How Burkholderia Pseudomallei Subverts Host Ubiquitination And Autophagy Pathways
Funder
National Health and Medical Research Council
Funding Amount
$472,260.00
Summary
Burkholderia pseudomallei is a bacterial organism found in soil and water that is the causative agent of melioidosis, a serious invasive disease of humans and animals occurring in tropical areas including northern Australia. Mortality is high owing to only limited treatment options being available. By defining the molecular mechanisms how B. pseudomallei evades removal from infected cells, we aim to identify specific bacterial targets that may form the basis of future prevention strategies.
Host-pathogen Interactions In Burkholderia Infection
Funder
National Health and Medical Research Council
Funding Amount
$490,322.00
Summary
Melioidosis is a fatal tropical disease caused by a bacterium Burkholderia pseudomallei. We found that when the bacterium infects macrophage-like cells in culture (that normally kills bacteria), the cells turn into a cell like an osteoclast, a cell that normally degrades bone. Since an osteoclast is unable to kill bacteria, we speculate that the bacterium subverts the macrophage differentiation pathway and directs the cells into a state where it is unable to attack the invading bacteria.
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.
Nasal Epithelium As A Portal Of Entry For Burkholderia Pseudomallei, With Special Reference To Neurological Melioidosis
Funder
National Health and Medical Research Council
Funding Amount
$536,419.00
Summary
Melioidosis is a potentially fatal disease of manly tropical Australia and SE Asia and an emerging disease worldwide. It disproportionately affects indigenous Australians. It is caused by a bacterium found in soil and water and infection may be by inhalation in the rainy season. One manifestation of melioidosis is neurological symptoms. This project seeks to establish sites and pathways of infection resulting from inhalation, including the pathway from nasal mucosa to brain.
An Investigation Into The Importance Of Potable Water As A Source Of Melioidosis In Northern Australia
Funder
National Health and Medical Research Council
Funding Amount
$362,036.00
Summary
Melioidosis is a potentially fatal infection that occurs throughout the Top End. Infection usually sets in after exposure to contaminated soil or surface water. A recent outbreak of melioidosis in which three of seven cases died was traced to the community's drinking water supply. Subsequent improvements to the community's drinking water treatment appear to have brought the outbreak under control. However, the ability of the bacteria responsible for this infection to survive within the body for ....Melioidosis is a potentially fatal infection that occurs throughout the Top End. Infection usually sets in after exposure to contaminated soil or surface water. A recent outbreak of melioidosis in which three of seven cases died was traced to the community's drinking water supply. Subsequent improvements to the community's drinking water treatment appear to have brought the outbreak under control. However, the ability of the bacteria responsible for this infection to survive within the body for many years before causing late onset infection means that further cases may be recorded in the affected community for years to come. This project aims to assess whether the drinking water supply to other rural communities presents a risk of melioidosis throughout the Top End. Drinking water supplies will be tested for the presence of the bacteria that cause melioidosis. Genetic fingerprinting will be used to compare each strain isolated from water specimens with strains obtained from infections previously diagnosed in hospitals throughout the Top End. This will involve the combined efforts of researchers in Western Australia, the Northern Territory and Queensland. Comparison of these results with standard measures of drinking water quality will enable the research team to work out whether any routinely performed tests can be used as a guide to melioidosis risk. The team will also examine whether any geographical features such as deep water supply or the type of vegetation present can be used to assess melioidosis risk. A clearer picture of melioidosis risk will make it easier to target the delivery of preventive methods such as chlorination or alternatives to specific water supplies. Preliminary studies in Western Australia suggest that primary prevention of melioidosis may be possible. We need to see how widely those findings apply. It is hoped that this work will lead to a significant reduction in the risk of contracting this disease throughout the endemic region.Read moreRead less
ROLE OF PROTEASE ACTIVATED RECEPTORS IN CYSTIC FIBROSIS LUNG PATHOLOGY
Funder
