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.
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
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
Unified Model For Group A Streptococcal Invasive Disease Initiation.
Funder
National Health and Medical Research Council
Funding Amount
$605,221.00
Summary
Streptococcus pyogenes (group A streptococcus; GAS) is a bacterium that causes human skin and throat infections as well as highly invasive diseases including necrotising fasciitis and streptococcal toxic shock-like syndrome. We have recently discovered the trigger mechanism for GAS invasive disease. We hypothesise that the initial host response at the site of infection selects for a GAS invasive phenotype. We propose to examine the chain of events which result in tissue invasion in order to unde ....Streptococcus pyogenes (group A streptococcus; GAS) is a bacterium that causes human skin and throat infections as well as highly invasive diseases including necrotising fasciitis and streptococcal toxic shock-like syndrome. We have recently discovered the trigger mechanism for GAS invasive disease. We hypothesise that the initial host response at the site of infection selects for a GAS invasive phenotype. We propose to examine the chain of events which result in tissue invasion in order to understand these disease processes and allow the development of future therapeutic interventions.Read moreRead less
Role Of Bacteriophage-encoded Streptodornase In Invasive Disease Caused By Diverse Group A Streptococcal M Serotypes.
Funder
National Health and Medical Research Council
Funding Amount
$832,544.00
Summary
Streptococcus pyogenes (group A streptococcus, GAS) is estimated to cause ~700 million cases of self-limited throat or skin infection each year worldwide. Invasive GAS disease occurs in approximately 1-1000 cases, with associated mortality of 25%. We have recently discovered that a viral infection can reprogram GAS for invasive disease propensity. We will investigate whether this phenomenon is widespread, in order to understand this process and develop future therapeutics.
Antibiotic resistance increases mortality and costs in the Intensive Care Unit (ICU), but the impact of antibiotic therapy has not been adequately studied. We propose to characterise the behaviour of key elements of the bacterial microflora (resistant bacteria and major resistance genes) in response to antibiotics. We have developed new rapid diagnostics to harness these data and this proposal has the potential to greatly improve diagnostic speed and accuracy and thus clinical outcomes.
Structural Investigations Of Bacterial Evasion Of IgA Mucosal And Systemic Immunity
Funder
National Health and Medical Research Council
Funding Amount
$488,812.00
Summary
Nose, throat and skin infections are often caused by streptococcal and staphylococcal bacteria, known as Strep Throat and Golden Staph. Infections can be life-threatening in newborns, the elderly or individuals with weak immune systems. These bacteria make proteins bind and inactivate immune proteins. Our research examines the structural basis for bacterial interactions with a key immune system protein (an antibody called IgA) and may lead to new prevention and treatment strategies.
Identifying The Physiological Conditions That Promote Lateral Gene Transfer And Evolution Of New Streptococcal Pathovars
Funder
National Health and Medical Research Council
Funding Amount
$415,907.00
Summary
In the last few decades, the diseases caused by the three human pathogens, groups A, B and G streptococcus have undergone a transformation. The exchange of DNA between these species is speculated to play a role in this changing disease association. In this proposal we will identify the specific physiological and growth conditions that promote DNA transfer. Such information may help in our understanding of how new pathogenic strains of streptococci arise.
Investigation Of The Localisation, Transport And Vaccine Potential Of Group A Streptococcal Cell Surface Proteins.
Funder
National Health and Medical Research Council
Funding Amount
$505,523.00
Summary
Streptococcus pyogenes (group A streptococcus; GAS) is a bacterium that causes human skin and throat infections as well as highly invasive diseases including necrotising fasciitis. Additionally, serious sequeale, including rheumatic fever and acute glomerulonephritis, may result following repeated infection. We have recently examined the GAS cell wall and identified 23 proteins that are surface exposed, 20 of which are novel. We hypothesise that a number of these surface exposed proteins represe ....Streptococcus pyogenes (group A streptococcus; GAS) is a bacterium that causes human skin and throat infections as well as highly invasive diseases including necrotising fasciitis. Additionally, serious sequeale, including rheumatic fever and acute glomerulonephritis, may result following repeated infection. We have recently examined the GAS cell wall and identified 23 proteins that are surface exposed, 20 of which are novel. We hypothesise that a number of these surface exposed proteins represent candidate vaccine antigens capable of conferring protective immunity. We therefore propose to examine these surface proteins as components of experimental vaccines against GAS.Read moreRead less