Role In Disease Of A Novel Epigenetic Regulator Associated With The Hypervirulent Neisseria Meningitidis Clonal Complex 41/44
Funder
National Health and Medical Research Council
Funding Amount
$403,249.00
Summary
Neisseria meningitis is a major cause of meningococcal septicaemia and meningitis worldwide. We have identified a phase variable DNA methyltransferase present in disease isolates, some of which have caused meningococcal epidemics. This methyltransferase is involved in the regulation of proteins involved in infection and disease processes. We will investigate whether this regulation increases the ability of the bacteria to adapt to changing host environments and cause disease.
Molecular Epidemiology And High Resolution Surveillance Of Salmonella Enterica Serovar Typhimurium In Australia
Funder
National Health and Medical Research Council
Funding Amount
$583,180.00
Summary
Salmonella typhimurium is a leading cause of the food-borne disease – salmonellosis. It is responsible for considerable morbidity and has an enormous economic cost. Molecular typing is the key to rapidly identify and control outbreaks. This project will employ next generation sequencing technology to develop a new molecular typing scheme. A surveillance system that integrates molecular typing data and epidemiological data will be developed for outbreak investigation and disease prevention.
Optimising Temporal Genomic Surveillance Of Salmonella Infections In Australia
Funder
National Health and Medical Research Council
Funding Amount
$763,447.00
Summary
Salmonella is a leading cause of the food-borne disease – salmonellosis. It is responsible for considerable morbidity and has an enormous economic cost. Molecular typing is the key to rapidly identify and control outbreaks. This project will optimise the use of whole genome sequencing for outbreak investigation and long term epidemiology. A surveillance system that integrates genome sequence and epidemiological data will be highly significant for outbreak investigation and disease prevention.
Improving The Understanding And Management Of Important Human Bacterial Infections
Funder
National Health and Medical Research Council
Funding Amount
$204,196.00
Summary
This project will focus on two important bacteria, Staphylococcus aureus (Golden Staph), and Enterococcus faecium, both causes of serious infections in hospital and community patients in Australia. Using new technologies, including whole genome sequencing, this project will lead to significant advances in understanding how these bacteria evolve, spread and cause disease. This will lead to new strategies for prevention and management of infections caused by these important bacteria.
Molecular Mechanisms Of Persistence Of Mycobacterium Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$398,142.00
Summary
Mycobacterium tuberculosis is the bacterium that causes tuberculosis (TB. It infects about third of all people in the world and kills several million people each year. People with active TB spread the mycobacteria in aerosols from their breath. When another person inhales an infected aerosol the mycobacteria enter their lungs and establish a new infection. During the course of infection M. tuberculosis is exposed to a variety of harsh environments inside the lungs which normally kill other bacte ....Mycobacterium tuberculosis is the bacterium that causes tuberculosis (TB. It infects about third of all people in the world and kills several million people each year. People with active TB spread the mycobacteria in aerosols from their breath. When another person inhales an infected aerosol the mycobacteria enter their lungs and establish a new infection. During the course of infection M. tuberculosis is exposed to a variety of harsh environments inside the lungs which normally kill other bacteria. M. tuberculosis is able to survive and adapt to those harsh environments. M. tuberculosis has an especially thick and tough cell wall which protects it. M. tuberculosis can adapt to the environments it encounters in a patient by changing their cell walls. The wall also protects mycobacteria from chemicals so it is resistant to many common antibiotics. There are some drugs to treat TB however M. tuberculosis is building up resistance to those drugs so we need to find new ones We will determine how mycobacteria synthesize their special cell wall and how they adapt during an infection. If we know how the details of how M. tuberculosis protects itself then we can find potential weakness which could be targets for the development of new drugs to treat TB.Read moreRead less
Acinetobacter Baumannii Virulence From A Regulatory Perspective: The Role Of Two Component Signal Transduction Systems
Funder
National Health and Medical Research Council
Funding Amount
$608,731.00
Summary
Acinetobacter baumannii is becoming a significant pathogen in the hospital and more recently in the community. It is very resistant to removal from surfaces and upon entering the host is almost impossible to treat with currently available antibiotics. It causes a wide range of disease states from wound infections and pneumonia to bacteraemia; little is known of this process. This research will increase our understanding of the disease process, providing possible treatment options in the future.
