Understanding The Role Of The Essential Regulator WalKR In Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$555,239.00
Summary
Staphylococcus aureus is one of the most common human bacterial pathogens. This project aims to characterise an important global control system in S. aureus, and determine if chemical inhibitors of this control system could be used to treat S. aureus disease in the future.
Optimisation Of Salmonella Genotyping And Epidemiological Data Analysis For Detection And Investigation Of Outbreaks
Funder
National Health and Medical Research Council
Funding Amount
$508,051.00
Summary
Bacteria known as salmonella are the most important causes of food-borne diarrhoeal disease. They occasionally cause potentially fatal septicaemia, especially in young children and people with underlying disease. We estimate that more than 80,000 cases of salmonella infection occur in Australia, each year, at a cost to the community of $37 million. Salmonella are divided into more than 2000 different types, but one - called Typhimurium - causes about 40% of infections and a few others cause most ....Bacteria known as salmonella are the most important causes of food-borne diarrhoeal disease. They occasionally cause potentially fatal septicaemia, especially in young children and people with underlying disease. We estimate that more than 80,000 cases of salmonella infection occur in Australia, each year, at a cost to the community of $37 million. Salmonella are divided into more than 2000 different types, but one - called Typhimurium - causes about 40% of infections and a few others cause most of the rest. This means that is difficult to distinguish cases of salmonella infection that have originated from one source (an outbreak) from cases that have originated from another. Without this information, is it hard to track the source, which is usually inadequately cooked meat or chicken another food that has been contaminated with salmonella after preparation. There are several existing methods for fingerprinting salmonella, but they are quite slow or do not distinguish different strains well enough to identify outbreaks quickly. This means that sources of contaminated food are often not identified in time to prevent more cases occurring. We aim to develop a faster and more discriminatory system for fingerprinting salmonella, based on novel technology that can identify many small genetic sequences that occur in different combinations in different strains. As well, we will develop electronic scanning tools that will link the fingerprints of the salmonella strains with information about the people infected with them, such as the types of food and places where they have eaten, to identify patterns or clusters that indicate a common source. The more rapidly this can be done the sooner the source of contaminated food can be found and eliminated and additional cases can be prevented. This has important implications for public health - it will increase food safety and reduce illness and economic loss.Read moreRead less
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.
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.
Exploitation Of Bacterial Transcription Initiation As A Target For New Antimicrobials
Funder
National Health and Medical Research Council
Funding Amount
$540,356.00
Summary
Antibiotic resistant infections from 'superbugs' are a major health problem. We will exploit information we have gathered on the machinery that copies genetic information into a message to discover chemical compounds that can be used for the development of new antibiotics with a novel mechanism of action.
Determining The Bacterial Contributions To Tuberculosis And Identification Of Drug Targets
Funder
National Health and Medical Research Council
Funding Amount
$443,946.00
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.
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.
Developing New Therapies To Combat Tuberculosis Through Inhibition Of Vitamin B5 Metabolism In The Organism That Causes The Disease
Funder
National Health and Medical Research Council
Funding Amount
$311,760.00
Summary
The metabolism of vitamin B5 by pathogenic microorganisms has been recognised as an attractive target for developing drugs to combat various infectious diseases. The aim of the proposed work is to develop inhibitors of vitamin B5 metabolism in the bacterium that causes tuberculosis, using a powerful, multidisciplinary approach known as “fragment-based drug discovery”. This work is likely to yield potent inhibitors of the target bacterium, which could ultimately be used to treat tuberculosis.