Pathogenesis Of Infections With Yersinia Enterocolitica
Funder
National Health and Medical Research Council
Funding Amount
$339,634.00
Summary
Yersinia enterocolitica is a significant cause of food-poisoning, gastroenteritis and abdominal pain which may be mistaken for acute appendicitis. Y. enterocolitica is a heterogenous bacterial species only some strains of which are able to cause disease. Many of the disease-causing strains have readily identifiable virulence determinants which facilitate their detection in clinical microbiological laboratories. By contrast, other types, in particular the biotype 1A strains, lack these determinan ....Yersinia enterocolitica is a significant cause of food-poisoning, gastroenteritis and abdominal pain which may be mistaken for acute appendicitis. Y. enterocolitica is a heterogenous bacterial species only some strains of which are able to cause disease. Many of the disease-causing strains have readily identifiable virulence determinants which facilitate their detection in clinical microbiological laboratories. By contrast, other types, in particular the biotype 1A strains, lack these determinants, although many of them are significantly associated with disease. During the past few years, we have compared biotype 1A strains of Y. enterocolitica obtained from patients with those from non-clinical sources in a number of assays for virulence-associated properties. These studies have shown that clinical isolates differ from non-clinical ones in terms of their ability to (1) invade epithelial cells in vitro and intestinal absorptive cells in vivo, (2) escape from epithelial cells and macrophages they have invaded, (3) resist killing by macrophages, and (4) colonise the intestinal tracts of mice. The aim of the study is to identify the bacterial determinants responsible for these differences between clinical and non-clinical strains of Y. enterocolitica biotype 1A. This will be achieved by using genetic techniques to modify virulent strains of biotype 1A at random and then identify derivatives of these bacteria with altered virulence properties. We shall also use genetic techniques to identify genes that are specifically activated when the bacteria come into contact with animal cells and tissues. The results of this research will provide new insights into the virulence mechanisms of Y. enterocolitica and related bacteria, and will be used to develop diagnostic tests which will allow pathogenic strains to be distinguished from harmless ones.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
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
The Roles Of Lipoprotein Multigene Families In Pathogenesis Of Mycoplasma Pneumoniae
Funder
National Health and Medical Research Council
Funding Amount
$257,036.00
Summary
Mycoplasma pneumoniae is one of the most common causes of community acquired pneumonia. Although it can usually be successfully treated with antibiotics, it can result in more severe diseases and can be difficult to diagnose accurately. It has been identified as a target for vaccine development, but this has been hampered by the limited understanding we have of how it causes disease. The attempts at vaccination that have been made have resulted in vaccines which induced more severe, rather than ....Mycoplasma pneumoniae is one of the most common causes of community acquired pneumonia. Although it can usually be successfully treated with antibiotics, it can result in more severe diseases and can be difficult to diagnose accurately. It has been identified as a target for vaccine development, but this has been hampered by the limited understanding we have of how it causes disease. The attempts at vaccination that have been made have resulted in vaccines which induced more severe, rather than less severe, disease. Investigations of several other related bacteria have shown that they are able to vary their surface proteins and thus may evade the immune system, permitting them to cause more prolonged disease. Better understanding how this occurs, and what this enables the bacteria to do, may assist in developing improved vaccine strategies. This project aims to investigate the six gene families in Mycoplasma pneumoniae which are known to encode surface proteins and establish how and why the bacteria switch from one gene to another during infection. In addition the capacity of bacteria expressing different versions of the six surface proteins to adhere to different tissues will be investigated. Once this is known, these mechanisms may be able to be specifically disrupted to prevent a strain of Mycoplasma pneumoniae from being able to establish prolonged infections. Such a strain might be a useful basis for an effective vaccine.Read moreRead less