A comprehensive analysis of the outer membrane, surface exposed and secreted proteome of Pasteurella multocida. Pasteurella multocida is the causative agent of a range of animal diseases. The molecular mechanisms of P. multocida pathogenesis are poorly understood and the current vaccines generally ineffective. We will identify all P. multocida outer membrane, surface exposed and secreted proteins expressed during natural infection, or under conditions which mimic natural infection, by a global p ....A comprehensive analysis of the outer membrane, surface exposed and secreted proteome of Pasteurella multocida. Pasteurella multocida is the causative agent of a range of animal diseases. The molecular mechanisms of P. multocida pathogenesis are poorly understood and the current vaccines generally ineffective. We will identify all P. multocida outer membrane, surface exposed and secreted proteins expressed during natural infection, or under conditions which mimic natural infection, by a global proteomics approach. We believe that secreted proteins and those found on the outer surface of the bacterial cell are likely to be crucial virulence determinants. The expected outcomes are the identification of a number of candidate vaccine antigens and an enhanced understanding of Pasteurella pathogenesis.Read moreRead less
Recombinant probiotics for prevention of enteric infections in piglets. Shigatoxigenic and enterotoxigenic strains of Escherichia coli cause severe diarrhoeal disease and oedema disease in piglets. The resultant morbidity and mortality is a major cause of financial loss to the pig industry both in Australia and overseas. We have conceived a highly novel approach to prevention of these diseases involving molecular mimicry of host receptors for the E. coli toxins and adhesins on the surface of a ....Recombinant probiotics for prevention of enteric infections in piglets. Shigatoxigenic and enterotoxigenic strains of Escherichia coli cause severe diarrhoeal disease and oedema disease in piglets. The resultant morbidity and mortality is a major cause of financial loss to the pig industry both in Australia and overseas. We have conceived a highly novel approach to prevention of these diseases involving molecular mimicry of host receptors for the E. coli toxins and adhesins on the surface of a harmless bacterium. Oral administration of this agent to piglets has the potential to bind free toxins in the gut and prevent colonization of the intestines by the pathogens, thereby preventing disease.Read moreRead less
Vaccine against leptospirosis. This project will utilise the information from the determination of the complete genome sequence of Leptospira borgpetersenii serovar Hardjobovis at Monash University. Bioinformatics analysis will be used to allow a global approach to identify all putative vaccine antigens which will be cloned, expressed and purified and their protective capacity investigated.
Functional genomics of large clostridial plasmids. The aims of this genomics project are to determine how large DNA elements called plasmids are able to be transferred between different strains of a bacterium that causes disease in domestic livestock. These plasmids carry genes that encode the potent protein toxins that are responsible for several diseases. To understand how these diseases are spread we must learn how the plasmids have evolved and whether they can move from bacterium to bacteriu ....Functional genomics of large clostridial plasmids. The aims of this genomics project are to determine how large DNA elements called plasmids are able to be transferred between different strains of a bacterium that causes disease in domestic livestock. These plasmids carry genes that encode the potent protein toxins that are responsible for several diseases. To understand how these diseases are spread we must learn how the plasmids have evolved and whether they can move from bacterium to bacterium. The successful completion of the project will result in a detailed understanding of genetic elements that are important mediators of several diseases of importance to Australian primary industry.Read moreRead less
Characterising post-translational modifications in bacterial proteins. This project represents the first global attempt to characterize post-translational modifications in bacterial proteins using the tools of proteomics. Modifications to proteins are key elements in altering their function. In bacteria, modifications are important in cell-cell adhesion, signalling and triggering of the immune response. Characterisation of modified proteins and their sites of modification represents an opportuni ....Characterising post-translational modifications in bacterial proteins. This project represents the first global attempt to characterize post-translational modifications in bacterial proteins using the tools of proteomics. Modifications to proteins are key elements in altering their function. In bacteria, modifications are important in cell-cell adhesion, signalling and triggering of the immune response. Characterisation of modified proteins and their sites of modification represents an opportunity to understand how bacterial cell populations communicate in the environment, as well as aid in understanding pathogenesis in medical, veterinary and food-borne pathogens. Therefore, improved vaccine targets and therapeutics, as well as method-based products, may be generated by this project.Read moreRead less
