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
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.
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.
Rhinovirus impairs physiological and immunological lung development and causes exacerbation of allergic airways disease. Rhinovirus (RV) infections account for around 90 per cent of asthma exacerbations, yet the mechanisms behind this are unknown. This project will use mouse models to study the effects of early life RV infection and allergic sensitisation on respiratory and immunological development, with the expectation that early life RV infection disrupts anitgen presenting cell function.
Coordinate Expression Of Virulence Factors In Pathogenic Escherichia Coli
Funder
National Health and Medical Research Council
Funding Amount
$239,250.00
Summary
Escherichia coli is a versatile pathogen capable of causing a range of disease types including diarrhoea, dysentery, haemolytic uremic syndrome, bladder and kidney infections, septicaemia, pneumoniae and meningitis. Infections due to pathogenic E. coli may be limited to mucosal surfaces or can disseminate throughout the body. Amongst the different classes of pathogenic E. coli, diarrheagenic strains (namely enterotoxigenic and enteroinvasive E. coli) are responsible for the death of an estimated ....Escherichia coli is a versatile pathogen capable of causing a range of disease types including diarrhoea, dysentery, haemolytic uremic syndrome, bladder and kidney infections, septicaemia, pneumoniae and meningitis. Infections due to pathogenic E. coli may be limited to mucosal surfaces or can disseminate throughout the body. Amongst the different classes of pathogenic E. coli, diarrheagenic strains (namely enterotoxigenic and enteroinvasive E. coli) are responsible for the death of an estimated one million humans per year, mainly in third world countries. The majority (80%) of urinary tract infections (UTIs) in humans are caused by E. coli and in Australia alone there are about 250,000 cases per year. It is estimated that one in four women and one in twenty men will develop a urinary tract infection in their lifetime. Pathogenic E. coli strains are normally equipped with multiple virulence factors and there is mounting evidence that the expression of such factors is finely orchestrated by mutual regulatory cross-talk. For example, expression of flagella (which provide motility) and adhesins (which provide attachment) are fundamentally counteracting phenotypes, yet the molecular and genetic mechanisms that coordinate their expression are unknown. I plan to examine inter-system cross-regulation of bacterial surface structures (namely adhesins, autoaggregaters, capsules and flagella). The aim is to understand on the molecular level how microorganisms orchestrate expression of virulence factors and will have consequences for our understanding of microbial pathogenicity. The strategy outlined may lead to new routes for strain attenuation and perhaps a method for vaccine strain construction. The research will be performed in collaboration with international high profile partners.Read moreRead less
Towards Reducing The Susceptibility Of “high Risk” Infants To Allergic Asthma By Therapeutic Modulation Of Immunoregulatory Functions In The Pregnant Mother.
Funder
National Health and Medical Research Council
Funding Amount
$445,681.00
Summary
This project will deliver information in relation to the potential use and underlying modes of action of a therapeutic agent fed to pregnant mothers at high risk for atopic children, to protect against allergic asthma development in their offspring. Furthermore, the project will address the benefits of this therapeutic agent in relation to protection against inflammation induced preterm birth.
Investigation Of The Association Between Chlamydial Infection And Asthma In Different Age Groups
Funder
National Health and Medical Research Council
Funding Amount
$382,117.00
Summary
Asthma is a common and severe lung disease that results from inflammation due to allergy and has symptoms of breathing difficulties, wheezing, chest tightness, and cough. Asthma is clinically characterised by the presence of certain types of responses from the immune system. We are looking for ways of preventing and curing asthma. There is a well known link between certain types of bacteria, called Chlamydia, and asthma but it is not known whether people develop asthma first and then get chlamyd ....Asthma is a common and severe lung disease that results from inflammation due to allergy and has symptoms of breathing difficulties, wheezing, chest tightness, and cough. Asthma is clinically characterised by the presence of certain types of responses from the immune system. We are looking for ways of preventing and curing asthma. There is a well known link between certain types of bacteria, called Chlamydia, and asthma but it is not known whether people develop asthma first and then get chlamydial infection or are infected first and this leads to asthma. We have shown that if adult mice are exposed to an allergen during chlamydial infection then the asthma gets worse. However, if newborn mice have a chlamydial infection then asthma is prevented when they are adults. These are preliminary observations, which we need to expand and understand the immune mechanisms that result in infection and allergy so that we can target them with antibiotics or vaccines. We will investigate how the timing of chlamydial infection relative to exposure to allergens (before, during or after) affects the development of asthma in adult mice. Newborns and young children have different immune systems to adults, so we will investigate what effects the infection of young mice has on infection and allergy later in life. We will also test a new vaccine we have developed against chlamydial infection to see if it can prevent chlamydial infection and infection-induced asthma. We will then examine if there is the same association between chlamydial infection and asthma in human asthmatics that present to hospital with exacerbation of their asthma. This work will help us develop new strategies for preventing and curing asthma, which may vary in different age groups. We will identify whether prevention of chlamydial infection by vaccination (or antibiotics) can be used to prevent and treat asthma.Read moreRead less
The Intracellular Replicative Niche Of Legionella Species And Coxiella Burnetii.
Funder
National Health and Medical Research Council
Funding Amount
$529,632.00
Summary
This project will study how the bacterium that causes Legionnaire's disease survives and grows inside human cells. We have identified new bacterial proteins that allow Legionella to manipulate the normal host cell processes involved in killing an invading bacterium. Similar proteins are also present in the closely related organism, Coxiella, which causes Q-fever. By determining how these proteins act, this work may result in new treatments for Legionnaire's disease and related infections.
Mechanism of action of an anti-inflammatory compound which targets alternatively activated macrophages. The project will study the mechanism by which a novel anti-inflammatory compound, developed by our commercial partner, suppresses the activity of a population of cells known as alternatively activated macrophages. These cells play a key role in driving allergic inflammation, including the inflammation associated with asthma.
Development of microbial bioproducts for the suppression of inflammation. Asthma and inflammatory diseases are serious health problems that result from excessive inflammation. Exposure to bacteria may reduce inflammation. This project will identify the bacterial components that reduce inflammation and develop them into new anti-inflammatory therapies for asthma.