Enhancing Host Defence Mechanisms In Severe Bacterial Infections
Funder
National Health and Medical Research Council
Funding Amount
$830,447.00
Summary
New options to treat bacterial infections are needed because of the rapid increase in antibiotic resistance. One very attractive strategy is to boost the body’s own defence mechanisms against bacteria. This project defines novel molecular mechanisms that can be manipulated to better control a bacterial infection. Novel drugs targeting these molecular pathways are already being developed, albeit for cancer. This project will help assess if these drugs may be useful to treat infections.
Dissecting Immune Responses To Salmonella Infection
Funder
National Health and Medical Research Council
Funding Amount
$415,797.00
Summary
Successful treatment of Salmonella infections requires a detailed understanding how Salmonella growth is controlled. This project will examine the role of white blood cells, will reveal how they contribute to the control of Salmonella infections and will test novel treatment options. The outcome of this project will significantly advance our understanding of immune responses against Salmonella.
Host Cell Death Signaling And Susceptibility To Bacterial Gut Infection
Funder
National Health and Medical Research Council
Funding Amount
$682,321.00
Summary
Bacterial infections are a major cause of infectious disease worldwide. Here we aim to characterise immune responses that help fight infection by E. coli and Salmonella. These bacteria have evolved ways to shut down many of our immune responses during infection, allowing them to survive and cause disease. This work will help understand the complex relationship between gut bacteria and our immune system and provide solutions for controlling infection and treating immune disorders of the gut.
Role Of Hypoxia Inducible Factor In Innate Immune Function Against Gram-positive Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$241,352.00
Summary
Our society is currently facing the rise of drug-resistant pathogens ("superbugs") such as the potentially devastating methicillin-resistant Staphylococcus aureus, or _MRSA�. Recently, a molecule known as HIF has been shown to control the ability of our white blood cells to kill bacteria. This proposal aims to investigate the use of HIF boosting drugs to treat infections. These novel HIF agonists could be used alongside conventional antibiotics to improve infectious disease.
Iron, Pseudomonas Aeruginosa And Lung Disease In Cystic Fibrosis.
Funder
National Health and Medical Research Council
Funding Amount
$322,875.00
Summary
Cystic fibrosis (CF) is the most common lethal geneticdisease in Caucasians. The worldwide incidence of the disorder is approximately 1 in 2,500 live births. The most significant clinical manifestation of CF is chronic lung infection, particularly with the bacterium, Pseudomonas aeruginosa. Even with the current aggressive antibiotic treatment regimens most patients ultimately succumb to infection with this organism and die before they reach 40 years-of-age. The overall aim of our work is to inc ....Cystic fibrosis (CF) is the most common lethal geneticdisease in Caucasians. The worldwide incidence of the disorder is approximately 1 in 2,500 live births. The most significant clinical manifestation of CF is chronic lung infection, particularly with the bacterium, Pseudomonas aeruginosa. Even with the current aggressive antibiotic treatment regimens most patients ultimately succumb to infection with this organism and die before they reach 40 years-of-age. The overall aim of our work is to increase the understanding of how P. aeruginosa persists in the CF lung, with the goal of developing more effective therapeutic strategies to eliminate chronic infection with this bacterium. The new perception is that P. aeruginosa bacteria flourish in mucus with a low oxygen content within the CF lung and persist despite aggressive antibiotic therapy because they have adopted an antibiotic-resistant, biofilm mode of growth. This has opened up exciting directions for new therapeutic strategies. Factors in CF mucus that regulate this mode of bacterial growth are potential targets for intervention. Our past work has shown that iron is likely to be one such factor. In this study, we will extend these findings and determine whether using iron-binding chemicals can disrupt these biofims and allow the host immune system and antibiotics to work more efficiently to kill the bacteria. Not only will this study provide further insights into the pathogenesis of P. aeruginosa in CF and the role of iron, but ultimately it will contribute to the improved treatment and prevention of chronic infection with this organism.Read moreRead less
Impact Of Influenza A Infection On T Cell-mediated Immunity To Pulmonary Tuberculosis.
