Molecular Typing Of Salmonella Enterica Serovar Typhimurium
Funder
National Health and Medical Research Council
Funding Amount
$272,545.00
Summary
Salmonella mainly causes food poisoning and is a significant human health problem. Different Samonella forms are identified by serotyping and many serovars have been given a name . There are more than 2000 serovars. The best known serovar is Typhimurium which is the cause of 40% of salmonella infections. Typhimurium is so frequently involved in infections it is necessary to further divide it for outbreak investigations and long term monitoring of the organism. The only widely used method to subd ....Salmonella mainly causes food poisoning and is a significant human health problem. Different Samonella forms are identified by serotyping and many serovars have been given a name . There are more than 2000 serovars. The best known serovar is Typhimurium which is the cause of 40% of salmonella infections. Typhimurium is so frequently involved in infections it is necessary to further divide it for outbreak investigations and long term monitoring of the organism. The only widely used method to subdivide Typhimurium is phage typing, which is done only in major laboratories (2 in Australia). Phage typing is based on lysis patterns of a test isolate to a set of 34 phages. Phage typing has played a crucial role in tracking the organism, for example the emergence of a multidrug resistance new type (DT204c) in UK and US. The technique is simple but the problem is that reactions vary with slight change in conditions and scoring the reaction results is very subjective. We propose to replace the typing system with one based on the DNA method PCR, so it will be simple, fast and accurate. We will use a DNA fingerprinting technique called AFLP (amplified fragment length polymorphism) to find markers (DNA segments) that are specific to phage types and design PCR assays based on the markers we find. Such a typing system will retain the essence of phage typing by providing continuity of the valuable epidemiological database on phage types. Further the typing system could easily be expanded to accommodate any new types by finding more markers while the current phage typing system is very difficult to expand (last done in 1977 and is behind in our needs). This project will establish a general approach for designing typing systems based on molecular biology for other pathogens and could have a major impact on the surveillance of bacterial infections in the 21st century.Read moreRead less
Intracellular Survival Of Burkholderia Pseudomallei And Evasion Of Autophagy
Funder
National Health and Medical Research Council
Funding Amount
$450,799.00
Summary
Melioidosis is a disease with high mortality that is caused by the bacterium Burkholderia pseudomallei. Autophagy is a natural part of the mammalian immune system. This project seeks to explain how Burkholderia pseudomallei avoids killing by host autophagy and identify the bacterial factors necessary for its survival within cells. The identified genes will be future targets for medical intervention.
Glycosylation Of Pili In Pathogenic Neisseria: Function In Disease And Potential As A Vaccine Antigen
Funder
National Health and Medical Research Council
Funding Amount
$150,880.00
Summary
Disease caused by Group B Neisseria meningitidis and Neisseria gonorrhoeae remain a significant health problem worldwide. There are currently no vaccines available for either of these bacteria. A surface structure found on these bacteria, called pili, are key in host colonisation and disease. Genetics and structural studies have identified that the protein subunits, which make up pili, are glycosylated - modified by the addition of sugars. The role of glycosylation in the disease process is not ....Disease caused by Group B Neisseria meningitidis and Neisseria gonorrhoeae remain a significant health problem worldwide. There are currently no vaccines available for either of these bacteria. A surface structure found on these bacteria, called pili, are key in host colonisation and disease. Genetics and structural studies have identified that the protein subunits, which make up pili, are glycosylated - modified by the addition of sugars. The role of glycosylation in the disease process is not known. It is possible that the glycosylation of pili is required for attachment to host cells or perhaps in evasion of the immune system. In our current studies, we have identified and analysed a number of genes involved in pili glycosylation, in bacteria which make structre that are know. We have also identified a series of new genes we believe are also involved in glycosylation. Some of these genes are involved in the biosynthesis of unknown structures and are common in bacteria isolated from patients with meningitis. We will identify these stuctures and characterise bacteria in which these genes have been inactivated so that we can examine the role of pili glycosylation in colonisation and disease. This study has the potential to yield important new information about the process of colonisation and disease, and also has the potential to facilitate novel approaches in vaccine development.Read moreRead less