National Health and Medical Research Council
Funding Amount
$176,521.00
Summary
Cystic fibrosis is a major debilitating disease which eventually kills those with the genetic defect. The lungs of patients become infected with the bacteria Pseudomonas aeruginosa or Burkolderia cepacia which initiate a chronic and vicious cycle of inflammation resulting in lung failure. Proteases released by the organisms as well as host cells (neutrophils) involved in clearing the infections play a major role in this cycle by causing the release of molecules (cytokines and mediators) from the ....Cystic fibrosis is a major debilitating disease which eventually kills those with the genetic defect. The lungs of patients become infected with the bacteria Pseudomonas aeruginosa or Burkolderia cepacia which initiate a chronic and vicious cycle of inflammation resulting in lung failure. Proteases released by the organisms as well as host cells (neutrophils) involved in clearing the infections play a major role in this cycle by causing the release of molecules (cytokines and mediators) from the respiratory epithelium. These, in turn, stimulate the movement of neutrophils from the blood to the lung where damage then ensues. How these proteases stimulate release is unclear but studies suggest other proteases involved in inflammation induce release through their interaction with a novel group of protease activated receptors (PAR). In this study, we wish to determine whether PAR are activated or inactivated by host and bacterial proteases commonly seen in the lungs of CF patients. If PAR are activated, it may be possible to develop antagonists which target specific PARS to modulate respiratory epithelial cell function. If inactivated, preservation by adjunct protease inhibitor treatment may be highly beneficial. We will use in vitro technology and cells derived from non-CF and CF patients. This study has great potential in the development of adjunct anti-inflammatory therapy for the treatment of both CF and other inflammatory lung diseases.Read moreRead less
Characterisation Of Cell-mediated Immune Responses In Burkholderia Pseudomallei Infection
Funder
National Health and Medical Research Council
Funding Amount
$239,250.00
Summary
The bacterium Burkholderia pseudomallei, causes a life threatening condition known as melioidosis. Melioidosis is emerging as an important infectious disease in tropical regions of Australia and South East Asia. Death rates following acute disease are extremely high. Despite the importance of B. pseudomallei in tropical public health, very little is known regarding how the body's defence mechanisms prevent the spread of infection. The wide distribution of melioidosis in tropical Australia and ot ....The bacterium Burkholderia pseudomallei, causes a life threatening condition known as melioidosis. Melioidosis is emerging as an important infectious disease in tropical regions of Australia and South East Asia. Death rates following acute disease are extremely high. Despite the importance of B. pseudomallei in tropical public health, very little is known regarding how the body's defence mechanisms prevent the spread of infection. The wide distribution of melioidosis in tropical Australia and other parts of the world, and the lack of basic scientific information regarding this disease, has prompted this study. The bacterium lives within the body's cells and therefore does not respond well to standard antibiotic treatment. Although some of the basic immune mechanisms have been identified, how protection to the organism develops remains unclear. In this project we will investigate the effect of B. pseudomallei on immune cells or lymphocytes. This study will determine the patients' immune responses to the bacteria causing the disease. Our research team has already successfully carried out work on several different aspects of melioidosis. The characterisation of the basic immune function determined in the proposed study will provide the scientific basis for improvement in treatment and the development of possible preventive strategies against melioidosis.Read moreRead less
Diversity And Virulence Determinants Among 1000 Clinical And Environmental Isolates Of Burkholderia Pseudomallei
Funder
National Health and Medical Research Council
Funding Amount
$517,639.00
Summary
Melioidosis is an important infection in tropical northern Australia. It is a common cause of fatal pneumonia and blood infection in the region. Melioidosis results from infection with a soil bacterium. This project builds on the existing melioidosis collaboration between researchers in northern Australia and overseas to determine how the melioidosis bacterium can be so virulent and whether only a subset of the melioidosis bacteria found in the environment are capable of infecting humans.