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
How A Multidrug Resistant Bacterial Pathogen Has Become Pandemic
Funder
National Health and Medical Research Council
Funding Amount
$1,116,544.00
Summary
The pandemic spread of antibiotic resistant E. coli ST131 is a major human health problem. ST131 is the globally dominant cause of urinary tract and bloodstream infections. This project will use advanced genetics and animal infection models to understand the features of ST131 that have fueled its global dominance. The outcomes will unravel the molecular mechanisms that enable ST131 to persist and cause repeat infection, and guide the development of new precision medicine therapeutics.
E. coli is a normal inhabitant of the human intestine, but some varieties can cause serious infections that may lead to the premature death of children, especially in less developed countries. The aims of this study are to learn more about these harmful varieties of E. coli and to enhance our ability to detect them in samples from patients and the environment.
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.
Role Of Macrophages In Uropathogenic E. Coli Infections
Funder
National Health and Medical Research Council
Funding Amount
$574,890.00
Summary
Urinary tract infections (UTI) are one of the most common types of infections in humans. They are also a major cause of septic shock, a condition with high fatality rates. Uropathogenic Escherichia coli (UPEC) are the major microbes causing UTI in humans. This project addresses the role of an immune cell type, the macrophage, in UPEC-mediated disease. The outcomes of this project will be a better understanding of how UPEC causes disease, and potentially new treatment regimes for UTI.