Inhibition Of Haemostasis As A Novel Host-directed Therapy For Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$528,471.00
Summary
Mycobacterium tuberculosis-induced vasculopathy is an important cause of stroke worldwide, and stroke is a common (~20%) complication of tuberculous meningitis, the most dangerous presentation of tuberculosis. Blood clotting may also speed the growth tuberculosis in the body further worsening the situation. We will use zebrafish find out if clotting can be targeted to slow the growth of mycobacteria and then translate our findings to a mouse model of pulmonary tuberculosis.
Genes Of Mycobacterium Tuberculosis Essential For Latent Tuberculosis Infection
Funder
National Health and Medical Research Council
Funding Amount
$590,103.00
Summary
One third of the worlds population is latently infected with M. tuberculosis, the bacteria which causes TB. We have identified key genes in M. tuberculosis that enable the bacterium to shut-down and become latent. This project will investigate these genes, identify their role and yield vital information for a new paradigm of drug and vaccine development. Improved vaccines and drugs which can target and inhibit latency would be of enormous benefit to the global community.
Understanding The Role Of O-linked Glycosylation In Burkholderia Cenocepica For Host Survival Using Proteomic Approaches
Funder
National Health and Medical Research Council
Funding Amount
$222,004.00
Summary
The bacteria Burkholderia cenocepecia (Bc) is a common infection of Cystic Fibrosis suffers in Australia. ~20% CF patients infected with Bc will die due to lung failure. Due to this high death rate there is an urgent need to understand how Bc survives and causes disease in the host. This grant aims to understand how the attachment of sugars, a process known as glycosylation, affects the ability of Bc to survive in mammalian cells.
Host-pathogen Interactions In Clostridial Myonecrosis
Funder
National Health and Medical Research Council
Funding Amount
$897,617.00
Summary
This project will show how the bacteria that cause gas gangrene interact with host cells in an infection. We will examine the expression of genes from both the host and the pathogen in a mouse disease model. The aims are to determine the impact of bacterial genes that are differentially regulated in an infected lesion, how gene expression of both the host and pathogen is modulated throughout the course of an infection and the role of host pathways in controlling the infection process.
The Glyco-interactome Of Pathogenic Neisseria: Understanding Disease And Defining Vaccine Targets
Funder
National Health and Medical Research Council
Funding Amount
$431,012.00
Summary
In order to infect humans and cause disease, many bacteria rely on interactions with carbohydrate (sugar) structures on human cells. This project aims to characterise the sugar interactions that enable Neisseria meningitidis (causes meningitis, sepsis) and Neisseria gonorrhoeae (causes gonorrhoea, associated with infertility and increased transmission of HIV) to cause disease. This will increase our understanding of host-pathogen interactions and aid development of new vaccines and therapeutics.
A Novel CD39-like Ecto-NTPDase Of Legionella Pneumophila
Funder
National Health and Medical Research Council
Funding Amount
$362,046.00
Summary
Legionnaire's disease is a serious cause of community acquired pneumonia. We are studying the way the Legionella bacteria persist in the environment and cause disease. We have found that Legionella produces a specific protein that mimics the action of a human protein. This proposal aims to work out how the bacteria use this protein to infect the human lung and escape killing by immune cells. The results from this study will help to determine if this protein may be used as a target for the develo ....Legionnaire's disease is a serious cause of community acquired pneumonia. We are studying the way the Legionella bacteria persist in the environment and cause disease. We have found that Legionella produces a specific protein that mimics the action of a human protein. This proposal aims to work out how the bacteria use this protein to infect the human lung and escape killing by immune cells. The results from this study will help to determine if this protein may be used as a target for the development of new anti-infective drugs.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.
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
Using Genetic Tools To Study Helicobacter Pylori Pathogenesis And Persistence
Funder
National Health and Medical Research Council
Funding Amount
$316,449.00
Summary
H. pylori infection is the leading cause of gastric ulcer disease and stomach cancer. In light of emerging antibiotic resistance and failed vaccine trials, alternative therapies are needed to treat this lifelong infection. This project aims to develop tools to identify and characterize genes required by H. pylori for infection which will serve as new drug targets. This new knowledge will also contribute to a better understanding of the persistence of this and other bacteria.