Manipulating Immunity To Mycobacterium Tuberculosis With Novel Vaccines And Immunotherapeutics
Funder
National Health and Medical Research Council
Funding Amount
$524,770.00
Summary
Tuberculosis (TB) is an enormous world health problem with 2 million deaths per year and an estimated one third of the world s population infected with the TB bacterium. People who become infected with the bacterium and cannot clear the infection are at great risk of developing TB later in life. Control of TB is confronted with two major problems. First, the only vaccine available for TB, known as BCG, is not very effective at preventing the disease. We do not know why BCG is not an effective va ....Tuberculosis (TB) is an enormous world health problem with 2 million deaths per year and an estimated one third of the world s population infected with the TB bacterium. People who become infected with the bacterium and cannot clear the infection are at great risk of developing TB later in life. Control of TB is confronted with two major problems. First, the only vaccine available for TB, known as BCG, is not very effective at preventing the disease. We do not know why BCG is not an effective vaccine and the type of immune response required to achieve optimal protection against TB is not fully understood. Second, the drugs currently used to treat TB are expensive, treatment times are long and drug resistance is increasing at an alarming rate. Therefore there is an urgent need to develop new vaccines and therapies against TB. We propose to use animal models of TB infection and sophisticated immunological techniques to compare immune responses generated by TB, BCG and new generation vaccines developed in our laboratory. This will allow us to identify the key features of a vaccine that results in effective, long-lasting protection against TB infection. Novel strategies to increase the immune response in the lung, the main site of TB infection, will also be examined. This will involve pulmonary delivery of molecules that increase the number and effectiveness of lung antigen presenting cells, which are necessary to drive the right type of immune response to eradicate the TB bacterium. Increasing lung immunity will be used to either boost the effect of the BCG vaccine, or as a therapy to kill the bacterium in those already infected. This is an internationally competitive project and our team is at the forefront of this research effort. The development of new vaccines to prevent TB or new strategies to treat established TB infection would be a major medical breakthrough and a represent a significant achievement for Australian health and medical research.Read moreRead less
Understanding Virulence Of Invasive Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$772,711.00
Summary
Staph aureus (Golden staph) is a major cause of disease in humans. In this project we will use state-of-the-art molecular biology and genomics to fully understand the mechanisms of virulence in this pathogen. This information will inform future approaches to development of therapeutics, as well as the use of genomics in clinical microbiology and disease management.
A One Health Approach To Assessing The Threat Of Clostridium Difficile To Australia’s Biosecurity: A Genomic Investigation Of Human, Animal And Environmental Isolates
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Clostridium difficile is a bacterium that causes life-threatening diarrhoea in humans and animals and is a major public health issue in Australia. This project will study the genetic make-up of the bacterium and identify factors contributing to the emergence, evolution, and spread of C. difficile. This knowledge will be essential in guiding effective public health interventions and reducing deaths from C. difficile infection in humans and animals.
Non-coding RNA Regulation Of Virulence In Enterohaemorrhagic E. Coli
Funder
National Health and Medical Research Council
Funding Amount
$389,313.00
Summary
Shiga toxins cause potentially fatal haemolytic uremic syndrome (HUS) and are transferred between bacterial pathogens by bacteriophage (bacterial viruses). We have recently found that the Shiga toxin encoding bacteriophage encodes an unusually large number of non-coding RNAs (RNA regulators of gene expression). This Project aims to understand how these RNA regulators benefit the Shiga toxin bacteriophage and use this knowledge to develop interventions that will prevent expression of the toxin.