Some of the world's most important diseases, including important diseases of indigenous chilren and the hospitalised elderly are caused by bacteria that carry a surface coating called a capsule. It is not clear how this capsule is retained by bacteria. Resolution of this question could lead to the development of new disinfectants that will stop hospital-acquired infections, to new reagents that can be incoporated into medical devices where bacteria frequently grow, and new antibiotics.
The Molecular Physiology Of Streptococcus Pneumoniae During Sepsis
Funder
National Health and Medical Research Council
Funding Amount
$232,504.00
Summary
The project will determine the way in which pneumococcus changes its properties when it invades the bloodstream of the human host. Since these changes are linked to sepsis then this new understanding will provide information that can be used to manage and control acute pneumococcal infection.
How A Multidrug Resistant Bacterial Pathogen Has Become Pandemic
Funder
National Health and Medical Research Council
Funding Amount
$1,116,544.00
Summary
The pandemic spread of antibiotic resistant E. coli ST131 is a major human health problem. ST131 is the globally dominant cause of urinary tract and bloodstream infections. This project will use advanced genetics and animal infection models to understand the features of ST131 that have fueled its global dominance. The outcomes will unravel the molecular mechanisms that enable ST131 to persist and cause repeat infection, and guide the development of new precision medicine therapeutics.
The Epidemiology And Treatment Of Infections Due To Multiresistant Gram Negative Bacteria
Funder
National Health and Medical Research Council
Funding Amount
$274,946.00
Summary
This fellowship application deals with the treatment of infections due to antibiotic resistant bacteria. The World Economic Forum recently discussed threats to our modern way of life. The highest ranked threats were climate change, terrorism and antibiotic resistance. During this Fellowship, two large clinical trials of treatment strategies for antibiotic resistant bacteria will be supervised by Professor Paterson.
BLING III: A Phase III Randomised Controlled Trial Of Continuous Beta-lactam Infusion Compared With Intermittent Beta-lactam Dosing In Critically Ill Patients
Funder
National Health and Medical Research Council
Funding Amount
$3,269,943.00
Summary
This Australian-led trial of global significance will provide definitive clinical evidence of the optimal method for treating patients with severe sepsis using beta-lactam antibiotics. The trial will compare whether continuous infusion of beta-lactam antibiotics improves outcomes for patients compared with standard intermittent dosing. The potential significance of this trial is that it may lead to a simple and cost-effective intervention to improve survival for patients with severe infections.
Inflammatory processes are normally regarded as being initiated and maintained through the activities of white blood cell macrophages. We propose to explore the role of lymphocyte delivery of protease molecules termed granzymes in inflammation. Our preliminary data has demonstrated a novel paradigm involving amplification of septic shock through the activity of granzymes. We now wish to exlore these interactions at a cellular and biochemical level as a means to better understand inflammation.
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
Contribution Of Dendritic Cell Paralysis To The Immunosuppression Associated With Systemic Infections
Funder
National Health and Medical Research Council
Funding Amount
$490,051.00
Summary
The immune system fights viruses and other infections mobilising antibody-producing B cells and killer T cells. The B cells and killer T cells are recruited by specialysed cell of the immune system called Dendritic Cells (DC). The DC are distributed all over the body, where they play an immunosurveillance role: they constantly monitor their sorroundings for the presence of pathogens. When DC detect these pathogens they become activated . They capture the pathogen, break it into small pieces call ....The immune system fights viruses and other infections mobilising antibody-producing B cells and killer T cells. The B cells and killer T cells are recruited by specialysed cell of the immune system called Dendritic Cells (DC). The DC are distributed all over the body, where they play an immunosurveillance role: they constantly monitor their sorroundings for the presence of pathogens. When DC detect these pathogens they become activated . They capture the pathogen, break it into small pieces called antigens, and display these antigens on their surface, where they can be seen by helper T cells, which in turn mobilise the B cells, and by killer T cells. This chain of reactions initiates an immune response. The DC undergo profound changes after they detect pathogens. They stop monitoring their sorroundings, and concentrate on displaying to T cells the antigens that belonged to the pathogen that triggered their initial activation. Indeed, they do not respond to new pathogen encounters. In normal conditions few DC are activated by each pathogen encounter, so there are always enough DC ready to respond to new infections. However, there are situation that activate nearly all the DC at the same time. This can happen during sepsis (bacterial infection of the blood) and malaria. It has been recognised for a long time that these two conditions can be immunosuppressive they shut-down the immune system. Our previous work has demonstrated that this is in part due to the excessive number of DC that sepsis or malaria activate, leaving no more DC capable of responding to subsequent infections. This work has focused on the immediate effects of sepsis or malaria -within the first 24 hours or so; now we want to investigate the efffect of these conditions on the reconstitution of the DC network. We think this will help us to find treatments to restore immunocompetence a functional immune system- in sepsis or malaria patients.Read moreRead less
This Fellowship will enable research into the basis for life-threatening infection in the critically ill, including severe pneumonia, septic shock and the complexities of antibiotic resistance in bacteria, as well as the translation of this research into practice (including rapid diagnostics).
Copper And Its Antibacterial Action: An Emerging Aspect Of Host Defence Against Bacterial Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$454,858.00
Summary
This project will determine the way in which copper is used as an antimicrobial agent to kill Salmonella that reside inside the macrophage (white blood cell) of the host and also determine how Salmonella defends against copper-dependent killing. It will also determine the role of copper in the killing of extra-intestinal pathogens during sepsis. These results will provide information that can be used to manage and control infections intracellular and extracellular bacterial pathogens.