The Role Of Clostridium Difficile Spore Interactions With The Host In Gastrointestinal Infection And Disease
Funder
National Health and Medical Research Council
Funding Amount
$511,467.00
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.
Is Mycobacterium Ulcerans A Zoonotic Agent Spread By Mosquitoes?
Funder
National Health and Medical Research Council
Funding Amount
$335,853.00
Summary
Last year record numbers of a mysterious flesh-eating bacterial disease called Buruli ulcer were reported in Australia. Wild animals such as possums and rats harbour the bacteria in their guts but we don't know how the disease is transmitted to humans. In this project we will work out how the bacteria survives in the guts of animals and how people contract Buruli ulcer. With this information we can stop the spread of this debilitating disease.
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.
Characterising The Role Of IL-37 In The Development Of H. Pylori Infection.
Funder
National Health and Medical Research Council
Funding Amount
$641,992.00
Summary
H. pylori infects more than 50% of the worlds population and is the causative agent of gastric cancer, the second leading cause of cancer-related deaths worldwide. Infection with H. pylori occurs during early childhood and persists within the host for life, causing immune suppression and therefore preventing clearance of the infection from the individual. We will examine a newly identified mechanism of H. pylori-induced immune suppression in humans in an attempt to provide novel treatments.
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.
Integrated Bacterial Genomics And Virulence Analysis Of Uropathogenic Streptococcus Agalactiae
Funder
National Health and Medical Research Council
Funding Amount
$747,457.00
Summary
Urinary tract infections (UTI), which start as a bladder infection and often evolve to encompass the kidneys, are among the most common infectious diseases in humans. Streptococcus agalactiae is an important cause of gram-positive bacterial UTI. We will study the genomes and functions of specific genes in reference strains of this bacterium isolated from patients with different forms of infection to elucidate how bacterial genes and virulence factors contribute to these types of infections.
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.
Capsule Synthesis And Tyrosine Phosphorylation In Streptococcus Pneumoniae
Funder
National Health and Medical Research Council
Funding Amount
$587,803.00
Summary
The bacterium Streptococcus pneumoniae causes much morbidity and mortality worldwide. Antibiotic resistance and vaccination is problematic. New anti-infectives are required. We will study proteins (CpsB, CpsC, CpsD) that regulate polysaccharide capsule synthesis to understand their interactions, and to identify drugs that inhibit CpsB and CpsD. We will also investigate the wider role of tyrosine phosphorylation in the bacterium and investigate how this intersects with capsule synthesis.
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.
Structural And Functional Analysis Of Glucosyltransferases (Gtr) Involved In O-antigen Modification Of Shigella Flexneri
Funder
National Health and Medical Research Council
Funding Amount
$340,976.00
Summary
Shigellosis caused by Shigella flexneri is a medically significant disease in developing countries. Serotypes of S. flexneri are determined by bacterial cell-surface polysaccharides called O-antigens. Bacterial viruses carry the genes which confer O-antigen modification giving rise to different serotypes. The project will address fundamental processes related to the O-antigen modification by studying structure and function of the enzymes encoded by the O-antigen modification gene cluster.