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.
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.
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.
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.
Defining The Role Of Zinc At The Host-pneumococcal Interface
Funder
National Health and Medical Research Council
Funding Amount
$870,925.00
Summary
Streptococcus pneumoniae is the world’s foremost bacterial pathogen. In Australia, bacterial infections are responsible for more than 9000 deaths every year, and the economic burden associated with treating diseases arising from pneumococcal infections is more than $1 billion annually. This proposal aims to define the role of the transition metal zinc in innate immune resistance to bacterial infection. This knowledge will reveal new targets for next generation antimicrobial therapeutics.
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.
Optimising Intervention Strategies To Reduce The Burden Of Group A Streptococcus In Aboriginal Communities
Funder
National Health and Medical Research Council
Funding Amount
$856,896.00
Summary
Skin sores are highly prevalent in remote Australian Indigenous communities and can lead to invasive infections and rheumatic heart disease. We will develop mathematical models to understand the transmission of skin sores, allowing us to define the optimal extent (household, community, region), timing and triggers for interventions to interrupt transmission. This will guide public health policy in reducing the prevalence of skin sores and scabies, and their accompanying disease burden.
Integrated Bacterial Genomics And Virulence Analysis Of Uropathogenic Streptococcus Agalactiae
Funder
National Health and Medical Research Council
Funding Amount
$747,457.00
Summary
Urinary tract infections (UTI), which start as a bladder infection and often evolve to encompass the kidneys, are among the most common infectious diseases in humans. Streptococcus agalactiae is an important cause of gram-positive bacterial UTI. We will study the genomes and functions of specific genes in reference strains of this bacterium isolated from patients with different forms of infection to elucidate how bacterial genes and virulence factors contribute to these types of infections.
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.
Group A Streptococcal Human Challenge Study: Accelerating Vaccine Development
Funder
National Health and Medical Research Council
Funding Amount
$2,018,741.00
Summary
Infection with group A streptococcus (GAS) is a major cause of morbidity and mortality worldwide, including in the Aboriginal population of Australia. Concerted efforts for vaccine development have been hampered by the absence of a suitable animal model. To address this critical knowledge gap we propose to develop a controlled human infection model of GAS infection. This model will provide a direct pathway for the future appraisal of novel GAS vaccines.