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Molecular Analysis Of Regulation Of Virulence Gene Expression In Pathogenic E. Coli Strains (ETEC And Atypical EPEC)
Funder
National Health and Medical Research Council
Funding Amount
$289,258.00
Summary
Infectious diarrhoea is one of the commonest human afflictions worldwide, and is responsible for the deaths of millions of children each year. One of the principal causes of diarrhoea is pathogenic E. coli, which are classified into several groups according to the factors they employ to cause disease. One type of pathogenic E. coli, known as enterotoxigenic E. coli (ETEC), causes diarrhoea resembling cholera in children in less developed countries and in adult travellers to those countries. Anot ....Infectious diarrhoea is one of the commonest human afflictions worldwide, and is responsible for the deaths of millions of children each year. One of the principal causes of diarrhoea is pathogenic E. coli, which are classified into several groups according to the factors they employ to cause disease. One type of pathogenic E. coli, known as enterotoxigenic E. coli (ETEC), causes diarrhoea resembling cholera in children in less developed countries and in adult travellers to those countries. Another type is enteropathogenic E. coli (EPEC), which causes acute and persistent diarrhoea in children worldwide. Recent studies in Melbourne and Darwin have shown that EPEC are a particularly common cause of diarrhoea in children living in those cities. Individual groups of E. coli use different strategies to cause infection. In the case of ETEC, the key step in infection is the injection of bacterial toxins into intestinal cells. These toxins perturb the ability of these cells to transport water and electrolytes across their membrane. In contrast, infection with EPEC is characterised by intimate adherence of the bacteria to the lining of the intestine, causing structural damage to intestinal cells. Because the synthesis of virulence factors is an energy-costly process for bacteria, pathogenic varieties of E. coli have evolved sophisticated mechanisms to control the production of these factors, so that they are made only when needed, e.g., under environmental conditions like those in the gut. In this project, we will investigate the ways by which ETEC and EPEC sense and respond to environmental signals to produce their virulence determinants. The identification of specific control genes and proteins of these bacteria may lead to the development of novel diagnostic tools for EPEC and help us to devise new treatment strategies to block the production of virulence factors by pathogenic E. coli.Read moreRead less
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.
Class-specific Virulence Determinants Of Atypical Enteropathogeneic E. Coli
Funder
National Health and Medical Research Council
Funding Amount
$672,134.00
Summary
Some varieties of E. coli cause diarrhoea, but they are difficult to diagnose in the laboratory. The aim of this study is to find specific genes of disease-associated E. coli that could be used as targets to identify these bacteria in patients with diarrhoea. The discovery of genes from E. coli that could be used as diagnostic targets will provide invaluable tools to study the epidemiology and clinical impact of these bacteria in patients in Australia and overseas.
Novel Antimicrobials That Target Enteropathogenic Escherichia Coli
Funder
National Health and Medical Research Council
Funding Amount
$617,525.00
Summary
Enteropathogenic E. coli (EPEC) cause acute and persistent diarrhoea which affect the health of millions of children each year. In this study, we will use the state-of-the-art-technology to identify small synthetic-compounds that inhibit the virulence of EPEC without affecting normal microflora. Molecular, cellular and animal tests of the compounds will be carried out to determine whether they can be used to treat gastrointestinal infection by EPEC.
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.
Identification And Characterisation Of Novel Virulence Genes In Attaching And Effacing Strains Of Escherichia Coli
Funder
National Health and Medical Research Council
Funding Amount
$281,320.00
Summary
Some varieties of Escherichia (E.) coli are harmless bacteria that live in the healthy intestinal tract, whereas others can cause diarrhoea. Those varieties of E. coli which cause diarrhoea include so-called enteropathogenic E. coli (EPEC), which is a leading cause of life- diarrhoea in infants and young children in less developed countries, and enterohaemorrhagic E. coli (EHEC) the cause of hamburger disease. These bacteria are able to cause disease because they possess specific genetic informa ....Some varieties of Escherichia (E.) coli are harmless bacteria that live in the healthy intestinal tract, whereas others can cause diarrhoea. Those varieties of E. coli which cause diarrhoea include so-called enteropathogenic E. coli (EPEC), which is a leading cause of life- diarrhoea in infants and young children in less developed countries, and enterohaemorrhagic E. coli (EHEC) the cause of hamburger disease. These bacteria are able to cause disease because they possess specific genetic information that is absent from harmless varieties of E. coli. Although many of these disease-associated genes have been identified, the specific role of many of them is not known. In addition, it seems likely that many more genes of this type remain to be discovered. The fact that EPEC is host specific means that the mechanisms by which these bacteria cause disease can only be investigated in humans. This is extremely limiting for the number and type of investigations that can be performed. However, there are rabbit-specific strains of EPEC which cause a disease in rabbits that is indistinguishable from that caused by EPEC in children. The aims of this study are to use the rabbit model of diarrhoea to learn more about the contribution of certain specific factors of EPEC to disease causation and to discover new factors of this type. This will be achieved by three complementary strategies: (1) investigating rabbit E. coli for virulence genes and determining if they are present in human strains; (2) examining the effect of inactivating these genes on the ability of E. coli to cause diarrhoea in rabbits; and (3) infecting rabbits with pools of mutant E. coli strains to identify factors that the bacteria require to survive in rabbits. The results of these studies will improve understanding of the mechanisms by which E. coli cause disease and may provide opportunities for the development of novel tools to diagnose, treat and prevent E. coli-associated diarrhoea.Read moreRead less