Pathogenesis, regulation and genomics of the ovine footrot pathogen, Dichelobacter nodosus. Footrot is one of the most economically significant diseases of sheep in Australia. The aim of this project is to develop a detailed understanding of how the bacterium that causes this infection is able to infect the sheep hoof and result in clinical disease. The complete sequence of the genome of the causative bacterium will be determined, enabling us to deduce its genetic potential. The completed projec ....Pathogenesis, regulation and genomics of the ovine footrot pathogen, Dichelobacter nodosus. Footrot is one of the most economically significant diseases of sheep in Australia. The aim of this project is to develop a detailed understanding of how the bacterium that causes this infection is able to infect the sheep hoof and result in clinical disease. The complete sequence of the genome of the causative bacterium will be determined, enabling us to deduce its genetic potential. The completed project will significantly advance fundamental knowledge of the disease process and will lead to the development of improved methods for the control of the disease, with concomitant cost savings to Australian primary industry.Read moreRead less
Proteomics and vaccine development in swine dysentery. Swine dysentery is an infectious disease of significant economic importance caused by Brachyspira hyodysenteriae. There is no effective vaccine available. This project will combine modern techniques in microbial genomics and proteomics to identify outer membrane proteins of B. hyodysenteriae and evaluate their role as candidate vaccine antigens.
Dissociation of a Tetrameric Enzyme with Interface-Targeted Peptides. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics and an equally urgent need to characterise new antibiotic targets. One such target is dihydrodipicolinate synthase (DHDPS) which catalyses the critical step in lysine and cell wall biosynthesis in bacteria. This proposal aims to generate new drugs targeting DHDPS for effective and rapid treatment of bacterial infections, including gastro ....Dissociation of a Tetrameric Enzyme with Interface-Targeted Peptides. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics and an equally urgent need to characterise new antibiotic targets. One such target is dihydrodipicolinate synthase (DHDPS) which catalyses the critical step in lysine and cell wall biosynthesis in bacteria. This proposal aims to generate new drugs targeting DHDPS for effective and rapid treatment of bacterial infections, including gastroenteritis. Recent statistics show that over 5 million Australians suffer from gastroenteritis each year and hospitalisation for this infection is nearly seven times higher for indigenous than non-indigenous children. Accordingly, this research has the potential to assure a healthier future for millions of Australians.Read moreRead less
Inhibitors of meso-diaminopimelic acid (meso-DAP) and lysine biosynthesis: targeting dihydrodipicolinate synthase. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics with novel modes of action. This project aims to generate new drug candidates that target dihydrodipicolinate synthase (DHDPS) - the first enzyme in the synthesis of the bacterial cell wall - using a triple-pronged approach. This novel approach will allow for the development of new drugs to tr ....Inhibitors of meso-diaminopimelic acid (meso-DAP) and lysine biosynthesis: targeting dihydrodipicolinate synthase. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics with novel modes of action. This project aims to generate new drug candidates that target dihydrodipicolinate synthase (DHDPS) - the first enzyme in the synthesis of the bacterial cell wall - using a triple-pronged approach. This novel approach will allow for the development of new drugs to treat a range of pathogenic bacteria, including "Golden Staph".Read moreRead less
Phase-variable epigenetic regulators in bacterial veterinary pathogens. This project aims to identify phasevarion regulated genes in the major bacterial swine pathogens Streptococcus suis and Actinobacillus pleuropneumoniae. Both species contain randomly switching epigenetic regulators that control expression of multiple genes by epigenetic mechanisms. Identifying phasevarion controlled genes will inform and direct future vaccine development for important livestock species.