Contribution Of Shigella And Escherichia Coli Pathogenicity Islands To Diarrhoeal Disease
Funder
National Health and Medical Research Council
Funding Amount
$303,677.00
Summary
Diarrhoea resulting from infection with Shigella and Escherichia coli is a major cause of sickness and death in the developing world, especially in children. Even in Australia, these bacteria, which may be food borne, are occasionally responsible for life threatening infections. In this study, we will investigate the contribution to diarrhoeal disease of large fragments of foreign DNA which have been recently acquired by these bacteria. We will characterise several of these elements in detail, i ....Diarrhoea resulting from infection with Shigella and Escherichia coli is a major cause of sickness and death in the developing world, especially in children. Even in Australia, these bacteria, which may be food borne, are occasionally responsible for life threatening infections. In this study, we will investigate the contribution to diarrhoeal disease of large fragments of foreign DNA which have been recently acquired by these bacteria. We will characterise several of these elements in detail, identifying novel virulence determinants and toxins in the process. We will also explore the means by which these packages of nasty DNA transfer between bacteria and investigate their potential to give rise to new, more virulent strains of bacteria. This study is particularly significant because it will lead to an improved understanding of how bacteria cause disease and may help to guide us in developing better strategies for the prevention of bacterial diarrhoea. Specifically, the work done on characterising large clusters of virulence genes will allow us to construct safer bacterial vaccines and we expect that in the future this knowledge will contribute to the development of new and better diagnostic and therapeutic agents against these harmful bacteria.Read moreRead less
Analysis And Regulation Of Leptospiral Virulence Factors.
Funder
National Health and Medical Research Council
Funding Amount
$630,465.00
Summary
Leptospirosis is a globally important infectious disease caused by Leptospira spp. This project aims to identify and characterise factors which play a role in disease development by knocking out genes, then investigating the impact on overall gene-protein expression in the mutant strain and its ability to cause disease. This will allow us to gain insights on mechanisms by which Leptospira spp. cause disease, leading to development of better methods of disease control and prevention.
Dissemination And Virulence Properties Of The She Pathogenicity Island Of Shigella Flexneri.
Funder
National Health and Medical Research Council
Funding Amount
$110,625.00
Summary
Bacterial species belonging to the genus Shigella are responsible for intestinal diseases ranging from mild diarrhoea to life threatening bacillary dysentery. Such diseases kill over a million people, mainly infants in developing countries, every year and lead to serious morbidity and mortality even in industrialised countries with well developed health care systems. In many cases the virulence of Shigella species is augmented by large fragments of DNA, called pathogenicity islands, that carry g ....Bacterial species belonging to the genus Shigella are responsible for intestinal diseases ranging from mild diarrhoea to life threatening bacillary dysentery. Such diseases kill over a million people, mainly infants in developing countries, every year and lead to serious morbidity and mortality even in industrialised countries with well developed health care systems. In many cases the virulence of Shigella species is augmented by large fragments of DNA, called pathogenicity islands, that carry genes which contribute to the development of disease (pathogenesis) in humans. Pathogenicity islands are important genetic elements which appear to spread independantly throughout bacterial populations and therefore contribute to the emergence of new virulence traits in bacteria. Recently, we identified two related pathogenicity islands carried by both Shigella flexneri and other species of the genus Shigella. The two pathogenicity islands belong to a unique class of genetic elements found in Shigella species and virulent strains of the intestinal bacterium E. coli. Our current study is aimed at (1) understanding the mechanisms by which one of these islands, the she pathogenicity island, spreads from one bacterial strain to another to introduce disease-producing or virulence genes to new bacteria and (2) to study how the sigA virulence gene, carried on the she pathogenicity island, contributes to disease development in humans. We know that sigA encodes a protein toxin which contributes to the loss of fluid from the intestines of rabbits that have been experimentally infected with Shigella flexneri. We propose to study the structure and function of the SigA protein to determine how it interacts with tissues to produce a pathological state. Such studies will enhance our understanding of the process of disease development and contribute to the investigation and assessment of new strategies for therapeutic intervention.Read moreRead less
Outer Membrane Proteins Of Leptospira; Role In Immunity And Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$88,500.00
