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.
Virulence And Oxidative Stress In Streptococcus Pneumoniae
Funder
National Health and Medical Research Council
Funding Amount
$110,125.00
Summary
Streptococcus pneumoniae is an important human pathogen that causes pneumonia, meningitis and bacteraemia as well as otitis media in young children. It is a cause of high morbidity and mortality around the world. S. pneumoniae grows by fermentative metabolism, a characteristic of anaerobic organisms, but it is able to adapt towards oxygen in the environment. This adaptive ability enables S. pneumoniae to live under conditions of high oxygen tension (eg. the upper respiratory tract) or under almo ....Streptococcus pneumoniae is an important human pathogen that causes pneumonia, meningitis and bacteraemia as well as otitis media in young children. It is a cause of high morbidity and mortality around the world. S. pneumoniae grows by fermentative metabolism, a characteristic of anaerobic organisms, but it is able to adapt towards oxygen in the environment. This adaptive ability enables S. pneumoniae to live under conditions of high oxygen tension (eg. the upper respiratory tract) or under almost anaerobic conditions (eg. the middle ear) in the human body. The emergence of antibiotic resistant pneumococci and limitations of current vaccines has led to increased interest in understanding the molecular mechanisms of pathogenesis of this bacterium. Of particular interest has been the pneumococcal surface antigen PsaA, which has been shown to be a protective immunogen in mice. It has also been shown that psaA mutants exhibit massively reduced virulence in mice in intranasal and intraperitoneal challenge models. Taken together, these data have led to the suggestion that PsaA might be an effective vaccine antigen or antimicrobial target. We postulate that PsaA is involved in the oxidative stress response and virulence under aerobic conditions and have devised a study to determine the procise role of this protein in disease caused by Streptococcus pneumoniae.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
Regulation Of Pulmonary Immune Responses To Subunit Vaccines Against Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$509,202.00
Summary
Tuberculosis (TB) remains an enormous health problem world-wide. Improving the effectiveness of anti-TB vaccines is essential for its control. The first approach to improving subunit TB vaccines will be to manipulate the cellular immune response to the vaccine by increasing the positive cytokine signals, or reducing inhibitory effects on the immune response. The second approach is to develop new subunit vaccines to deliver to the lung in order to increase the potency of the protective response.
COMPARATIVE ANTI-BACTERIAL IMMUNITY IN THE URINARY TRACT: DOES ONE SIZE FIT ALL?
Funder
National Health and Medical Research Council
Funding Amount
$376,781.00
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 of humans. It is estimated that 40 to 50% of adult healthy women have experienced at least one UTI episode in their lifetime. Bacteria cause most UTI and this study will focus on how these bacteria survive in the urinary tract and will provide key insight into the ways in which human immune responses develop to counteract these bacteria.
Chronic Bacterial Infection And The Generation Of T Cell Memory: Implication For Vaccination Against Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$547,970.00
Summary
Two million people die from tuberculosis (TB) each year. The immune system is unable to eradicate the TB bacterium, and the type of immune response needed to protect against the disease is poorly understood. We will use animal models of TB infection and sophisticated immunological techniques to decipher how the TB bacterium interacts with the immune sytem and causes disease. We will also develop new TB vaccines that aim to boost the immune response in the lung, the main site of TB infection.
Pathogenomics: New Ways To Exploit Genome Sequence Data From Pathogenic Bacteria.
Funder
National Health and Medical Research Council
Funding Amount
$547,372.00
Summary
Bacterial pathogens are locked in an evolutionary battle of survival with their eukaryote hosts. The rapidly evolving genes of medically-important pathogens are generally those required for adaptation to the human host. This project aims to exploit the abundance of available bacterial genome sequences to predict rapid evolution in bacterial pathogens using computational methods. The protein products of such genes offer novel targets for therapeutic intervention.
Structural And Functional Studies On Leptospiral Antigens Central To Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$287,321.00
Summary
Leptospirosis, also known as Weil's disease and canefield fever, is a potentially fatal disease caused by infection with the bacteria Leptospira. Leptospira is able to infect a broad range of animals including livestock and humans. Human infection typically occurs through contact with water or vegetation that has been exposed to the urine of an infected animal. This project focuses on a key step in the bacterial infection in trying to understand how these bacteria adhere to human cells.