Characterisation Of A Novel Type Of Promoter Controlling Expression Of Virulence Genes In Neisseria.
Funder
National Health and Medical Research Council
Funding Amount
$200,880.00
Summary
This project will investigate how two different types of bacteria control genes that are involved in determining their disease-causing ability. The expression of many bacterial genes is controlled by a sophisticated battery of regulatory systems that respond to individual, very specific, environmental signals. Such regulatory systems are capable of exerting very precise control over the level of gene expression, in response to the concentration of specific molecules in the immediate environment. ....This project will investigate how two different types of bacteria control genes that are involved in determining their disease-causing ability. The expression of many bacterial genes is controlled by a sophisticated battery of regulatory systems that respond to individual, very specific, environmental signals. Such regulatory systems are capable of exerting very precise control over the level of gene expression, in response to the concentration of specific molecules in the immediate environment. However, there is evidence to suggest that many important disease-causing bacteria are much less reliant on specific regulatory systems. Instead, these bacteria rely more heavily what have been termed global systems for the regulation of gene expression. Such systems typically respond to less specific signals, such as the growth rate of the bacterial cell, but nevertheless appear capable of very precise control. We have evidence for a previously uncharacterised type of global control system that appears to be widespread amongst bacteria. It is likely that many virulence genes in a variety of disease-causing bacteria will prove to be controlled by similar means. Therefore this project will not only provide an insight into how expression of these particular virulence determinants is regulated, but will yield data that may help in our understanding of precise global regulatory processes in other bacterial species of medical importance.Read moreRead less
Pathogenomics: New Ways To Exploit Genome Sequence Data From Pathogenic Bacteria.
Funder
National Health and Medical Research Council
Funding Amount
$547,372.00
Summary
Bacterial pathogens are locked in an evolutionary battle of survival with their eukaryote hosts. The rapidly evolving genes of medically-important pathogens are generally those required for adaptation to the human host. This project aims to exploit the abundance of available bacterial genome sequences to predict rapid evolution in bacterial pathogens using computational methods. The protein products of such genes offer novel targets for therapeutic intervention.
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.
Characterisation Of Enterohaemorrhagic Escherichia Coli Lacking Classical Virulence Markers
Funder
National Health and Medical Research Council
Funding Amount
$140,660.00
Summary
Some intestinal infections with the intestinal bacterium, E. coli, can result in severe, often fatal, kidney disease called the haemolytic uraemic syndrome. It is important for the diagnosis and treatment of this condition that the infections are detected swiftly. Current means of identifying this virulent form of E. coli are inadequate and do not account for all types of the bacteria that can cause severe disease. Children are particularly susceptible to life threatening infections with this ty ....Some intestinal infections with the intestinal bacterium, E. coli, can result in severe, often fatal, kidney disease called the haemolytic uraemic syndrome. It is important for the diagnosis and treatment of this condition that the infections are detected swiftly. Current means of identifying this virulent form of E. coli are inadequate and do not account for all types of the bacteria that can cause severe disease. Children are particularly susceptible to life threatening infections with this type of E.coli and usually acquire the infection by consuming contaminated food or water. This organism is currently a global food safety problem and the bacteria are especially prevalent in ground beef products and water or vegetables that have been contaminated with cattle faeces. In this study we aim to identify new bacterial genes and proteins that may be used to improve current means of detecting and diagnosing this kind of E.coli. A great deal is known about the way in which the classical strains of this virulent E .coli colonise the intestine however a small but significant group of these organisms do not carry known colonisation factors. We aim to identify bacterial proteins in these non-classical strains of E.coli which are needed for attachment of the bacteria to the host. Identifying how these bacteria interact with the host may help us to develop improved means of detecting and diagnosing this life-threatening infection.Read moreRead less
Identification And Analysis Of Novel Replication Initiation Factors In Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$311,789.00
Summary
Multi-drug resistant Golden staph is a serious medical problem around the world because strains are often resistant to commonly used treatments; new drugs are therefore urgently required. DNA replication is a fundamental process that is essential for the survival of all cellular organisms. This project aims to identify and characterise novel factors involved in DNA replication in Golden staph, which represent potential drug targets.
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
DNA Segregation In Multiresistant Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$306,592.00
Summary
Strains of Golden Staph bacteria resistant to many antibiotics are a major cause of hospital-acquired, and increasingly community-acquired, infections in Australia and around the world. Bacterial growth depends on the faithful inheritance of genetic material, which is facilitated by active DNA segregation. This project will elucidate key aspects of segregation processes so that treatments can be devised that interfere with the growth of this important pathogen and the development of resistance.
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 rapid emergence and spread of antibiotic resistance in bacteria that cause infectious diseases is of major concern to public health authorities throughout the world. Many of the genes that are responsible for this resistance are carried on mobile genetic elements, which are discrete segments of genetic material that can move from one bacterium to another. These genetic elements are important vehicles for the transmission of virulence and antibiotic resistance genes in most bacteria. This pro ....The rapid emergence and spread of antibiotic resistance in bacteria that cause infectious diseases is of major concern to public health authorities throughout the world. Many of the genes that are responsible for this resistance are carried on mobile genetic elements, which are discrete segments of genetic material that can move from one bacterium to another. These genetic elements are important vehicles for the transmission of virulence and antibiotic resistance genes in most bacteria. This project is centred on bacteria that cause intestinal diseases and have the potential to transfer genetic information to other bacteria that are present in the intestine. The focus will be on elucidating the mechanism of action of an enzyme encoded by two of these genetic elements. This enzyme is responsible for the movement of these elements from one site in the bacterial genome to another, by a process that is being increasingly recognised as important in antibiotic-resistant disease-causing bacteria. The project will employ the latest tools of molecular biology to determine the function of this enzyme, and its associated genetic elements, at the detailed molecular level. These studies will contribute to our understanding of how these antibiotic resistance elements are transferred within and between different bacterial cells. In the longer term the project will contribute towards the development of improved methods for the control and treatment of infectious diseases.Read moreRead less