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
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.
Genome Wide Investigations Of Mycobacterium Tuberculosis To Reveal Processes Of Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$396,341.00
Summary
Tuberculosis remains a global health burden of staggering proportions. Around 1 in 3 people are infected with Mycobacteria tuberculosis, the organism responsible for the disease, which kills 2 million people annually. The emergence of strains now resistant to almost all of our front line drugs has placed extra pressure on researchers who are attempting to develop new protective vaccines and the critical antibiotics required to eradicate the disease. Furthermore the current global HIV pandemic is ....Tuberculosis remains a global health burden of staggering proportions. Around 1 in 3 people are infected with Mycobacteria tuberculosis, the organism responsible for the disease, which kills 2 million people annually. The emergence of strains now resistant to almost all of our front line drugs has placed extra pressure on researchers who are attempting to develop new protective vaccines and the critical antibiotics required to eradicate the disease. Furthermore the current global HIV pandemic is making the situation far worse as HIV kills the very cells of the body that protect us from tuberculosis. This research project will fill the significant gaps in our knowledge of M. tuberculosis infection, specifically identify the genes of the organism which allow it to invade and spread throughout the body. M. tuberculosis infection consists of 3 characteristic stages, i.e. colonisation, spread and long term survival in specialised structures called granulomas. It is from these granulomas that the bacterium can emerge after long periods of inactivity to cause clinical tuberculosis. Using a mouse model of infection I will define the genes needed by the bacterium to survive at these 3 key stages of disease thereby providing for a better knowledge base from which to design new vaccine strategies and to create effective drugs.Read moreRead less
Evolution And Pathogenicity Of NDM-1 Positive Escherichia Coli
Funder
National Health and Medical Research Council
Funding Amount
$643,275.00
Summary
Antibiotic resistance (AR), as highlighted by the WHO, is the most pressing medical need of the 21C – some infections are now untreatable. Our research will focus on the new "superbug" NDM-1 positive E. coli. We will correlate AR and pathogenicity and explore the evolution of these "superbugs" using state-of-the-art sequencing. This research will benefit Australian medicine by predicting timelines of AR epidemics and by conducting the first analyses on the virulence potential of these strains.
Using Genetic Tools To Study Helicobacter Pylori Pathogenesis And Persistence
Funder
National Health and Medical Research Council
Funding Amount
$316,449.00
Summary
H. pylori infection is the leading cause of gastric ulcer disease and stomach cancer. In light of emerging antibiotic resistance and failed vaccine trials, alternative therapies are needed to treat this lifelong infection. This project aims to develop tools to identify and characterize genes required by H. pylori for infection which will serve as new drug targets. This new knowledge will also contribute to a better understanding of the persistence of this and other bacteria.
Defining Pathogenic Mechanisms Of Intracellular Bacteria
Funder
National Health and Medical Research Council
Funding Amount
$494,691.00
Summary
This study explores how the bacterium Coxiella burnetii causes the serious infectious disease Q fever. Coxiella is a potential biological weapon because it is very stable in the environment and few organisms are required to cause disease. Coxiella is able to commandeer human cells to replicate in a specialized vacuole but little is understood about how they do this. We will examine the virulence factors of Coxiella and investigate how they allow the bacteria to replicate inside human cells.
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.
Comparative And Functional Genomics Of Human Bacterial Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$601,484.00
Summary
Bacteria have evolved different ways of causing disease in humans. Some bacteria produce toxins that attack the host or they have developed ways to persist in the host by evading immune responses and resisting antibiotics. This project is concerned with understanding how these processes occur and developing preventative strategies for two important groups of bacteria that cause disease in humans, including the bacteria that cause TB and the devastating skin disease Buruli ulcer, and the hospital ....Bacteria have evolved different ways of causing disease in humans. Some bacteria produce toxins that attack the host or they have developed ways to persist in the host by evading immune responses and resisting antibiotics. This project is concerned with understanding how these processes occur and developing preventative strategies for two important groups of bacteria that cause disease in humans, including the bacteria that cause TB and the devastating skin disease Buruli ulcer, and the hospital superbug "Golden Staph".Read moreRead less
Characterizing The Molecular Mechanisms Of Clinically Important Bacterial-fungal Interactions; The Potential To Uncover Novel Therapeutic Targets
Funder
National Health and Medical Research Council
Funding Amount
$480,492.00
Summary
In hospitals and in nature, diverse microbes, such as bacteria and fungi, often live in close proximity to each other. Their interactions can either be helpful or detrimental to one another, and such interactions are likely important for their ability to cause human disease. This proposal aims to study the mechanisms by which bacteria interact with fungi and by doing so, will identify important mechanisms of how microbes cause human illness and also uncover new targets for antibiotic development ....In hospitals and in nature, diverse microbes, such as bacteria and fungi, often live in close proximity to each other. Their interactions can either be helpful or detrimental to one another, and such interactions are likely important for their ability to cause human disease. This proposal aims to study the mechanisms by which bacteria interact with fungi and by doing so, will identify important mechanisms of how microbes cause human illness and also uncover new targets for antibiotic development.Read moreRead less
The Pathogenesis Of Melioidosis: The Interaction Of Burkholderia Pseudomallei With Host Cells.
Funder
National Health and Medical Research Council
Funding Amount
$344,375.00
Summary
Melioidosis is an often fatal disease of mainly tropical Australia and SE Asia caused by a bacterium which is found in soil and water. Infection occurs via wounds or by inhalation. Melioidosis has recently become endemic in south-west Western Australia and south-eastern Queensland, and could represent an emerging disease worldwide. Melioidosis disproportionately affects Aboriginal Australians. Melioidosis has many forms including septicemia with damage to most organs, particularly lung, spleen a ....Melioidosis is an often fatal disease of mainly tropical Australia and SE Asia caused by a bacterium which is found in soil and water. Infection occurs via wounds or by inhalation. Melioidosis has recently become endemic in south-west Western Australia and south-eastern Queensland, and could represent an emerging disease worldwide. Melioidosis disproportionately affects Aboriginal Australians. Melioidosis has many forms including septicemia with damage to most organs, particularly lung, spleen and liver, acute localised suppurative infection and pneumonia. Melioidosis may also become latent, and later develop into an acute and fatal infection. It is important to understand, at the molecular level, how and why the causative bacterium is able to cause disease. Only with such an understanding can measures be undertaken to prevent the disease, or novel methods developed to control the disease. Colonisation of a host is a first step in the disease process for all bacteria which cause disease. Large protein molecules located on the surface of disease-causing bacteria are usually neccessary for colonisation of the host since they allow adherence to the surface of host cells. We have previously undertaken a basic study of adherence. This study will build on this research with the aim of identifying molecules which mediate adherence to host cells, using in vivo and in vitro methods, including the techniques of molecular biology. This study will inevitably lead to the development of vaccine candidates which is important to the management of melioidosis, particularly in high risk groups. It may also allow the development of novel antimicrobial compounds.Read moreRead less