Zinc As An Antimicrobial Agent And Its Effect On The Pathogenesis Of Group A Streptococcus
Funder
National Health and Medical Research Council
Funding Amount
$352,359.00
Summary
This proposal focuses on Group A Streptococcus (GAS), a human pathogen estimated to cause 600,000 human deaths per year. We have shown that the host immune system uses zinc as an antibacterial agent and that GAS has processes that protect against zinc overload. We will determine the way in which zinc mobilization controls GAS infection and how GAS responds to to an increase in zinc concentration. The results will provide new insights into zinc’s role in protection against bacterial infections.
Interaction Of Group A Streptococci With Intracellular Innate Immune Defence
Funder
National Health and Medical Research Council
Funding Amount
$824,252.00
Summary
The pathogenic bacterium group A streptococcus (GAS) is estimated to cause ~700 million cases of self-limited throat or skin infection each year worldwide. GAS infections result in over 600,000 human deaths. This disease burden places GAS in the “top 10” causes of human infectious disease deaths worldwide. We have discovered a hitherto unknown mechanism by which GAS subvert the human immune system. An improved understanding of this mechanism will lead to novel ways to combat GAS infections.
Characterising The Role Of Streptokinase Polymorphism In Invasive Pathogenesis Of Streptococcus Pyogenes.
Funder
National Health and Medical Research Council
Funding Amount
$480,535.00
Summary
Invasive bacterial pathogens such as Streptococcus pyogenes, can hijack host proteins and use them to facilitate the disease process. S. pyogenes secrete streptokinase to activate a host protease (plasminogen) which is used by the bacterium to invade through host tissue. This project will characterise the molecular mechanisms involved in streptokinase mediated activation of plasminogen which will assist the generation of novel therapeutics to treat invasive diseases.
Worldwide Molecular Analysis Of Streptococcus Pyogenes Scarlet Fever Outbreaks
Funder
National Health and Medical Research Council
Funding Amount
$544,041.00
Summary
The microorganism group A Streptococcus (also called GAS or Streptococcus pyogenes) ranks among the top 10 infectious disease killers of humans. Recently, outbreaks of scarlet fever have occurred in both Asia and the United Kingdom, placing a serious strain on health systems. The reasons underlying these outbreaks remain unknown. Our team will lead the global effort to characterise this rise in scarlet fever, and provide recommendations and solutions to health professionals.
Public Health Interventions For The Control Of Group A Streptococcal Disease And Scabies In Endemic Populations
Funder
National Health and Medical Research Council
Funding Amount
$470,144.00
Summary
The bacterium Group A Streptococcus (GAS) is an important cause of morbidity and mortality globally. The skin infestation scabies is an important portal of entry for GAS because it predisposes to skin sores. I propose to develop two research programs aimed at controlling these diseases: one is development of GAS vaccines and the other is investigating population-based interventions for control of scabies and related GAS skin infection.
The Efficacy Of Mass Drug Administration Strategies To Control Scabies In A Highly Endemic Population.
Funder
National Health and Medical Research Council
Funding Amount
$705,396.00
Summary
Globally there are an estimated 300 million scabies cases annually. Many Pacific countries, including Fiji, have among the highest rates in the world. This island based study in Fiji will compare the short and long term efficacy of two mass treatment protocols using oral ivermectin or topical permethrin against conventional treatment. This study will be the first population-wide treatment trial for scabies that compares new interventions to standard of care treatment.
Role Of Streptococcus Agalactiae Glyceraldehyde 3-phosphate Dehydrogenase (GAPDH) In Infection And Potential As A Target To Control Colonization In The Female Genital Tract
Funder
National Health and Medical Research Council
Funding Amount
$677,177.00
Summary
Extracellular proteins produced by pathogenic bacteria can facilitate microbial colonization of the host by mediating binding to host cells and by modulating the immune system. These proteins exert their effects by subverting specific elements of the immune system and this can allow infection to worsen. This project will increase our understanding of how this bacterium chronically colonizes humans and will identify the potential of a bacterial protein, termed GAPDH, as a target for control.
Tropical Diseases: Translating Discoveries Into Better Health
Funder
National Health and Medical Research Council
Funding Amount
$19,803,660.00
Summary
Major progress being made in control of many infectious diseases occurring in tropical areas, including malaria worms and the bacteria that causes strep throat. However, currently available tools will not permit their full control or elimination. This program is aimed to improve understanding of these diseases and to develop the much needed tools that will be required for their elimination.
Activation And Inhibition Of The Plasminogen/Plasmin System
Funder
National Health and Medical Research Council
Funding Amount
$800,663.00
Summary
Plasmin is crucial enzyme present in blood plasma that functions in clot dissolution, inflammation, tissue remodeling, and wound healing. We aim to study how this enzyme system is controlled, by studying its interaction with receptors, co-factors and inhibitors. The information we gain will help drive the development of new generation therapeutics for the fine control of plasmin function in clotting disease, bleeding and inflammation.
Preclinical Studies Of Group A Streptococcal Vaccine Candidates
Funder
National Health and Medical Research Council
Funding Amount
$532,492.00
Summary
Group A streptococcus causes 520,000 deaths each year. A safe and effective vaccine is not commercially available. We have identified 2 new protective candidate antigens, and we seek to undertake critical preclinical studies to provide further proof-of-concept data. This work will underpin commercial decisions by our industry partner (Wyeth) leading to human trials and the development of a safe group A streptococcal vaccine for human use.