Molecular Basis For The Emergence Of Community Acquired Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$427,518.00
Summary
Golden Staph is a major problem in our hospitals but serious Golden Staph infections are increasingly common in the community, among otherwise healthy people who have had no contact with hospitals. This project will find out how Golden Staph is evolving to become more likely to cause disease in the community. This knowledge can then be used to design new strategies for early detection, prevention and treatment.
Helicobacter Pylori VacA Toxin: Modulation Of Human Mitochondrial Function By A Bacterial Pathogen
Funder
National Health and Medical Research Council
Funding Amount
$508,003.00
Summary
This work will greatly further our understanding of how a bacterium, Helicobacter pylori, causes stomach ulcers and cancer. We will use cutting edge model systems to study the VacA toxin that is secreted from the bacteria and is targeted to human cells. We will examine where the toxin goes and how it affects our cells. It is expected that the improved understanding that will arise from this work will assist researchers to better devise drugs against this prevalent pathogen.
Zinc: The Molecular Basis Of It�s Toxicity To Gram-positive Pathogens And It�s Exploitation By The Innate Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$588,398.00
Summary
Zinc in excess is toxic to bacteria, and the release of zinc is an important part of the immune response. Dietary zinc deficiency leads to increased susceptibility to pathogenic bacteria. How zinc affords protection has remained a mystery. We have identified a novel mechanism in 2 priority human pathogens by which zinc competes for the essential metal ion manganese. We will elucidate the molecular details of this mechanism and how it is harnessed by the immune system.
Environmental Regulation Of Virulence In Attaching And Effacing Enterobacteria
Funder
National Health and Medical Research Council
Funding Amount
$569,063.00
Summary
Disease-causing bacteria must respond to the extreme conditions, such as acid and bile, which they encounter in their hosts. They achieve this by sensing their environment and activating genes that enhance their survival and ability to cause disease. In this project we will define the mechanisms by which these sensing and response pathways occur, using E. coli as a model. The information obtained from this research should lead to new strategies to treat and prevent bacterial infections.
Characterisation Of A Newly-discovered, Virulence-associated, Protein Secretion System Of Enteropathogenic E. Coli
Funder
National Health and Medical Research Council
Funding Amount
$582,149.00
Summary
The cell walls of bacteria act as a barrier to the export of any proteins they produce. We recently discovered a protein secretion system, which diarrhoea-causing strains of E. coli require to cause disease. The aim of this study is to characterise this secretory system, and discover how it functions and what it secretes. The knowledge obtained from this research will shed new light on how E. coli causes disease and could reveal novel methods to treat and prevent infections with this bacterium.
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
Novel Compounds For Use As Inhibitors Of Virulence Of Human Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$220,500.00
Summary
There is growing concern over the emergence of multi-drug resistant strains of bacteria which are no longer treatable with the current generation of antibiotics. This highlights the urgent need for development of the next generation of therapeutic agents to supplement or replace the current antibiotics. Our research team has identified a class of compounds which are naturally produced by a marine alga that may be effective in the control of bacterial pathogens. These compounds work by interferin ....There is growing concern over the emergence of multi-drug resistant strains of bacteria which are no longer treatable with the current generation of antibiotics. This highlights the urgent need for development of the next generation of therapeutic agents to supplement or replace the current antibiotics. Our research team has identified a class of compounds which are naturally produced by a marine alga that may be effective in the control of bacterial pathogens. These compounds work by interfering with the way many pathogens regulate the production of virulence traits. Some bacteria are able to signal members of their population by the specific uptake and recognition, through a receptor protein, of chemical cues they secrete into the environment. Accumulation of these cues or signals triggers expression of the genes that code for the virulence traits. Moreover, one particular class of these signal response proteins has been identified in many pathogens and has been shown to regulate protease production and production of a protective extracellular slime layer called a capsule. If one or more of these traits can be blocked, then the virulence of the bacterium can be reduced. We have preliminary data which demonstrates that the algal compounds do in fact prevent the expression of virulence traits and thus should be useful as new agents for the treatment of disease. The causative agents of cholera and severe gatroenteritis, Vibrio cholerae and V. parahaemolyticus respectively, have one or the other of these virulence traits, but the pathogen Vibrio vulnificus has all three and therefore is an excellent model pathogen. We propose to explore the ability of the algal compounds to specifically shut down expression of virulence factors with a long term aim for the development of these compounds as novel antimicrobial therapies for the post-antibiotic era.Read moreRead less