A New Class Of Inhibitors For The Treatment Of Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$720,691.00
Summary
Tuberculosis (TB) remains a major cause of mortality and morbidity worldwide, with 1.3 million deaths annually. Some strains of the TB bacterium are resistant to all available drugs. We have identified novel chemical structures that display potent and specific activity against pathogenic mycobacteria. In this proposal we will develop optimised derivatives with more potent activity against mycobacteria, assess their stability and toxicity and determine their mode of action.
An Ace Up Their Sleeve: Characterisation Of A Novel Family Of Drug Efflux Systems Represented By The Acinetobacter AceI Exporter
Funder
National Health and Medical Research Council
Funding Amount
$400,286.00
Summary
Chlorhexidine is widely used as an antiseptic in products such as skin washes, soaps, mouthwashes, disinfectants and preservatives. We have recently discovered a novel bacterial protein which pumps chlorhexidine out of bacterial cells to make them resistant to this antiseptic agent. This proposal aims to understand this resistance mechanism and to find inhibitors which could be applied in clinical settings to augment the activity of chlorhexidine.
Reversing Antibiotic Resistance With Efflux Pump Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$494,174.00
Summary
Antibiotic resistance in dangerous pathogens is one of the greatest threats to human health of the 21st century. The main cause of multidrug resistance is the presence of drug efflux pumps, which remove antibiotics from the bacterial cell thereby lowering the antibiotic concentration inside the cells to sub-toxic levels. We will use our expertise on these efflux pumps and on how to inhibit them to develop compounds that could reverse resistance and restore the activity of antibiotics.
Once treatable infections are becoming deadly because bacteria are developing broad antibiotic resistance. New medicines are urgently needed. Microbes themselves are the richest known source of new antibiotics but finding the 'good bugs' is like finding a needle in a microbial haystack. This project will use state-of-the art science to screen a previously overlooked source of rich microbial biodiversity and find new antibiotics.
Circuit Breaker: Investigating The Regulatory Circuits Controlling Expression Of Drug Efflux Pumps In The Nosocomial Pathogen Acinetobacter Baumannii
Funder
National Health and Medical Research Council
Funding Amount
$515,244.00
Summary
Hospital-acquired infections caused by drug resistant pathogenic bacteria cost billions of dollars and increase patient pain and morbidity. This research will study the genes controlling multidrug efflux pumps in a major hospital-acquired bacterial pathogen, Acinetobacter baumannii. These efflux pumps make the bacteria resistant to antimicrobials by pumping them out of the cell. The results will allow us to better track drug resistant strains and will inform treatment options.
Pacing Across The Membrane: Characterising The PACE Family Of Multidrug Efflux Systems
Funder
National Health and Medical Research Council
Funding Amount
$640,815.00
Summary
The World Health Organisation recognises bacterial antimicrobial resistance as one of the major threats to human health worldwide. Multidrug efflux pumps are an important class of resistance proteins that sit in the bacterial cell membrane and move antimicrobials out of the cell. We recently discovered the first new family of multidrug efflux pumps to be described in 15 years. Our project will define the precise resistance functions of this family and identify ways to block their function.
Potent Lipoglycopeptide Antibiotics Against C. Difficile
Funder
National Health and Medical Research Council
Funding Amount
$750,411.00
Summary
In some people C. difficile bacteria naturally reside in the gut. Other people accidentally ingest spores of the bacteria while they are patients in a hospital or nursing home. Sometimes, broad-spectrum antibiotics used to treat an infection also kill healthy gut bacteria. The gut then becomes overrun with C. difficile, causing diarrhoea and pain, and sometimes death. We will investigate the use of a new potent antibiotic, vancapticin, to kill C. difficle and prevent relapse of infection.
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.
Targeting Nucleic Acid Synthesis And Cell Division In Gram-negative Bacterial Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$966,800.00
Summary
Some bacteria like Acinetobacter species cause infections in hospitals that are difficult to treat because they have acquired resistance to most antibiotics. This project will combine the complementary expertise of five research groups to develop knowledge of, and how to block, three essential processes in these worrying pathogenic species: copying of DNA, RNA synthesis, and cell division. This promises to lead to development of new antibacterial therapies.
Improving Subunit Vaccines Against Tuberculosis For Pulmonary Delivery
Funder
National Health and Medical Research Council
Funding Amount
$635,320.00
Summary
Tuberculosis is an enormous health problem globally and remains a threat to Australia because of our proximity to high burden countries. The development of better vaccines against TB is crucial to reducing disease and preventing transmission. We shall develop and test new TB vaccines composed of a protective TB protein and immune-stimulating molecules in dry powder which can be safely delivered to the lungs. This respirable vaccine will be used to protect against TB and boost the effects of BCG.