Recombinant Bacteria Expressing Oligosaccharide Receptor Mimics For Prevention Of Enteric Infections
Funder
National Health and Medical Research Council
Funding Amount
$451,056.00
Summary
Gastrointestinal infectious diseases kill more than 3 million people each year. The principal microbial pathogens responsible for these infections are known to exploit oligosaccharides on the surface of host cells as receptors for ahesins or toxins. We have developed (and patented) a novel anti-infective strategy, based on mimicry of oligosaccharide receptors for toxins and adhesins produced by enteric pathogens on the surface of harmless carrier bacteria. Oral administration of such recombinant ....Gastrointestinal infectious diseases kill more than 3 million people each year. The principal microbial pathogens responsible for these infections are known to exploit oligosaccharides on the surface of host cells as receptors for ahesins or toxins. We have developed (and patented) a novel anti-infective strategy, based on mimicry of oligosaccharide receptors for toxins and adhesins produced by enteric pathogens on the surface of harmless carrier bacteria. Oral administration of such recombinant probiotics has the potential to prevent enteric infections by binding and neutralizing toxins in the gut lumen and by blocking adherence of the pathogen to intestinal epithelial cells. As a prototypic example, we have developed a bacterium capable of preventing the serious consequences of Shiga toxigenic Escherichia coli (STEC) infections; this agent binds Shiga toxin with very high efficiency and is 100% protective in animal models. The strategy has very broad applications, however, and receptors for virtually any pathogen can be mimicked by expression of appropriate glycosyl transferases in a suitable harmless host bacterium. This proposal involves extension of our existing work to develop therapeutic agents for other important life threatening diarrhoeal diseases including cholera, travellers' diarrhoea, dysentery, antibiotic-associated colitis, rotavirus, etc.Read moreRead less
Enhancing Control Of Enteric Bacteria Through Pathogen Genomics
Funder
National Health and Medical Research Council
Funding Amount
$645,205.00
Summary
Bacteria part of the Enterobacteriaceae family are responsible for causing significant enteric disease in Australia and internationally. Compounding the public health threat posed by these enteric bacteria is the rise in antimicrobial resistance, which limits treatment options. This project has three complementary research objectives; 1) to investigate new control strategies; 2) to better understand outbreak dynamics and; 3) to explore how bacteria are causing new disease in humans.
Role Of Microbiota In The Developing Enteric Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$661,979.00
Summary
The correct development of neurons in the gut is vital for digestive functions. This project will provide novel insights into how environmental factors such as the bacteria that reside in the gut and changes in diet affect maturation of the gut’s nervous system. The data will improve knowledge of the effects of widely used antibiotics and probiotics, which will facilitate strategies to improve human health and quality of life.
Understanding The Disease Burden And Antibiotic Resistance In Patients With Bloodstream Infections Caused By Enterobacteriaceae In Australia
Funder
National Health and Medical Research Council
Funding Amount
$135,285.00
Summary
This study aims to establish the epidemiology of bloodstream infections caused by Enterobacteriaceae (enteric or gut bacteria) in Australia, by examining infection rates, types of antibiotic resistance present, and which treatments optimise clinical outcomes.
Interactions Between Host And The Gut Microbiome In The Pathogenesis Of Ankylosing Spondylitis And Crohn's Disease
Funder
National Health and Medical Research Council
Funding Amount
$572,227.00
Summary
Ankylosing spondylitis (AS) and Crohn's disease (CD) are common immune-mediated diseases affecting primarily the joints of the spine and the gut respectively. Genes play a major role in determining the risk of each disease, and it is likely that those genes cause the disease by interaction with some environmental factor, most likely bacteria residing in the gut. This study aims to test that hypothesis by profiling the bacteria in the gut of patients with the diseases and healthy subjects.
The Role Of Host Proteases In Modulating Enteric Infectious Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,267,155.00
Summary
Bacterial pathogens that cause gut diseases result in 2.5 million deaths per year. The gut is a complex environment consisting of numerous factors that must be balanced to maintain enteric health. When these factors are unbalanced, disease can occur, and infections can cause imbalances. This project will increase our understanding of the role that host proteins play in gut infections, providing knowledge critical for developing improved strategies for disease treatment and prevention.
Eradication Of High-risk Bacterial Clones Using Bacteriophages
Funder
National Health and Medical Research Council
Funding Amount
$685,070.00
Summary
Nature offers remedies to the spread of dangerous antibiotic resistant bacteria in the form of predatory viruses (bacteriophages). In this project, we will define optimal mixtures of these for killing problem bacterial types, the mechanisms by which bacterial resistance develops, the best approach to identifying susceptible bacteria and to using these viruses to eradicate them, and we will test a carefully optimised bacteriophage therapy in humans colonised by the dangerous E. coli ST131 strain.
Environmental Regulation Of Virulence In Attaching And Effacing Enterobacteria
Funder
National Health and Medical Research Council
Funding Amount
$569,063.00
Summary
Disease-causing bacteria must respond to the extreme conditions, such as acid and bile, which they encounter in their hosts. They achieve this by sensing their environment and activating genes that enhance their survival and ability to cause disease. In this project we will define the mechanisms by which these sensing and response pathways occur, using E. coli as a model. The information obtained from this research should lead to new strategies to treat and prevent bacterial infections.