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
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
Fungi are increasingly causing life-threatening infections. Little is known about the mechanisms underlying these infections. We will compare the genomes of high and low virulent fungal strains to gain insides into the basis of these differences by using C. gattii as model of a globally highly pathogenic fungus. The findings will be generalized by comparing the obtained results with the genomes of other important pathogenic fungi to develop a scientific basis for better treatment strategies.
Novel Antibiotics That Harness Innate Immunity To Overcome Multi-drug Resistant S. Aureus
Funder
National Health and Medical Research Council
Funding Amount
$872,355.00
Summary
Controlling infection with antibiotics is essential in medicine. However, bacterial resistance to antibiotics is growing rapidly. Here, we propose new strategies to treat multi-drug resistant Staphylococcus aureus by combining existing clinical antibiotics with either a targetted immune response or by removing the ability of bacteria to hide from our immune system. These novel approaches will allow us to overcome infections caused by resistant bacteria, which are a serious and growing problem.
Characterisation Of Porphyromonas Gingivalis And Treponema Denticola Interactions In The Development Of A Pathogenic Biofilm
Funder
National Health and Medical Research Council
Funding Amount
$566,200.00
Summary
Gum disease (periodontitis) is an inflammatory disease caused by bacterial pathogens that is the major cause of tooth loss in adults. It is also associated with systemic diseases such as cardiovascular disease. In this study we will determine the mechanisms by which two bacterial species work together to produce the pathogenic dental plaque that causes disease.
Helicobacter Pylori Acquisition Of Host Cholesterol: Its Role In Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$417,380.00
Summary
The bacterium Helicobacter pylori is present in the stomach of half the world’s population. It is estimated that 20% of these people will suffer from peptic ulcer disease, whereas as many as 1% will develop stomach cancer later in life. The common factor in all these diseases is the inflammation induced by the bacterium. This project will investigate a new mechanism by which H. pylori causes inflammation and how dietary cholesterol may be involved in this process.