Novel Perspectives On The Function Of AB5 Toxin B Subunits
Funder
National Health and Medical Research Council
Funding Amount
$1,041,896.00
Summary
AB5 toxins are important virulence factors of pathogenic bacteria. They comprise pentameric B subunits that bind to target cell surfaces and catalytic A subunits that damage host cell functions. This proposal examines a new paradigm wherein the B subunits are significant contributors to cell damage. We will characterize the cytopathic properties of diverse B subunits, particularly those of emerging toxins. This will provide novel insights into pathogenesis and inform development of therapeutics.
Helicobacter Pylori VacA Toxin: Modulation Of Human Mitochondrial Function By A Bacterial Pathogen
Funder
National Health and Medical Research Council
Funding Amount
$508,003.00
Summary
This work will greatly further our understanding of how a bacterium, Helicobacter pylori, causes stomach ulcers and cancer. We will use cutting edge model systems to study the VacA toxin that is secreted from the bacteria and is targeted to human cells. We will examine where the toxin goes and how it affects our cells. It is expected that the improved understanding that will arise from this work will assist researchers to better devise drugs against this prevalent pathogen.
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.
The Impact Of Clostridium Difficile Infection And The Host Immune Response On Colonic Homeostasis And Regeneration.
Funder
National Health and Medical Research Council
Funding Amount
$932,212.00
Summary
Hospital-acquired infections with the bacterium Clostridium difficile are a major global public health concern with highly virulent isolates emerging overseas in 2002 and in Australia in 2010. These have spread through our hospitals and are also found in the community. This project will increase our understanding of how these strains cause severe gut disease, which is critical for the development of improved strategies for preventing and treating these infections and reducing antibiotic use.
Targeting Glycointeractions To Generate New Opportunities To Treat And Prevent Bacterial Infections.
Funder
National Health and Medical Research Council
Funding Amount
$774,540.00
Summary
Bacteria and bacterial toxins can interact with complex sugar structures on human cells called glycans. My research team has identified new and important glycan interactions used by bacteria that cause diseases ranging from pneumonia, meningitis and food borne infections to urinary tract and sexually transmitted diseases. Now that these interactions have been discovered, they can be exploited to create drugs and vaccines that may treat and prevent disease by blocking the glycan interactions.
Structure And Functional Characterisation Of AB5 Toxins
Funder
National Health and Medical Research Council
Funding Amount
$574,890.00
Summary
The proposed research program, using a combination of structure and biochemical analyses, will provide insight into two novel AB5 toxins that represent a medically important family of proteins. This study will not only improve our fundamental understanding of AB5 toxins action but could lead to rational design of antimicrobials.
Expression And Secretion Of Large Clostridial Toxins From The Pathogenic Clostridia.
Funder
National Health and Medical Research Council
Funding Amount
$332,258.00
Summary
The large clostridial toxins are an important family of bacterial virulence factors that includes toxins from many disease-causing clostridial species. Despite their impact on public health, pathogenesis of disease caused by these bacteria is poorly understood. We will analyse how these bacteria regulate the production and secretion of the large toxins, which will give us a better understanding of the mechanisms of disease causation as well as identifying novel common therapeutic targets.
The Role Of Clostridium Difficile Virulence Factors In Mediating The Host-pathogen Interactions That Lead To Gastrointestinal Disease
Funder
National Health and Medical Research Council
Funding Amount
$444,351.00
Summary
Hospital-acquired infections with the bacterium Clostridium difficile are a major global public health concern with more virulent isolates emerging overseas since 2000. These strains were detected in Australia in 2010 and are now spreading throughout our hospitals. This project will increase our understanding of how these strains cause disease and why they are more harmful, which is critical for the development of improved strategies for preventing and treating these infections.
Novel Therapeutic And Preventive Strategies For Clostridium Difficile Infections.
Funder
National Health and Medical Research Council
Funding Amount
$508,556.00
Summary
The bacterium Clostridium difficile is the major cause of nosocomial diarrhoea in many countries, including Australia. More virulent isolates have recently emerged, leading to increased incidence and disease severity in many countries. This project will make a major contribution to our understanding of how these bacteria cause disease. Preventive or treatment measures based on these research findings will help to prevent or lessen the severity of any epidemics that occur in Australia.
Pathogenesis, Treatment And Prevention Of Bacterial Infectious Diseases
Funder
National Health and Medical Research Council
Funding Amount
$852,458.00
Summary
Bacterial infectious diseases remain a serious threat to human health, accounting for over 10 million deaths each year. My research program aims to better understand the dynamic interactions between major disease-causing bacteria and their human hosts, and to directly apply this new knowledge to the development of improved vaccines and novel treatment strategies. These are urgently needed to combat bacterial infectious diseases in the 21st century.