Amount
$509,202.00
Summary
Antibiotic resistance, particularly resistance to all or nearly all of the antibiotics available for treatment is now very common and impacts heavily on the treatment of bacterial infections. This project will track resistance genes in reservoirs where antibiotic resistance genes may be present in high concentrations as these are a likely source of the resistance genes in disease-causing bacteria. One such reservoir, the bacteria in the intestines of healthy humans will be examined.
Targeting Polymyxin-resistant Gram-negative Superbugs: Development Of Novel Antimicrobial Lipopeptides
Funder
National Health and Medical Research Council
Funding Amount
$661,069.00
Summary
Prevalence of resistance to antibiotics among Gram-negative 'superbugs' is a major global medical challenge, which is highlighted by the Bad Bugs, No Drugs campaign of the Infectious Diseases Society of America. There are virtually no new antibiotics in the current drug development pipeline for these dangerous pathogens. In this project, novel lipopeptides will be designed, synthesised and evaluated against these 'superbugs'. Information obtained will be crucial for further drug development.
CD4+ T Cell-independent Immunity Against Salmonellae
Funder
National Health and Medical Research Council
Funding Amount
$550,226.00
Summary
Salmonella typhimurium is an important pathogen in both developed and developing countries where it causes significant HIV-linked morbidity. There is a pressing need to understand how immunity might be established against this organism that will function when the patient is immunocompromised either through age or through a comorbidity like HIV.
The Generation, Fate And Functional Potential Of Recent Thymic Emigrants
Funder
National Health and Medical Research Council
Funding Amount
$318,856.00
Summary
A particular kind of white blood cell, called a T lymphocyte, is responsible for controlling our immune responses to foreign invaders. These cells develop in the thymus, where they learn to distinguish between foreign invaders and self tissue, before emigrating to other organs. The regulation of this process is important to maintain a pool of T lymphocytes in the body. It is important that T lymphocytes do not respond against self tissue, as this can lead to a Oself destructO disease called auto ....A particular kind of white blood cell, called a T lymphocyte, is responsible for controlling our immune responses to foreign invaders. These cells develop in the thymus, where they learn to distinguish between foreign invaders and self tissue, before emigrating to other organs. The regulation of this process is important to maintain a pool of T lymphocytes in the body. It is important that T lymphocytes do not respond against self tissue, as this can lead to a Oself destructO disease called autoimmunity. Since these developing T lymphocytes will not see all kinds of self tissue while in the thymus, we propose that their education to prevent self-tissue reactivity may continue for some time after they leave the thymus.Read moreRead less