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.
Investigating The Antimicrobial Activity Of Zinc At The Host-pneumococcal Interface
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Streptococcus pneumoniae is a human-only bacterium that is responsible for killing more than one million people every year. This project will analyse how the human immune system fights this bacterium, and subsequently, how the bacteria manages to subvert these attacks and survive in the human host. This will provide crucial information for developing new drugs against this pathogen, in an attempt to combat the ever-increasing problem of antibiotic resistance.
Impact Of Pneumococcal Vaccination And Environmental Factors On Pneumococcal Carriage And Disease.
Funder
National Health and Medical Research Council
Funding Amount
$455,872.00
Summary
Pneumonia is the leading killer of children <5y of age worldwide, and the pneumococcal bacterium is a common cause. Pneumococci are carried in the noses of healthy children. In this project we will determine 1) whether carriage can be used to monitor the impact of vaccination in resource-poor settings, 2) the effect of new vaccines on ear disease and transmission using infant mouse models and 3) if exposure to smoke effects the ability of pneumococci to cause disease and altered gene expressi ....Pneumonia is the leading killer of children <5y of age worldwide, and the pneumococcal bacterium is a common cause. Pneumococci are carried in the noses of healthy children. In this project we will determine 1) whether carriage can be used to monitor the impact of vaccination in resource-poor settings, 2) the effect of new vaccines on ear disease and transmission using infant mouse models and 3) if exposure to smoke effects the ability of pneumococci to cause disease and altered gene expression.Read moreRead less
Novel Insights Into The Molecular Mechanisms Of Manganese Recognition And Acquisition By Pathogenic Bacteria.
Funder
National Health and Medical Research Council
Funding Amount
$843,035.00
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 $4 billion annually. This proposal aims to define the molecular basis of how bacteria scavenge manganese from the host environment. This knowledge will provide the foundation for next generation antimicrobial therapeutics.
Evaluation And Optimisation Of Paediatric Vaccination Programs In Australia And The Region
Funder
National Health and Medical Research Council
Funding Amount
$293,426.00
Summary
Vaccines are highly effective in preventing infection. Increasing numbers of vaccines are available to children and to national immunisation programs. Research is required to ensure that vaccines included in national programs are effective and safe. We must also understand why some children are not vaccinated and to assess ways to improve uptake. Focusing on two common disease, influenza and pneumococcal disease, this fellowship will address these unanswered questions.
Construction And Immunogenic Evaluation Of Hepatitis B Virus Like Particles Expressing T And B Cell Epitopes Of Streptococcus Pneumoniae For The Prevention Of Hepatitis B And Pneumococcal Mediated Otitis Media In Australian Indigenous Children.
Funder
National Health and Medical Research Council
Funding Amount
$500,637.00
Summary
Australian Indigenous children suffer abormally high levels of middle ear infections (term otitis media). In many cases the infections become chronic and have a severe dischage. We propose to make a novel vaccine that will protect these children against a major bacterial cause of the ear infection as well as against hepatitis B virus infection as well.
The Molecular Physiology Of Streptococcus Pneumoniae During Sepsis
Funder
National Health and Medical Research Council
Funding Amount
$232,504.00
Summary
The project will determine the way in which pneumococcus changes its properties when it invades the bloodstream of the human host. Since these changes are linked to sepsis then this new understanding will provide information that can be used to manage and control acute pneumococcal infection.
Zinc: The Molecular Basis Of It�s Toxicity To Gram-positive Pathogens And It�s Exploitation By The Innate Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$588,398.00
Summary
Zinc in excess is toxic to bacteria, and the release of zinc is an important part of the immune response. Dietary zinc deficiency leads to increased susceptibility to pathogenic bacteria. How zinc affords protection has remained a mystery. We have identified a novel mechanism in 2 priority human pathogens by which zinc competes for the essential metal ion manganese. We will elucidate the molecular details of this mechanism and how it is harnessed by the immune system.
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
GENETIC ANALYSIS OF POLYSACCHARIDE CAPSULE BIOSYNTHESIS AND REGULATION IN STREPTOCOCCUS PNEUMONIAE
Funder
National Health and Medical Research Council
Funding Amount
$377,036.00
Summary
Streptococcus pneumoniae (the pneumococcus) is an important cause of invasive diseases such as pneumonia, meningitis and bacteraemia in humans. Many people carry this organism in the nasopharynx asymptomatically. However, in a small proportion, the organism overcomes host defences and invades the body causing life-threatening disease. An essential virulence factor of the pneumococcus is the polysaccharide capsule which protects it from the immune defences of the host during an infection. Until r ....Streptococcus pneumoniae (the pneumococcus) is an important cause of invasive diseases such as pneumonia, meningitis and bacteraemia in humans. Many people carry this organism in the nasopharynx asymptomatically. However, in a small proportion, the organism overcomes host defences and invades the body causing life-threatening disease. An essential virulence factor of the pneumococcus is the polysaccharide capsule which protects it from the immune defences of the host during an infection. Until recently, very little was known of the pneumococcal genes involved in production of this antigen. This project aims to continue characterization of these genes, and examination of the factors which regulate their expression. This regulatory mechanism may be very important, because production of increased levels of the polysaccharide capsule is believed to be an crucial step in the transition from carriage to invasion. An understanding of the molecular events involved in biosynthesis and regulation of capsule production will improve our understanding of the disease process and identify alternative targets for antimicrobial therapy.Read moreRead less