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Virulence Mechanisms In Hypervirulent Epidemic Strains Of Clostridium Difficile.
Funder
National Health and Medical Research Council
Funding Amount
$499,135.00
Summary
The bacterium Clostridium difficile is the major cause of nosocomial diarrhoea in many countries, including Australia. More virulent isolates have emerged since 2000, leading to increased incidence and severity of disease in many countries and resulting in epidemics. This project will make a major contribution to our understanding of how these bacteria cause disease and may help to prevent outbreaks of the hypervirulent strains in Australia by identifying potential new vaccine candidates.
Role Of Protease Activated Receptors Type 2 (PAR2) During Inflammation Of Airways And Intestine
Funder
National Health and Medical Research Council
Funding Amount
$235,500.00
Summary
Epithelial cells lining the airways and the intestine contain receptors that are activated by proteases, which are protein cleaving enzymes. Activation of the subtype 2 of these receptors (PAR2) has been shown to cause salt and water transport in intestinal cells in culture. Little is known about the effects of PAR2-activation in the native airways and intestinal tissues. These tissues will be studied in the present project. A large increase in PAR2 is found in various diseases which are paralle ....Epithelial cells lining the airways and the intestine contain receptors that are activated by proteases, which are protein cleaving enzymes. Activation of the subtype 2 of these receptors (PAR2) has been shown to cause salt and water transport in intestinal cells in culture. Little is known about the effects of PAR2-activation in the native airways and intestinal tissues. These tissues will be studied in the present project. A large increase in PAR2 is found in various diseases which are paralleled by a strong inflammation. Thus, PAR2 is likely to play a central role in intestinal diseases such as acute infectious diarrhea and chronic inflammatory bowel disease. PAR2 may also participate in the severe diarrhea frequently observed in patients with intestinal tumors. Similarly, inflammatory mediators released during airway infections are likely to act on PAR2, causing inappropriate secretion and a running nose. Most importantly, PAR2 are found in large excess in the airways of asthma patients. Since nothing is known about the impact of these receptors on fluid and electrolyte transport in the airways it appears timely and highly relevant to study the function of PAR2 in the airway epithelium. We will assess PAR2 mediated responses in human nasal biopsies. A more detailed analysis of the intracellular processes will be done in mouse trachea. We will further study the function of PAR2 in the intestinal epithelium. Activation of the ion transport via PAR2 will be examined in the mouse distal colon and in human rectal biopsies. We will utilize techniques such as Ussing chamber and patch clamp recordings to analyze the transport processes. The results should gain new inside into the role of PAR2 during inflammatory diseases of the airways and the intestine such as asthma and chronic inflammatory bowel diseases.Read moreRead less
Multiple Antibiotic Resistance In An Acinetobacter Baumannii Global Clone
Funder
National Health and Medical Research Council
Funding Amount
$606,580.00
Summary
Antibiotic resistant bacteria that cause infections in hospitals can originate anywhere, then spread world wide. They start off resistant to a few antibiotics, then become resistant to new antibiotics that are introduced to treat them. This project will investigate how resistance to antibiotics was acquired by Acinetobacter baumannii which is now resistant to most antibiotics, and why the old resistance genes are not being lost. This will help track these bacteria moving into and around Australi ....Antibiotic resistant bacteria that cause infections in hospitals can originate anywhere, then spread world wide. They start off resistant to a few antibiotics, then become resistant to new antibiotics that are introduced to treat them. This project will investigate how resistance to antibiotics was acquired by Acinetobacter baumannii which is now resistant to most antibiotics, and why the old resistance genes are not being lost. This will help track these bacteria moving into and around Australia.Read moreRead less
Genetic Determinants Of Interleukin-10 Response After Infectious Stimuli
Funder
National Health and Medical Research Council
Funding Amount
$276,000.00
Summary
Interleukin-10 is a key protein in the immune defense against infection, being the principal brake for the immune response. An diminished production of interleukin-10 has been implicated as a major cause of a number of devestating medical conditions including septic shock and acute respiratory distress syndrome. An excessive production of interleukin-10 may also be very harmful, and may be the primary cause of the reduction in immune function in many critically ill patients that leads to hospita ....Interleukin-10 is a key protein in the immune defense against infection, being the principal brake for the immune response. An diminished production of interleukin-10 has been implicated as a major cause of a number of devestating medical conditions including septic shock and acute respiratory distress syndrome. An excessive production of interleukin-10 may also be very harmful, and may be the primary cause of the reduction in immune function in many critically ill patients that leads to hospital acquired infections. These potential key roles of interleukin-10 in seriously ill patients makes it an attractive candidate to target for immune therapies. However, past experience with trials of immune-based therapies such as tumor necrosis factor alpha have taught us that we need to be much better at predicting individual immune responses if we are to 'interfere' with the immune system successfully. In the case of interleukin-10 there is substantial individual variation in the amount produced, with studies suggesting up to 70% of this variation is due to genetic differences. This project will establish the basis for this genetic variation by identiying both the genetic markers of high and low interleukin-10 response and the mechanisms by which these genetic markers change interleukin-10 production. This information will not only enable us to better target patients who may need an 'adjustment' of their immune function, but may also lead to novel therapeutic targets or therapeutic agents.Read moreRead less
Genomic Approaches To Understand And Control The Emergence Of Vancomycin Resistant Enterococcus Faecium (VREfm) In Australia.
Funder
National Health and Medical Research Council
Funding Amount
$756,163.00
Summary
VRE is a serious hospital superbug that has been increasing in many major hospitals around Australia, while at the same time MRSA (Golden Staph) infections have been decreasing. This project will find out why VRE is increasing by examining what happens to patients at a major Australian hospital from their time of admission to the onset of infection with VRE. At the end of the project we will have the first real understanding of how VRE is transmitted so we can develop effective infection control ....VRE is a serious hospital superbug that has been increasing in many major hospitals around Australia, while at the same time MRSA (Golden Staph) infections have been decreasing. This project will find out why VRE is increasing by examining what happens to patients at a major Australian hospital from their time of admission to the onset of infection with VRE. At the end of the project we will have the first real understanding of how VRE is transmitted so we can develop effective infection control measures.Read moreRead less
Harnessing The Type VI Secretion System ‘combat’ Arsenal Of A. Baumannii As A Source Of New Antimicrobials And Antimicrobial Targets
Funder
National Health and Medical Research Council
Funding Amount
$521,557.00
Summary
Infections caused by drug-resistant bacteria represent one of the greatest threats to human health. There is an urgent need to develop novel drugs and treatment strategies to combat infections by these drug-resistant organisms. We have shown that the bacteria A. baumannii uses a needle-like system to deliver lethal toxins into competitors. We will characterize these toxins so that we can manipulate them as weapons for controlling infections with multi-drug resistant bacteria.
Pathways To Extensive And Pan Antibiotic Resistance In The Globally Disseminated Acinetobacter Baumannii GC2 Clone
Funder
National Health and Medical Research Council
Funding Amount
$865,004.00
Summary
The project will study the evolution of a Acinetobacter baumannii clone that is found all around the world, and has become resistant to most or all of the currently available antibiotics. Resistance has been acquired in a series of steps, and the resistance genes present and the events involved will be used to understand the globalization process. The increased understanding of resistance development should assist in controlling untreatable infections and in preserving antibiotics.