Molecular Epidemiology Of Mycobacterium Tuberculosis Infection In The Northern Territory, Australia
Funder
National Health and Medical Research Council
Funding Amount
$122,714.00
Summary
The Northern Territory (NT) of Australia has the highest jurisdiction-specific rates of tuberculosis (TB) in Australia, and TB is a disease that disproportionately affects Indigenous people. The factors that contribute to the spread of TB in the NT are incompletely understood. We plan to use technology known as “whole genome sequencing” of bacterial DNA to better the understanding of the spread of TB in the NT. This will help guide TB control policies.
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.
Molecular Typing And Epidemiology Of Bordetella Pertussis In Australia
Funder
National Health and Medical Research Council
Funding Amount
$552,662.00
Summary
Pertussis, commonly known as whooping cough, is an acute respiratory disease caused by Bordetella pertussis. Despite more than half a century of vaccination, pertussis has remained endemic in Australia, causing epidemic outbreaks every 3 to 4 years. Indeed the incidence has been increasing in recent years with over 11,000 cases notified in 2005.Pertussis is the commonest of all vaccine preventable diseases targeted by the Australian standard vaccination schedule. To control pertussis, appropriat ....Pertussis, commonly known as whooping cough, is an acute respiratory disease caused by Bordetella pertussis. Despite more than half a century of vaccination, pertussis has remained endemic in Australia, causing epidemic outbreaks every 3 to 4 years. Indeed the incidence has been increasing in recent years with over 11,000 cases notified in 2005.Pertussis is the commonest of all vaccine preventable diseases targeted by the Australian standard vaccination schedule. To control pertussis, appropriate epidemiological surveillance must be implemented to monitor the circulating B. pertussis strains and emergence of any new strains, in particular those that escape the protection by vaccines. This project will use a novel genomic comparison approach to find variation known as single nucleotide polymorphisms (SNP) present around the genome. We will use these SNPs to analyse a large collection of Australian and worldwide isolates to identify those SNPs most suitable for typing and determine the optimal number of SNPs needed for discrimination. A standardized, consistent and reliable typing method for strain identification will be established. We will further develop an integrated method for detecting known variation in the genes encoding the five acellular vaccine antigens. A combined method for strain identification and detection of antigenic variation will then be developed for culture-independent typing, enabling identification of the strain infecting an individual directly from a clinical sample without the need for culture. This study will establish molecular methods for surveillance of pertussis in Australia, essential for further improvement of acellular pertussis vaccines and public health control measures.Read moreRead less
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.
Reducing Pertussis Burden By Optimising Molecular Epidemiological Surveillance Of Epidemic Bordetella Pertussis In Australia
Funder
National Health and Medical Research Council
Funding Amount
$487,258.00
Summary
Australia has experienced a prolonged epidemic of pertussis from 2008 to 2012 and is currently experiencing another epidemic. In this project, we aim to elucidate the evolutionary dynamics of the epidemics by genome sequencing and develop a practical high throughput culture independent method for epidemiological typing. The outcomes will be highly significant for surveillance of pertussis infections and designing strategies for control and prevention of pertussis.
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.
MECHANISMS AND MARKERS OF TUBERCULOSIS TRANSMISSION WITHIN AUSTRALIA
Funder
National Health and Medical Research Council
Funding Amount
$799,978.00
Summary
Tuberculosis (TB) kills nearly 2 million people each year. The emergence of drug resistant TB in the Asia-Pacific region poses a particular threat to Australia, due to frequent population mixing and ongoing TB transmission that may facilitate its spread within vulnerable communities. The proposed study will develop advanced tools to monitor and limit TB transmission within Australia. It will also provide novel insight into the evolution of the global TB epidemic and key factors that sustain it.