A Dual Antigen Synthetic Peptide Subunit Vaccine Approach To Prevent Streptococcal Associated Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$604,017.00
Summary
Infection with streptococcus is responsible for causing more than 500,000 deaths each year, the majority of which are due to rheumatic fever and rheumatic heart disease, which contributes to cardiovascular disease. Our research is aimed at the development of a vaccine to prevent heart disease and involves targeting multiple molecules present on the bacterial surface. We will use a novel vaccine delivery system developed in the laboratory, which will enable the vaccine to be delivered nasally.
Optimising Interventions For Staphylococcus Aureus And Skin Infections
Funder
National Health and Medical Research Council
Funding Amount
$338,381.00
Summary
Staphylococcal and streptococcal infections are major causes of illness and death, particularly in Indigenous Australians. These include invasive bloodstream infections and skin infections that lead to chronic kidney and heart disease. I will conduct clinical trials to optimise the management of staphylococcal bloodstream infections using novel trial methods, and use genomics and mathematical modelling to understand and reduce the burden of skin infections in Indigenous communities.
Modelling Streptococcal Urogenital Tract Infection To Study Mechanisms Of Bacterial Colonization And Persistence
Funder
National Health and Medical Research Council
Funding Amount
$412,085.00
Summary
Colonization of the urogenital tract with bacterial pathogens is one of the most common infections in humans. In Australia millions of people are colonized in their urogenital tracts at any given time, often asymptomatically, and many such individuals require medical intervention for the treatment of consequent infections that result from persistent colonization. Bacterial colonization of the urogenital tract is associated with a variety of disease presentations including urinary tract infection ....Colonization of the urogenital tract with bacterial pathogens is one of the most common infections in humans. In Australia millions of people are colonized in their urogenital tracts at any given time, often asymptomatically, and many such individuals require medical intervention for the treatment of consequent infections that result from persistent colonization. Bacterial colonization of the urogenital tract is associated with a variety of disease presentations including urinary tract infections and neonatal infections resulting from vertical transmission of colonizing bacteria from mothers to newborns. Aside from sexually-transmitted diseases the most prominent bacterial pathogens that colonize the urogenital tract are Group B Streptococcus (GBS) and Escherichia coli. GBS in particular exist in the female urogenital tract as a persistent microbial reservoir in up to 40% of pregnant women and are transmitted to newborns in up to 72% of live births. Colonization of newborns leads to invasive disease including pneumonia, sepsis, and meningitis. While the disease presentations resulting from colonization of the urogenital tract vary the underlying basis that leads to disease is antecedent bacterial persistence in the urogenital tract despite immune system activation. The mechanisms whereby GBS evade immune responses in the urogenital tract to allow their survival are unknown. I will define the immune-evasion mechanisms and virulence traits used by GBS, as a model urogenital pathogen, to successfully colonize the urogenital tract in the face of mounting immune responses. These studies will provide a better understanding of the pathogenesis of urogenital disease in terms of bacterial colonization and immune-evasion strategies. This will shed light onto new approaches for the prevention and treatment of urogenital disease in humans such as improved vaccination, locally acting cytokines, and deliberate colonization with non-invasive strains for the prevention of disease.Read moreRead less
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.
Blood Group Antigen Recognition By Group A Streptococcus Mediates Host Colonisation
Funder
National Health and Medical Research Council
Funding Amount
$470,821.00
Summary
Group A streptococcus (GAS) is responsible for approximately 700 million cases of localised infection and 600,000 cases of invasive infection globally each year. Certain bacteria have been shown to recognise sugars (known as glycans) on host cells. This project will look at how GAS use sugars at the surface of host cells to initiate disease, and determine if differences in the types of sugars present on host cells alter the ability of GAS to initiate infection.
Do Rapid Detection & Isolation Of Colonised Patients Reduce MRSA Spread? An Epidemiological, Economic & Modelling Study
Funder
National Health and Medical Research Council
Funding Amount
$354,299.00
Summary
Methicillin-resistant Staphylococcus aureus (MRSA) is the antibiotic resistant form of Golden Staph. It is one of the most common causes of hospital acquired infection. Despite the presence of MRSA for more than 40 years in our hospitals, the most efficient ways of controlling it are still debated. Some experts recommend swabbing all high risk patients for MRSA, isolating those found to be carriers it in single rooms or with other carriers and using special precautions, such as gowns and gloves, ....Methicillin-resistant Staphylococcus aureus (MRSA) is the antibiotic resistant form of Golden Staph. It is one of the most common causes of hospital acquired infection. Despite the presence of MRSA for more than 40 years in our hospitals, the most efficient ways of controlling it are still debated. Some experts recommend swabbing all high risk patients for MRSA, isolating those found to be carriers it in single rooms or with other carriers and using special precautions, such as gowns and gloves, when in contact with these patients. One of the problems with this approach is that it takes 2-3 days to detect MRSA from swabs using the usual culture methods in the microbiology laboratory. This means that there are delays in instituting control measures, which may reduce their effectiveness. We plan to test whether use of isolation and special precautions is better than our current practices in preventing the spread of MRSA from patient to patient in the Royal Melbourne Hospital intensive care unit. Patients will be swabbed several times during their admission to see if they are carrying MRSA. We will use new, rapid laboratory methods that can detect MRSA within hours from these patient specimens. This will mean that if patients are found to be carriers, isolation and special precautions can be implemented early. We will compare how many people get MRSA in the time when we are not using any special precautions with how many get it in the time when we are. We are also going to undertake an economic analysis to see whether, even if these new diagnostic methods are more expensive that standard methods, they may still be worth the cost if we can prevent infections in patients. This study will help infection control practitioners to decide whether patients should be isolated with special precautions if they are MRSA carriers. The results of this study will contribute to better patient outcomes, lower hospital costs and more efficient use of resources.Read moreRead less
Characterising The Molecular Pathogenesis Of Newly Emergent Invasive Group A Streptococcus M4 Serotypes In Australia
Funder
National Health and Medical Research Council
Funding Amount
$523,756.00
Summary
Group A Streptococcus (GAS) is a human pathogen of global significance, responsible for life-threatening invasive infections such as flesh-eating disease (>650,000 cases per year), with a mortality rate of 25%. A recent outbreak of serotype M4 GAS caused severe invasive infections in Queensland Australia. The aim of this work is to determine how M4 GAS causes invasive disease. Understanding this mechanism will allow the development of new generation therapeutics, treatments and improved healt ....Group A Streptococcus (GAS) is a human pathogen of global significance, responsible for life-threatening invasive infections such as flesh-eating disease (>650,000 cases per year), with a mortality rate of 25%. A recent outbreak of serotype M4 GAS caused severe invasive infections in Queensland Australia. The aim of this work is to determine how M4 GAS causes invasive disease. Understanding this mechanism will allow the development of new generation therapeutics, treatments and improved health outcomes.Read moreRead less