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.
Urinary tract infections are among the most common infectious diseases in humans, with approximately 40% of adult women having experienced at least one. I aim to characterise and compare the dynamics of the innate immune response in the urinary tract, in response to uropathogens and characterise bacterial factors affecting such responses. Understanding immune function provides important new understanding into these disease processes that may result in the development of new treatment approaches.
MOLECULAR ANALYSIS OF VIRULENCE FACTORS OF GROUP B STREPTOCOCCI
Funder
National Health and Medical Research Council
Funding Amount
$211,527.00
Summary
Streptococcus agalactiae, more commonly referred to as group B streptococcus (GBS), is the commonest cause of life-threatening infection (specifically bacteraemia, pneumonia and meningitis) in neonates. Mortality is high even in developed countries where antimicrobial therapy is readily available. In spite of the importance of GBS disease, the precise molecular mechanisms whereby the organism colonizes, invades and damages host tissues are poorly understood. The long term goal of this project is ....Streptococcus agalactiae, more commonly referred to as group B streptococcus (GBS), is the commonest cause of life-threatening infection (specifically bacteraemia, pneumonia and meningitis) in neonates. Mortality is high even in developed countries where antimicrobial therapy is readily available. In spite of the importance of GBS disease, the precise molecular mechanisms whereby the organism colonizes, invades and damages host tissues are poorly understood. The long term goal of this project is to gain a complete understanding of the pathogenesis of GBS disease and to apply this to development of improved preventative strategies. We propose to carry out a comprehensive molecular characterization of genes encoding putative GBS virulence determinants, with particular reference to those which encode the capacity to adhere to and invade host cells. GBS carrying defined mutations in these genes will be constructed and their virulence will be compared with that of the otherwise isogenic parental GBS. This will enable us to determine the precise contribution of each putative virulence factor to the pathogenesis of disease. Moreover, proteins shown to be important in this process will be tested for vaccine potential.Read moreRead less
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.
Targeting The Human Immune Response To Bacterial Superantigens.
Funder
National Health and Medical Research Council
Funding Amount
$165,424.00
Summary
This research investigates the human immune response to infection with toxin producing bacteria. Toxins activate the human immune system which can lead to serious illness or the development of disease that can progress rapidly and be associated with high rates of morbidity and mortality. Investigating the harmful effects of infection with toxin producing bacteria in humans and the damage caused by their toxins is essential for the development of effective therapeutic strategies.
Defining The Mechanism Of Invasive Disease Caused By Diverse Group A Streptococcal M Serotypes
Funder
National Health and Medical Research Council
Funding Amount
$393,061.00
Summary
Streptococcus pyogenes (group A Streptococcus; GAS) causes life-threatening invasive infections including flesh-eating disease and toxic shock syndrome (>600,000 cases and 163,000 deaths per year). We recently discovered the trigger for invasive disease in a globally disseminated GAS strain. The aim of this work is to determine whether this trigger applies to other strains associated with GAS invasive disease. These studies will allow the development of new therapeutics and treatments.