Funder
National Health and Medical Research Council
Funding Amount
$488,058.00
Summary
Tuberculosis is a leading cause of death worldwide and there is an urgent need to develop better anti-TB vaccines. Infection with respiratory viruses may reduce memory T cell responses to M. tuberculosis (Mtb). This project will investigate if Influenza A infection reduces memory anti-tuberculosis T cell responses in mice previously exposed to Mtb or BCG. We will then use influenza viruses engineered to carry parts of Mtb proteins to boost anti-Mtb T cell responses and the protective effect of B ....Tuberculosis is a leading cause of death worldwide and there is an urgent need to develop better anti-TB vaccines. Infection with respiratory viruses may reduce memory T cell responses to M. tuberculosis (Mtb). This project will investigate if Influenza A infection reduces memory anti-tuberculosis T cell responses in mice previously exposed to Mtb or BCG. We will then use influenza viruses engineered to carry parts of Mtb proteins to boost anti-Mtb T cell responses and the protective effect of BCG.Read moreRead less
Understanding The Complex Relationship Between Host, Pathogen And Antibiotic Factors On Treatment Outcome In Serious Bacterial Infections
Funder
National Health and Medical Research Council
Funding Amount
$380,945.00
Summary
Millions of people still die every year from bacterial infections despite the availability of antibiotics. The same bacterial infection in one person can behave very differently in another person, so infections can range from trivial to life-threatening or fatal. Understanding the relationship between the patient, the infecting bacteria and the antibiotic treatment given will ultimately help to predict and improve outcomes for patients with serious bacterial infections.
The Team brings together a unique grouping of people with backgrounds in molecular biology, medical microbiology, microbiology, marine ecology and immunology to tackle a significant health problem infections caused by bacteria. Using a novel approach, based on understanding how marine organisms specifically interfere with bacterial colonisation, the Team over the past seven years has identified a group of compounds that represent a novel group of antibiotics. Publications and patenting by the Te ....The Team brings together a unique grouping of people with backgrounds in molecular biology, medical microbiology, microbiology, marine ecology and immunology to tackle a significant health problem infections caused by bacteria. Using a novel approach, based on understanding how marine organisms specifically interfere with bacterial colonisation, the Team over the past seven years has identified a group of compounds that represent a novel group of antibiotics. Publications and patenting by the Team has demonstrated that the Team is at the forefront of research in this area. The novel antibiotics work by preventing bacteria sticking to surfaces and by preventing the bacteria from releasing toxins. The studies will concentrate on those bacteria that produce infections in the lungs (acute pneumonia), eyes (corneal infection), ear (middle ear disease), and abscesses.Read moreRead less
The Effect Of Defective Iron Handling On Immune Function And Pseudomonas Aeruginosa Infection In The Cystic Fibrosis Lung
Funder
National Health and Medical Research Council
Funding Amount
$97,213.00
Summary
In this research higher degree I will study the effects of iron on airway sepsis in cystic fibrosis (CF), with a particular focus on the major pathogen Pseudomonas aeruginosa. Increased concentrations of iron have been described in the CF lung, and CF airway epithelial cells display abnormal iron handling which facilitates P. aeruginosa growth. I will explore imposed iron limitation combined with conventional antibiotics as a new therapeutic strategy for treatment of chronic airway infection.
Host-pathogen Interactions In Clostridial Myonecrosis
Funder
National Health and Medical Research Council
Funding Amount
$577,573.00
Summary
We will analyse the interaction between the bacteria that cause gas gangrene, and the infected host, from both a host and pathogen perspective. We will examine how the host’s response to infection can be modulated to decrease the severity of disease and we will identify the biochemical processes that are essential for bacterial growth in the host, a necessary prerequisite for disease. Outcomes will be a better understanding of the mechanisms of disease causation and improved disease control.