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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
A New Genomic Frontier For Foodborne Disease Investigation In Australia
Funder
National Health and Medical Research Council
Funding Amount
$750,520.00
Summary
Foodborne diseases caused by bacteria such as Salmonella and Campylobacter are a huge public health problem, both in Australia and globally. Current methods used to investigate foodborne disease may not be sensitive enough to track foodborne outbreaks, and may not even detect them in the first place. We propose using cutting-edge molecular techniques to investigate foodborne outbreaks, and we think that using these methods will enable outbreaks to be interrupted at a much earlier stage.
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.
Characterisation Of A Newly-discovered, Virulence-associated, Protein Secretion System Of Enteropathogenic E. Coli
Funder
National Health and Medical Research Council
Funding Amount
$582,149.00
Summary
The cell walls of bacteria act as a barrier to the export of any proteins they produce. We recently discovered a protein secretion system, which diarrhoea-causing strains of E. coli require to cause disease. The aim of this study is to characterise this secretory system, and discover how it functions and what it secretes. The knowledge obtained from this research will shed new light on how E. coli causes disease and could reveal novel methods to treat and prevent infections with this bacterium.
The Role Of Voltage-gated Na+ And Ca2+ Channels In Post-inflammatory Hyperexcitability Of Enteric Neurons
Funder
National Health and Medical Research Council
Funding Amount
$520,000.00
Summary
Gastrointestinal inflammation causes changes in neurons that control gut functions (motility and secretion). These changes in neuronal properties lead to the development of post-inflammatory motility disorders. This will be the first detailed study of neuronal ion channels that are changed after inflammation in the gut. Our study will open the way to the development of therapeutic agents to treat post-inflammatory IBS and other conditions that involve disorders of motility.
Understanding And Preventing Gastroenteritis And Foodborne Disease In Elderly Australians
Funder
National Health and Medical Research Council
Funding Amount
$69,684.00
Summary
Foodborne and gastrointestinal diseases amongst older people are an emerging concern for the Australian public and an overstretched health care system. In this study, I will undertake research to understand the pattern of disease among elderly people using data from national surveys of gastroenteritis and surveillance of infectious diseases. This study will provide evidence for strategies to control foodborne disease and gastroenteritis in elderly people and aged care homes.
Identifying Pragmatic Strategies To Prevent And Treat Enteric Infection In Indigenous Infants
Funder
National Health and Medical Research Council
Funding Amount
$189,384.00
Summary
Diarrhoea remains one of the commonest causes of death in young children. Most of these deaths occur in places that have limited clean water, food, and health care. Although deaths from diarrhoea are rare in Australia, Indigenous children still suffer from frequent and severe episodes of diarrhoea, much more so that than non-Indigenous infants. This research aims to reduce this suffering by finding ways to both prevent and treat diarrhoea in young children.
Examination Of The Role Of Biofilms In Infection With Enteropathogenic Escherichia Coli
Funder
National Health and Medical Research Council
Funding Amount
$456,382.00
Summary
Many infections are caused by bacteria living in communities, known as biofilms. Enteropathogenic E. coli (EPEC) is a major cause of diarrhoea and results in the death of millions of children annually. We have found a link between biofilm formation by EPEC and disease. In this project we will examine how biofilm formation by EPEC occurs and the contribution of biofilm formation to disease. The results of this study may indicate new ways to treat and prevent E. coli diarrhoea.
Understanding The Role Of Infectious Agents As A Trigger Of Crohns Disease In Children With Early Onset Disease
Funder
National Health and Medical Research Council
Funding Amount
$570,876.00
Summary
Crohn's disease is a major cause of illness throughout the world. There is no cure and current therapies carry substantial risks. An infectious agent has been suggested as the trigger for disease but research has been inconclusive. Our study focuses on the characterisation of a novel virus we have identified that may trigger Crohn's disease in children at disease onset.