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.
Antibiotic Tolerance And Small RNA Networks In Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$521,559.00
Summary
Treatment of MRSA is restricted to last line antibiotics and treatment failure is associated with an intermediate tolerance to vancomycin. Regulatory molecules termed small RNA mediate responses to antibiotic challenge but their functions are poorly understood. This proposal will profile sRNA function to understand how they adapt S. aureus to antibiotic challenge. A molecular understanding of vancomycin-tolerance will inform development of diagnostics and treatment strategies.
The Pathogenesis Of Infections Caused By Clostridium Sordellii.
Funder
National Health and Medical Research Council
Funding Amount
$400,232.00
Summary
The bacterium Clostridium sordellii causes necrosis and multiorgan failure with a very high mortality rate of 70% in infections of drug users, transplant and post-abortion patients, and 100% for post-partum patients. Little is known about how C. sordellii causes such devastating disease; treatment of these infections is currently ineffective. This project will make a major contribution to our understanding of how disease is caused and may lead to improved prevention and treatment stratetegies.
Multidrug Recognition And Resistance In Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$598,978.00
Summary
Strains of Staphylococcus aureus (Golden Staph), resistant to almost all available anti-staphylococcal agents, are responsible for serious infections among patients; in some hospitals such outbreaks reach epidemic proportions. Resistance has emerged to all classes of antimicrobial agents. We will increase our understanding of proteins that confer resistance by pumping multiple antimicrobials out of the cell to ultimately design more effective antibacterials able to bypass such drug pumps.
Investigation Of The Localisation, Transport And Vaccine Potential Of Group A Streptococcal Cell Surface Proteins.
Funder
National Health and Medical Research Council
Funding Amount
$505,523.00
Summary
Streptococcus pyogenes (group A streptococcus; GAS) is a bacterium that causes human skin and throat infections as well as highly invasive diseases including necrotising fasciitis. Additionally, serious sequeale, including rheumatic fever and acute glomerulonephritis, may result following repeated infection. We have recently examined the GAS cell wall and identified 23 proteins that are surface exposed, 20 of which are novel. We hypothesise that a number of these surface exposed proteins represe ....Streptococcus pyogenes (group A streptococcus; GAS) is a bacterium that causes human skin and throat infections as well as highly invasive diseases including necrotising fasciitis. Additionally, serious sequeale, including rheumatic fever and acute glomerulonephritis, may result following repeated infection. We have recently examined the GAS cell wall and identified 23 proteins that are surface exposed, 20 of which are novel. We hypothesise that a number of these surface exposed proteins represent candidate vaccine antigens capable of conferring protective immunity. We therefore propose to examine these surface proteins as components of experimental vaccines against GAS.Read moreRead less
Non-coding RNA Regulation Of Virulence In Enterohaemorrhagic E. Coli
Funder
National Health and Medical Research Council
Funding Amount
$389,313.00
Summary
Shiga toxins cause potentially fatal haemolytic uremic syndrome (HUS) and are transferred between bacterial pathogens by bacteriophage (bacterial viruses). We have recently found that the Shiga toxin encoding bacteriophage encodes an unusually large number of non-coding RNAs (RNA regulators of gene expression). This Project aims to understand how these RNA regulators benefit the Shiga toxin bacteriophage and use this knowledge to develop interventions that will prevent expression of the toxin.