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.
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.
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.
Can Skin Infection With Group A Streptococcus Cause Acute Rheumatic Fever?
Funder
National Health and Medical Research Council
Funding Amount
$459,450.00
Summary
It is traditionally taught that the cause of acute rheumatic fever (ARF) is always infection of the throat with the bacterium group A streptococcus (GAS). However, in Aboriginal communities of the Top End of the Northern Territory the incidence of ARF is the highest reported in the world, yet GAS is uncommonly isolated from the throat. There is further information to suggest that GAS skin sores may underlie many cases of ARF. If this were proven, it would completely alter the traditional view of ....It is traditionally taught that the cause of acute rheumatic fever (ARF) is always infection of the throat with the bacterium group A streptococcus (GAS). However, in Aboriginal communities of the Top End of the Northern Territory the incidence of ARF is the highest reported in the world, yet GAS is uncommonly isolated from the throat. There is further information to suggest that GAS skin sores may underlie many cases of ARF. If this were proven, it would completely alter the traditional view of the cause of ARF, and have important implications for prevention of ARF around the world. Presently, these approaches focus on diagnosing and treating sore throat, but no country has proven that such a program can be successful in substantially reducing new cases of ARF. If it was known that skin infection could lead to ARF, then countries (including Australia) could emphasise the importance of skin health programs. A further benefit of this knowledge would be to influence GAS vaccine development, which presently is largely focused on the prevention of sore throat. A different possibility has recently been raised - that the cause of ARF may not always be GAS, but instead that the related bacteria GCS and GGS may have the potential to cause this disease. Proof of this hypothesis would even more dramatically alter our understanding of disease causation, prevention, and vaccine development. We propose to determine the cause of ARF in Aboriginal communities by regularly swabbing families of people with a history of ARF, and using genetic fingerprinting of the bacteria from the skin and throat swabs. When cases of ARF occur, we will be able to determine the site and type of infection that precipitated the attack. We will conduct a related study in more communities, in which we will swab family members of people with ARF and of control families (without ARF) to determine the bacteria most commonly isolated from ARF families.Read moreRead less
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
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.
The aim of this project is to provide a better understanding of the mechanisms underlying the development of gas gangrene, an often fatal disease of particular significance to elderly and diabetic patients, who are particularly susceptible following injury, or surgery, or in some cases when suffering from colon cancer. Although research has been carried out on this disease for many years prompt surgical removal of the infected tissue, often including amputation of a limb, is still commonly used ....The aim of this project is to provide a better understanding of the mechanisms underlying the development of gas gangrene, an often fatal disease of particular significance to elderly and diabetic patients, who are particularly susceptible following injury, or surgery, or in some cases when suffering from colon cancer. Although research has been carried out on this disease for many years prompt surgical removal of the infected tissue, often including amputation of a limb, is still commonly used to ensure the patient's survival. This project involves the study of the two bacteria that are the major causes of the disease. We aim to find out how the bacteria mediate the disease, in particular to determine which toxic factors produced by the bacteria are involved. The normal host response to a bacterial infection is a rapid influx of white blood cells to the infected tissue, which is part of the normal inflammatory response. These cells engulf and degrade the bacteria, clearing the infection. However, a major characteristic of gas gangrene pathology is that very few white blood cells infiltrate the infected tissue. We aim to determine why the host fails to mount an inflammatory response to this bacterial infection. We will achieve this objective by developing a better understanding of the role of the bacterial toxins in the development of this morbid disease. It is hoped the results from this study will enable the development of more effective therapeutic and prophylactic treatments for this disease and also provide a foundation for studies into the modulation of the host response by other bacterial species.Read moreRead less
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.
Characterisation Of The Key Role Played By The Persistent Phase Of Chlamydia Pneumoniae In Disease Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$286,320.00
Summary
Chlamydia pneumoniae is a relatively newly identified pathogen that is responsible for several respiratory conditions such as, pneumonia and chronic obstructive pulmonary disease and has been strongly linked to heart disesae. Serious disease is due to low grade chronic infections, but we do not understand how the bacterium causes these chronic diseases. This project will identify markers of chronic C. pneumoniae infections and relate these to the disease that results. Identifying these markers o ....Chlamydia pneumoniae is a relatively newly identified pathogen that is responsible for several respiratory conditions such as, pneumonia and chronic obstructive pulmonary disease and has been strongly linked to heart disesae. Serious disease is due to low grade chronic infections, but we do not understand how the bacterium causes these chronic diseases. This project will identify markers of chronic C. pneumoniae infections and relate these to the disease that results. Identifying these markers of chronic disease should lead to improved methods of disease control, including new diagnostic tests, vaccines and new drug therapies.Read moreRead less
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