Targeting Polymyxin-resistant Gram-negative Superbugs: Development Of Novel Antimicrobial Lipopeptides
Funder
National Health and Medical Research Council
Funding Amount
$661,069.00
Summary
Prevalence of resistance to antibiotics among Gram-negative 'superbugs' is a major global medical challenge, which is highlighted by the Bad Bugs, No Drugs campaign of the Infectious Diseases Society of America. There are virtually no new antibiotics in the current drug development pipeline for these dangerous pathogens. In this project, novel lipopeptides will be designed, synthesised and evaluated against these 'superbugs'. Information obtained will be crucial for further drug development.
Novel Octapeptin Antibiotics Targeting Extremely Drug Resistant 'superbugs'
Funder
National Health and Medical Research Council
Funding Amount
$946,024.00
Summary
The World Health Organization (WHO) has identified antimicrobial resistance as one of the three greatest threats to human health. Many clinicians worldwide have already been confronted with the reality of infections caused by extremely drug resistant (XDR) bacterial 'superbugs' resistant to all available antibiotics. This project aims to develop safe and efficacious octapeptin antibiotics for the treatment of life-threatening infections caused by problematic XDR ‘superbugs'.
Polymyxin-like Lipopeptide Antibiotics Of The Future
Funder
National Health and Medical Research Council
Funding Amount
$335,323.00
Summary
Polymyxins are now being clinically used as the ‘last-line’ therapy for infections caused by multidrug-resistant Gram-negative ‘superbugs’. For the first time our novel approach will interface chemistry and biology of the polymyxins with the purpose of creating a new generation of safer and more efficacious polymyxin antibiotics.
The Hunt For New-generation Lipopeptide Antibiotics Targeting Gram-negative ‘Superbugs’
Funder
National Health and Medical Research Council
Funding Amount
$473,477.00
Summary
The dry antibiotic discovery and development pipeline, together with the increasing incidence of bacterial resistance in the clinic has been dubbed ‘the perfect storm’. This project involves the design, synthesis and preclinical evaluation of a new generation of polymyxin-like lipopeptides that have low nephrotoxicity and specifically target polymyxin-resistant Gram-negative ‘superbugs’.
The Molecular Basis Of G Protein Coupled Transport
Funder
National Health and Medical Research Council
Funding Amount
$495,938.00
Summary
G proteins are molecular switches in all organisms, turning fundamental processes on and off . Defects in the functions of these switches can lead to severe diseases, such as cancer. Crucial details regarding the mechanism by which these switches are turned to on are still missing. This proposal will use a bacterial model system, with aims to provide structural and functional detail on the molecular mechanism of the switch in G proteins, and to extend this model to mammalian systems.
The Development Of Novel Antibacterials Targeting Clostridium Difficile Infections
Funder
National Health and Medical Research Council
Funding Amount
$750,546.00
Summary
Clostridium difficile is a bacterium associated with infections in the gut which may result in mild to severe diarrhoea and inflammation of the colon. These infections are an increasing problem for hospitalised patients in the US, the EU and Australia. We have been very successful in the past at developing new drugs to treat external infections caused by resistant strains of bacteria, for example, golden Staph. We now aim to develop our drugs to treat C. difficile infections in the gut.
Assessing The Biogeography Of The Ocular Microbiota And The Impact Of Antibiotic Prophylaxis
Funder
National Health and Medical Research Council
Funding Amount
$314,644.00
Summary
Using DNA sequencing, recent studies have identified a diverse community of bacteria on the eye, once believed to be sparsely populated by microbes. This project will identify what is the resident bacteria of the eye and where these bacteria reside on the eye. Also, after cataract surgery some individuals experience dry eye problems. This project will investigate if antibiotic therapy, necessary to prevent infection, disrupts the microbial communities on the eye leading to development of dry eye
Design, Development And Analysis Of New Tuberculosis Drugs
Funder
National Health and Medical Research Council
Funding Amount
$736,628.00
Summary
Serious issues of drug resistance have emerged in tuberculosis prevention and are placing enormous pressure on global health systems. We have identified an enzyme of M. tuberculosis that is essential for its survival. This project will develop potent inhibitory compounds for this enzyme. Further, we will identify new drug targets through a screen to specifically identify the genes of the organism essential for its survival in the body. This information will be used to develop new TB drugs.
Developing Species-specific, Structure-targeting Peptides As A Novel Class Of Antibiotics
Funder
National Health and Medical Research Council
Funding Amount
$607,967.00
Summary
Multidrug, antibiotic resistance is a serious global threat. It is a real possibility that in the absence of new antibiotics, common infections could soon become untreatable. This project will develop a novel class of antibiotics that target the core structures of essential bacterial proteins. The successful outcome of this work will also aid the development of specific peptide-based inhibitors for numerous additional diseases, including viral and fungal infections and cancer.
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.