The Darwin Prospective Melioidosis Study: Years 27-31
Funder
National Health and Medical Research Council
Funding Amount
$1,281,718.00
Summary
The Darwin Prospective Melioidosis Study has documented 914 cases since 1989, with 115 fatalities. A surge in Darwin melioidosis cases over the past 5 years has been linked to urban development and the discovery of a new bacterial strain. Whole genome sequencing of our unique 25+ year set of bacteria and their linked patient data will unravel the changing epidemiology and identify important virulence factors, forming a foundation for future diagnostics, therapeutics, and vaccines.
The Pathogenesis Of Melioidosis: The Interaction Of Burkholderia Pseudomallei With Host Cells.
Funder
National Health and Medical Research Council
Funding Amount
$344,375.00
Summary
Melioidosis is an often fatal disease of mainly tropical Australia and SE Asia caused by a bacterium which is found in soil and water. Infection occurs via wounds or by inhalation. Melioidosis has recently become endemic in south-west Western Australia and south-eastern Queensland, and could represent an emerging disease worldwide. Melioidosis disproportionately affects Aboriginal Australians. Melioidosis has many forms including septicemia with damage to most organs, particularly lung, spleen a ....Melioidosis is an often fatal disease of mainly tropical Australia and SE Asia caused by a bacterium which is found in soil and water. Infection occurs via wounds or by inhalation. Melioidosis has recently become endemic in south-west Western Australia and south-eastern Queensland, and could represent an emerging disease worldwide. Melioidosis disproportionately affects Aboriginal Australians. Melioidosis has many forms including septicemia with damage to most organs, particularly lung, spleen and liver, acute localised suppurative infection and pneumonia. Melioidosis may also become latent, and later develop into an acute and fatal infection. It is important to understand, at the molecular level, how and why the causative bacterium is able to cause disease. Only with such an understanding can measures be undertaken to prevent the disease, or novel methods developed to control the disease. Colonisation of a host is a first step in the disease process for all bacteria which cause disease. Large protein molecules located on the surface of disease-causing bacteria are usually neccessary for colonisation of the host since they allow adherence to the surface of host cells. We have previously undertaken a basic study of adherence. This study will build on this research with the aim of identifying molecules which mediate adherence to host cells, using in vivo and in vitro methods, including the techniques of molecular biology. This study will inevitably lead to the development of vaccine candidates which is important to the management of melioidosis, particularly in high risk groups. It may also allow the development of novel antimicrobial compounds.Read moreRead less
Evolution Of Pertussis Epidemics And Effect Of Genotypes On Infection Outcomes And Immunisation
Funder
National Health and Medical Research Council
Funding Amount
$657,781.00
Summary
Pertussis, or whooping cough, is caused by Bordetella pertussis. Despite high vaccine coverage, the incidence of pertussis has increased substantially in recent years in Australia. One of the contributing factors is changes in the pertussis strains. This project will determine the genetic composition and virulence characteristics of epidemic strains in Australia and investigate the effect of these strains on disease severity and vulnerability of vaccinated individuals to infection.
The biology, structure and function of bacterial virulence effectors. This project is closely aligned with the National Research Priority of Promoting and Maintaining Good Health and will establish a research framework to investigate novel virulence processes that allow bacterial pathogens to infect humans and cause disease. This fresh approach to the study of bacterial pathogenesis will sit outside classic genetic methods to investigate infection and immunity which rely heavily on genetic manip ....The biology, structure and function of bacterial virulence effectors. This project is closely aligned with the National Research Priority of Promoting and Maintaining Good Health and will establish a research framework to investigate novel virulence processes that allow bacterial pathogens to infect humans and cause disease. This fresh approach to the study of bacterial pathogenesis will sit outside classic genetic methods to investigate infection and immunity which rely heavily on genetic manipulation of the pathogen. Other than providing fundamental information on host-pathogen interactions, this work may lead to novel disease interventions by inhibition of bacterial virulence factor activity and/or enhancement of host inflammatory and immune responses.Read moreRead less
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.
Functional characterisation of poly-histidine triad proteins. This project aims to understand the role and function of a novel family of surface proteins produced by Streptococci. These so-called polyhistidine triad proteins are known to contribute to capacity to cause disease in animals and humans, but we need to know how they work, as they may be excellent targets for novel drugs or vaccines.
Novel perspectives on the function of AB5 toxin B subunits in pathogenic bacterial. AB5 toxins are produced by bacteria that cause important diseases in humans and livestock. This project tests the hypothesis that the components of the toxins responsible for binding to host cells and tissues also directly contribute to cellular damage, thereby providing a better understanding of how AB5 toxin-producing bacteria cause disease.
How bacteria cause disease in the urinary tract. This project will investigate the virulence properties of uropathogenic Escherichia coli, the major causative agent of urinary tract infections (UTI) in humans. The results will help to understand how these bacterial pathogens cause disease and will impact strategies aimed at the prevention and treatment of chronic and recurrent UTI.
A One Health Approach To Assessing The Threat Of Clostridium Difficile To Australia’s Biosecurity: A Genomic Investigation Of Human, Animal And Environmental Isolates
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Clostridium difficile is a bacterium that causes life-threatening diarrhoea in humans and animals and is a major public health issue in Australia. This project will study the genetic make-up of the bacterium and identify factors contributing to the emergence, evolution, and spread of C. difficile. This knowledge will be essential in guiding effective public health interventions and reducing deaths from C. difficile infection in humans and animals.
Role Of The Host Fibrinolytic System In Invasive Group A Streptococcal Disease
Funder
National Health and Medical Research Council
Funding Amount
$531,444.00
Summary
The flesh-eating bacterium group A streptococcus (GAS) is estimated to cause 700 million cases of self-limiting disease, and 600,000 cases of serious invasive disease each year. Approximately 25% of invasive infections are fatal. We have shown that GAS are able to hijack the host fibrinolytoc system to cause severe invasive infections. We plan to further examine the details of how this contributes to GAS disease. This research may contribute to the future devlopment of new therapeutics.