Summary
Leptospirosis is a significant cause of death in tropical regions of the world. Recent outbreaks in Nicaragua and Brazil are timely reminders of the seriousness of disease caused by the Leptospira bacteria. In these outbreaks >10% of people developing the disease did not recover. Spread of the disease does not occur from person to person, but rather from animal to human. Leptospira are shed from infected animals via the urine; human infection may occur through contact with infected urine or u ....Leptospirosis is a significant cause of death in tropical regions of the world. Recent outbreaks in Nicaragua and Brazil are timely reminders of the seriousness of disease caused by the Leptospira bacteria. In these outbreaks >10% of people developing the disease did not recover. Spread of the disease does not occur from person to person, but rather from animal to human. Leptospira are shed from infected animals via the urine; human infection may occur through contact with infected urine or urine contaminated materials. In Australia, leptospirosis is an occupational hazard with dairy farmers, pig handlers, banana pickers and abattoir workers being those most at risk. A recent and alarming development is the emergence of new risk groups associated with certain leisure activities. For example, in the USA three triathletes died from leptospirosis and it was subsequently determined that the source of infection was contaminated swimming water. This project will investigate aspects of the development of disease and immunity during infection by Leptospira. This will be achieved by analysing the set of proteins located on the surface of the bacterium. These proteins play a key role in the development of disease. Using state of the art technology, each of the proteins will be purified and identified. This will enable experiments that will enhance our understanding of the development of disease at a molecular level.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.
Virulence Mechanisms In Hypervirulent Epidemic Strains Of Clostridium Difficile.
Funder
National Health and Medical Research Council
Funding Amount
$499,135.00
Summary
The bacterium Clostridium difficile is the major cause of nosocomial diarrhoea in many countries, including Australia. More virulent isolates have emerged since 2000, leading to increased incidence and severity of disease in many countries and resulting in epidemics. This project will make a major contribution to our understanding of how these bacteria cause disease and may help to prevent outbreaks of the hypervirulent strains in Australia by identifying potential new vaccine candidates.
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
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
Coordinate Expression Of Virulence Factors In Pathogenic Escherichia Coli
Funder
National Health and Medical Research Council
Funding Amount
$239,250.00
Summary
Escherichia coli is a versatile pathogen capable of causing a range of disease types including diarrhoea, dysentery, haemolytic uremic syndrome, bladder and kidney infections, septicaemia, pneumoniae and meningitis. Infections due to pathogenic E. coli may be limited to mucosal surfaces or can disseminate throughout the body. Amongst the different classes of pathogenic E. coli, diarrheagenic strains (namely enterotoxigenic and enteroinvasive E. coli) are responsible for the death of an estimated ....Escherichia coli is a versatile pathogen capable of causing a range of disease types including diarrhoea, dysentery, haemolytic uremic syndrome, bladder and kidney infections, septicaemia, pneumoniae and meningitis. Infections due to pathogenic E. coli may be limited to mucosal surfaces or can disseminate throughout the body. Amongst the different classes of pathogenic E. coli, diarrheagenic strains (namely enterotoxigenic and enteroinvasive E. coli) are responsible for the death of an estimated one million humans per year, mainly in third world countries. The majority (80%) of urinary tract infections (UTIs) in humans are caused by E. coli and in Australia alone there are about 250,000 cases per year. It is estimated that one in four women and one in twenty men will develop a urinary tract infection in their lifetime. Pathogenic E. coli strains are normally equipped with multiple virulence factors and there is mounting evidence that the expression of such factors is finely orchestrated by mutual regulatory cross-talk. For example, expression of flagella (which provide motility) and adhesins (which provide attachment) are fundamentally counteracting phenotypes, yet the molecular and genetic mechanisms that coordinate their expression are unknown. I plan to examine inter-system cross-regulation of bacterial surface structures (namely adhesins, autoaggregaters, capsules and flagella). The aim is to understand on the molecular level how microorganisms orchestrate expression of virulence factors and will have consequences for our understanding of microbial pathogenicity. The strategy outlined may lead to new routes for strain attenuation and perhaps a method for vaccine strain construction. The research will be performed in collaboration with international high profile partners.Read moreRead less