Intracellular Survival Of Burkholderia Pseudomallei And Evasion Of Autophagy
Funder
National Health and Medical Research Council
Funding Amount
$450,799.00
Summary
Melioidosis is a disease with high mortality that is caused by the bacterium Burkholderia pseudomallei. Autophagy is a natural part of the mammalian immune system. This project seeks to explain how Burkholderia pseudomallei avoids killing by host autophagy and identify the bacterial factors necessary for its survival within cells. The identified genes will be future targets for medical intervention.
The Economics Of Reducing The Risk Of Healthcare-acquired Intravascular Device Related Bloodstream Infections
Funder
National Health and Medical Research Council
Funding Amount
$119,500.00
Summary
Approximately one in ten patients will acquire an infection after admission to hospital. Patients will have their hospital stay prolonged during which time they will employ scarce health care resources that might otherwise have been made available to others in need, they will suffer additional pain and anxiety, they will take longer to recuperate after discharge using primary care and outpatient services more intensively and there is a sevenfold increase in the chance of dying in hospital as a r ....Approximately one in ten patients will acquire an infection after admission to hospital. Patients will have their hospital stay prolonged during which time they will employ scarce health care resources that might otherwise have been made available to others in need, they will suffer additional pain and anxiety, they will take longer to recuperate after discharge using primary care and outpatient services more intensively and there is a sevenfold increase in the chance of dying in hospital as a result of an infection. There will be other social costs as those affected take longer to return to their normal economic activities. The aggregate economic burdens imposed by healthcare-associated infection in the US are valued at $AU 11.3 Billion and $AU 3.1 in the UK. Research in currently underway to estimate the economic costs to Australia. One type of hospital infection are those that affect the blood and many are caused by invasive devices. At least 3,500 patients are affected each year in the Australia. The human and financial costs of these particular infections are significant. These infections can be prevented but the preventive activities are costly. The purpose of this research is to systematically evaluate the cost and effectiveness of all known infection control interventions to identify those which offer the best value for money. Furthermore we propose to identify the efficient investment in infection control activities, a point where the economic benefit is equalised with economic cost. This research will identify how much to invest in infection control and the specific interventions to which these investments should be directed. Efficient infection control will save lives, improve outcomes for patients, reduce the period of recuperation, and reduce the significant economic costs to both the patient and the health care system.Read moreRead less
Characterising The Role Of Streptokinase Polymorphism In Invasive Pathogenesis Of Streptococcus Pyogenes.
Funder
National Health and Medical Research Council
Funding Amount
$480,535.00
Summary
Invasive bacterial pathogens such as Streptococcus pyogenes, can hijack host proteins and use them to facilitate the disease process. S. pyogenes secrete streptokinase to activate a host protease (plasminogen) which is used by the bacterium to invade through host tissue. This project will characterise the molecular mechanisms involved in streptokinase mediated activation of plasminogen which will assist the generation of novel therapeutics to treat invasive diseases.
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
The pneumococcus is a major cause of bacterial pneumonia, sepsis and meningitis especially in children and the elderly. Antibiotic-resistant pneumococci are becoming more prevalent, and available vaccines have major shortcomings. We propose to identify and characterise the factors produced by this organism during infection that enable it to cause invasive disease. Such factors could be incorporated into protein-based pneumococcal vaccines currently under development.
Utilisation Of The Human Plasminogen Activation System By Group A Streptococci: Contribution To Virulence And Disease
Funder
National Health and Medical Research Council
Funding Amount
$254,250.00
Summary
Streptococcus pyogenes (group A streptococci; GAS) is a bacterium which causes human skin and throat infections as well as highly invasive diseases including the flesh eating disease necrotising fasciitis. Additionally, serious sequelae, including rheumatic fever and acute glomeulonephritis, may result following infection. Such diseases cause high morbidity and mortality in Aboriginal populations and are a continual significant drain on the national health fund. An important mode of invasion by ....Streptococcus pyogenes (group A streptococci; GAS) is a bacterium which causes human skin and throat infections as well as highly invasive diseases including the flesh eating disease necrotising fasciitis. Additionally, serious sequelae, including rheumatic fever and acute glomeulonephritis, may result following infection. Such diseases cause high morbidity and mortality in Aboriginal populations and are a continual significant drain on the national health fund. An important mode of invasion by GAS may be related to their ability to capture and activate host plasminogen via surface-associated or secreted plasminogen binding proteins (receptors). Plasminogen can be activated by host activators or secreted GAS streptokinase to the potent enzyme plasmin which is responsible for the degradation of tissue barriers. Thus, GAS may utilise plasmin to destroy tissue barriers and invade host tissues. The characterisation of the interaction between GAS and the plasminogen activation system would clarify the role of this system in invasive disease and provide potential targets for therapeutic intervention.Read moreRead less