Novel Therapeutic Strategy Against Multidrug-resistant Gram-negative Bacteria
Funder
National Health and Medical Research Council
Funding Amount
$349,823.00
Summary
In the past two decades, there has been a marked decline in discovery and development of new antibiotics while there has been a remarkable increase in resistance to the currently available antibiotics. The growth in the number of resistant bacteria and lack of antibiotics available for treatment is very significant with gram-negative bacteria, such as Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia. Colistin, an old antibiotic that has been used little over the l ....In the past two decades, there has been a marked decline in discovery and development of new antibiotics while there has been a remarkable increase in resistance to the currently available antibiotics. The growth in the number of resistant bacteria and lack of antibiotics available for treatment is very significant with gram-negative bacteria, such as Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia. Colistin, an old antibiotic that has been used little over the last 40-50 years, has been 'taken off the shelf' and is now being used as a last line of defence to treat people with infections caused by these bacteria. Clearly, doctors and their infected patients will be in an even more precarious position than currently exists if resistance to colistin increases. We have discovered a novel therapeutic strategy that is able to reverse colistin resistance in P. aeruginosa. The studies proposed in this project will investigate this novel strategy across a range of multidrug-resistant bacteria and provide the information essential for rational use in patients. We propose that such a novel therapeutic strategy will provide a powerful weapon for the war on these 'superbugs'.Read moreRead less
Investigating A Novel Generic Approach To Anti-Infective Agents
Funder
National Health and Medical Research Council
Funding Amount
$636,833.00
Summary
Alpha helical regions of proteins mediate infection by viruses and bacteria. Short peptides corresponding to these helical segments are unstructured in water. We will (a) test new technology for its generic capacity to stabilize 1-4 turns of alpha helical viral and bacterial peptides, (b) test small molecules for helical structure, and (c) test for antiviral, antibacterial or immunogenicity activity in cell assays. Proof of the technology may benefit many fields of medicine and health prevention ....Alpha helical regions of proteins mediate infection by viruses and bacteria. Short peptides corresponding to these helical segments are unstructured in water. We will (a) test new technology for its generic capacity to stabilize 1-4 turns of alpha helical viral and bacterial peptides, (b) test small molecules for helical structure, and (c) test for antiviral, antibacterial or immunogenicity activity in cell assays. Proof of the technology may benefit many fields of medicine and health prevention.Read moreRead less
Defining Targets For Antifungal Stewardship In Immunocompromised Patients: Optimising Care And Safety
Funder
National Health and Medical Research Council
Funding Amount
$108,902.00
Summary
Patients with impaired immune systems are at risk of serious fungal infections. Antifungal medicines used to prevent and treat these infections can be toxic and costly. This project aims to review current antifungal use and improvement activities in place in health services, assess prescriber knowledge, and to evaluate current doses of echinocandin antifungals used in liver failure patients. This project will identify ways to improve antifungal use needed for effective and safe prescribing.
Exploiting The Pharmacokinetic And Pharmacodynamic Properties Of Bile Acid Receptor Agonists To Treat Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$653,952.00
Summary
We have generated preliminary data suggesting that chemicals made by the liver, called bile acids, act on fat cells to release a hormone called adiponectin. In liver disease adiponectin has favorable effects, including reducing liver inflammation and fibrosis (scarring). By using drugs that mimic the action of bile acids we expect that adiponectin production by fat cells can be increased, creating a new way to treat patients with chronic liver diseases.
Structural Characterisation Of A Natural Inhibitor Of Sporulation Bound To Its Histidine Kinase Target
Funder
National Health and Medical Research Council
Funding Amount
$261,000.00
Summary
Many bacteria, including some which are virulent pathogens such as anthrax (Bacillus anthracis), are able to enter a dormant state by forming spores (sporulation). These spores are extremely robust and may persist in the environment buried in the soil for example for hundreds of years. The initiation of sporulation occurs in response to changes in the cellular and environmental conditions which threaten the free replicating existence of the bacterium. The process of sporulation is controlled at ....Many bacteria, including some which are virulent pathogens such as anthrax (Bacillus anthracis), are able to enter a dormant state by forming spores (sporulation). These spores are extremely robust and may persist in the environment buried in the soil for example for hundreds of years. The initiation of sporulation occurs in response to changes in the cellular and environmental conditions which threaten the free replicating existence of the bacterium. The process of sporulation is controlled at the molecular level by a complex signaling relay. It is of course vital for the existence of the organism that control of sporulation is tightly regulated - preventing the onset of spore-formation in any but the desired circumstances. We aim to determine the three-dimensional structures of the molecules involved in this regulated process and how, by interacting with each other, they can pass on the signal to the bacterium to either start or stop the spore forming process. Ultimately, the results of this work might lead to antibacterial agents which could be used to control particularly dangerous strains of bacteria.Read moreRead less
A Study Of Artemisinin Combination Therapy Given At Delivery To Prevent Postpartum Malaria And To Young Infants To Treat Uncomplicated Malaria
Funder
National Health and Medical Research Council
Funding Amount
$788,850.00
Summary
The proposed studies will investigate the preventive value of a course of combination antimalarial treatment at delivery in pregnant women in malarial areas. The transfer of this treatment into breast milk and to the suckling infant will be investigated since this may protect the infant against malaria but also cause drug-related side-effects. These data will be used, with a study of combination treatment in infants with malaria, to optimise dose regimens in this vulnerable group.
Rescuing The Last-line Therapy Colistin Against Gram-negative ‘superbugs’: Increasing The Therapeutic Index By Attenuation Of Nephrotoxicity
Funder
National Health and Medical Research Council
Funding Amount
$498,631.00
Summary
Antibiotic resistance in Gram-negative ‘superbugs’ is presenting a significant global medical challenge. Colistin (polymyxin E) is increasingly used as the last treatment option even though the current use is suboptimal. Simply increasing the daily dose is not an option due to kidney toxicity. This project focuses on a new approach using antioxidants to ameliorate the potential for colistin-induced kidney toxicity, thereby allowing higher doses to achieve adequate bacterial kill in patients.