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
Functional Characterisation Of The SseK/NleB Family Of Type III Secreted Effectors In Salmonella And E. Coli
Funder
National Health and Medical Research Council
Funding Amount
$510,183.00
Summary
Salmonella and E. coli cause enteritis and diarrhoea in a large proportion of the world's population including Australia. Certain strains of Salmonella also cause a more serious disease called typhoid fever. Together, diseases caused by Salmonella and E. coli are a major cause of illness and death. In order to cause disease Salmonella and E. coli use a specialised apparatus that functions like a needle and syringe to inject Salmonella proteins into human cells. These proteins that are injected i ....Salmonella and E. coli cause enteritis and diarrhoea in a large proportion of the world's population including Australia. Certain strains of Salmonella also cause a more serious disease called typhoid fever. Together, diseases caused by Salmonella and E. coli are a major cause of illness and death. In order to cause disease Salmonella and E. coli use a specialised apparatus that functions like a needle and syringe to inject Salmonella proteins into human cells. These proteins that are injected into human cells actively reprogram human cells to benefit the disease causing bacteria. We have recently discovered a new family of injected proteins and we aim to determine how these new proteins reprogram human cells and what this contributes to diarrhoea and typhoid fever. This information may lead to the development of more effective treatments for these important diseases.Read moreRead less
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.
Novel Perspectives On The Function Of AB5 Toxin B Subunits
Funder
National Health and Medical Research Council
Funding Amount
$1,041,896.00
Summary
AB5 toxins are important virulence factors of pathogenic bacteria. They comprise pentameric B subunits that bind to target cell surfaces and catalytic A subunits that damage host cell functions. This proposal examines a new paradigm wherein the B subunits are significant contributors to cell damage. We will characterize the cytopathic properties of diverse B subunits, particularly those of emerging toxins. This will provide novel insights into pathogenesis and inform development of therapeutics.
Integrated Bacterial Genomics And Virulence Analysis Of Uropathogenic Streptococcus Agalactiae
Funder
National Health and Medical Research Council
Funding Amount
$747,457.00
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 in humans. Streptococcus agalactiae is an important cause of gram-positive bacterial UTI. We will study the genomes and functions of specific genes in reference strains of this bacterium isolated from patients with different forms of infection to elucidate how bacterial genes and virulence factors contribute to these types of infections.
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.
Capsule Synthesis And Tyrosine Phosphorylation In Streptococcus Pneumoniae
Funder
National Health and Medical Research Council
Funding Amount
$587,803.00
Summary
The bacterium Streptococcus pneumoniae causes much morbidity and mortality worldwide. Antibiotic resistance and vaccination is problematic. New anti-infectives are required. We will study proteins (CpsB, CpsC, CpsD) that regulate polysaccharide capsule synthesis to understand their interactions, and to identify drugs that inhibit CpsB and CpsD. We will also investigate the wider role of tyrosine phosphorylation in the bacterium and investigate how this intersects with capsule synthesis.