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.
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.
Molecular Basis Of O-antigen Modification And Genomics Of Serotype-converting Bacteriophages Of Shigella Flexneri
Funder
National Health and Medical Research Council
Funding Amount
$268,264.00
Summary
There are approximately 165 million cases of shigellosis world wide annually, resulting in 1.1 million deaths. The majority of cases occur in developing countries and most deaths occur in children under 5 years of age. Shigellosis is mainly caused by the bacterium Shigella flexneri. There are 13 different serotypes of S. flexneri determined by bacterial cell-surface polysaccharides called O-antigens. Bacterial viruses (bacteriophages) carry the genes which confer O-antigen variation. Infection a ....There are approximately 165 million cases of shigellosis world wide annually, resulting in 1.1 million deaths. The majority of cases occur in developing countries and most deaths occur in children under 5 years of age. Shigellosis is mainly caused by the bacterium Shigella flexneri. There are 13 different serotypes of S. flexneri determined by bacterial cell-surface polysaccharides called O-antigens. Bacterial viruses (bacteriophages) carry the genes which confer O-antigen variation. Infection and subsequent incorporation of the virus into the genetic material of the bacterial cell result in modification of the bacterial O-antigen. This phage-mediated O-antigen modification gives rise to different serotypes. The project will address fundamental processes related to the O-antigen modification. This will be achieved by studying structure and function of the enzymes encoded by the O-antigen modification gene cluster. We have isolated several serotype-converting bacteriophages from S. flexneri and we plan to compare and characterise their genomic information to increase understanding of their origin and relationship with the bacterial host.Read moreRead less
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.
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
Non-coding RNA Regulation Of Virulence In Enterohaemorrhagic E. Coli
Funder
National Health and Medical Research Council
Funding Amount
$389,313.00
Summary
Shiga toxins cause potentially fatal haemolytic uremic syndrome (HUS) and are transferred between bacterial pathogens by bacteriophage (bacterial viruses). We have recently found that the Shiga toxin encoding bacteriophage encodes an unusually large number of non-coding RNAs (RNA regulators of gene expression). This Project aims to understand how these RNA regulators benefit the Shiga toxin bacteriophage and use this knowledge to develop interventions that will prevent expression of the toxin.
Urinary Tract E. Coli: The Good Guys Versus The Bad Guys
Funder
National Health and Medical Research Council
Funding Amount
$296,150.00
Summary
Escherichia coli is the primary cause of urinary tract infection (UTI) in the developed world. In Australia alone, E. coli affects more than 250,000 yearly to the extent where they require medical intervention. It is estimated that one in four women and one in twenty men will develop a UTI in their lifetime and in the USA UTIs result in $1.6 billion in medical expenses each year. Uropathogenic E. coli (UPEC) strains readily form biofilms on indwelling catheters and recent evidence suggests that ....Escherichia coli is the primary cause of urinary tract infection (UTI) in the developed world. In Australia alone, E. coli affects more than 250,000 yearly to the extent where they require medical intervention. It is estimated that one in four women and one in twenty men will develop a UTI in their lifetime and in the USA UTIs result in $1.6 billion in medical expenses each year. Uropathogenic E. coli (UPEC) strains readily form biofilms on indwelling catheters and recent evidence suggests that they also form biofilm-like aggregates in the bladder. No treatment other than antibiotics (often inefficient due to resistance) is currently available. E. coli is also the most frequent cause of asymptomatic bacteriuria (ABU). ABU occurs in up to 6% of healthy individuals and affects high risk groups such as the elderly and diabetics. In general, most patients with ABU do not need treatment and in many cases the colonizing organism actually helps to prevent infection by other more virulent bacteria. The aim of this project is to compare UPEC and ABU E. coli for differences associated with virulence and biofilm growth. The project will generate a comprehensive and defined strain bank relative to E. coli that cause UTI. Understanding biofilm growth by this organism may lead to the development of improved and-or novel treatments. Furthermore, increased knowledge of ABU E. coli is essential if we are to fully explore the possibility of employing these organisms as probiotic agents to prevent infection by other pathogens in specific high risk patient groups.Read moreRead less
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 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.
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.