Evolutionary Events Shaping The Genome Of Cryptococcus Neoformans And Their Effects On Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$387,489.00
Summary
Recurring infection in patients with fungal meningitis caused by Cryptococcus neoformans is typically caused by persistence of the original infection rather than reinfection with a new strain. Our analysis of relapse strains shows that small-scale alterations frequently occur at the chromosome ends - regions containing important pathogenesis-related genes in other pathogens. We seek to characterise this microevolution further to understand how it contributes to the success of this pathogen.
Targeting Fungal Phospholipid Metabolism For Antifungal Drug Discovery
Funder
National Health and Medical Research Council
Funding Amount
$828,557.00
Summary
Invasive fungal infections are a serious and escalating health problem. They cause severe disease with a high death rate and are very costly to the health system. New antifungal drugs with novel properties are needed now because there are problems with current drugs. This project aims to develop potent new antifungal drugs that are effective in many fungal diseases and are well-tolerated.
The Role Of Fatty Acid Metabolism In Pathogenicity.
Funder
National Health and Medical Research Council
Funding Amount
$540,075.00
Summary
Fungi which infect humans are a major health problem, especially for those with compromised immune systems (eg. AIDS, transplant and cancer patients). Pathogenic fungi must evade the host s immune system whilst deriving nutrients for growth. Some fungi evade the immune system by residing within host cells. This poses significant challenges to growth due to the nutrient poor environment. By understanding how these fungi adapt to growth inside host cells, new avenues for treatment will emerge.
Molecular Mechanisms Of Intracellular Growth, Survival And Pathogenicity
Funder
National Health and Medical Research Council
Funding Amount
$335,816.00
Summary
Fungi which infect humans are a major health problem, especially for those with compromised immune systems (eg. AIDS, transplant and cancer patients). These fungi cause disease by evading the immune system whilst deriving nutrients for growth. Some fungi evade the immune system by residing within host cells; a hostile and nutrient poor environment. This project will study a pathway that we have shown is required for growth inside host cells. This knowledge will open new avenues for treatment.
Cryptococcal Phospholipases: Structure, And Potential Targets For Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$511,650.00
Summary
Mortality and morbidity from invasive fungal infections have increased substantially over the past two decades, especially in immunocompromised patients, such as those with AIDS. Antifungal drugs marketed at present are not very effective or are toxic. There is a need to identify new metabolic and structural targets, some of which are responsible for fungal virulence, as potential areas for development of new drugs. One such virulence factor discovered in our laboratory is an enzyme secreted by ....Mortality and morbidity from invasive fungal infections have increased substantially over the past two decades, especially in immunocompromised patients, such as those with AIDS. Antifungal drugs marketed at present are not very effective or are toxic. There is a need to identify new metabolic and structural targets, some of which are responsible for fungal virulence, as potential areas for development of new drugs. One such virulence factor discovered in our laboratory is an enzyme secreted by the pathogenic fungus, Cryptococcus neoformans, which is acquired by inhalation into the lungs where it can cause lesions, and eventually spreads to other parts of the body, including the brain (median mortality, 17%). This enzyme breaks down cell membranes, aiding invasion into the host lungs and other tissues, and is called phospholipase B (PLB). It is also produced by several other pathogenic fungi, and is different from human phospholipases. In this project we aim to understand how the PLB is constructed, so that we can work out where the cell membrane components bind to it. We will then design drugs which can bind to the PLB enzyme in place of membrane components and in this way block its harmful effects. We will test the effects of such drugs to make sure they do not interfere with human enzyme systems. Inhibitory compounds may also be able to kill the cryptococcal cells, especially if administered together with currently used therapies. Drugs developed to treat Cryptococcus will then be applicable to other systemic fungal infections - a major advance in the treatment of fungal disease, and a saving of some A$60,000 per patient (estimated from a recent U.S. study).Read moreRead less