Safety in numbers: Bacterial aggregation and adaptation to oxidative stress. This project is a new collaboration which links two molecular microbiologists with the complementary skills required to make new insights into the molecular processes that underpin bacterial aggregation and biofilm formation. Biofilms are of immense significance in medical, industrial and environmental settings and so the fundamental information gained from this project will have wider relevance to the field of microbio ....Safety in numbers: Bacterial aggregation and adaptation to oxidative stress. This project is a new collaboration which links two molecular microbiologists with the complementary skills required to make new insights into the molecular processes that underpin bacterial aggregation and biofilm formation. Biofilms are of immense significance in medical, industrial and environmental settings and so the fundamental information gained from this project will have wider relevance to the field of microbiology. An outcome of this proposal will be fundamental knowledge about the production of surface adhesins that will form the basis for rational treatment of disease in the future. Prevention of aggregation and biofilm formation would make bacterial populations more susceptible to conventional antibiotic treatment.Read moreRead less
The evolution of bacterial pathogenesis: a genomic approach. The outcome of this research will be a better understanding of the genes involved with adaptation to particular pathogenic lifestyles. Specifically, genes that are rapidly evolving in selected bacterial pathogens of medical and veterinary importance will be identified using a bioinformatics approach that exploits the existence of multiple closely-related genome sequences. Such genes encode potential new targets for therapeutic interv ....The evolution of bacterial pathogenesis: a genomic approach. The outcome of this research will be a better understanding of the genes involved with adaptation to particular pathogenic lifestyles. Specifically, genes that are rapidly evolving in selected bacterial pathogens of medical and veterinary importance will be identified using a bioinformatics approach that exploits the existence of multiple closely-related genome sequences. Such genes encode potential new targets for therapeutic intervention that provide alternatives in the face of emerging antibiotic resistance. Importantly, the methodology developed in this project is broadly applicable to the study of evolution of bacterial pathogenesis in any background: medical, agricultural or horticultural.Read moreRead less
Molecular mechanisms of pilin glycosylation in Neisseria: a model system for protein glycosylation in bacteria. The disease causing bacteria Neisseria meningitidis and Neisseria gonorrhoeae are important human pathogens. Cell surface structures, called pili, are known to be important in allowing the bacteria to stick to host cells. Genetic and structural studies have identified that the protein subunits, which make up pili, are glycosylated - modified by the addition of sugars. Until recently ....Molecular mechanisms of pilin glycosylation in Neisseria: a model system for protein glycosylation in bacteria. The disease causing bacteria Neisseria meningitidis and Neisseria gonorrhoeae are important human pathogens. Cell surface structures, called pili, are known to be important in allowing the bacteria to stick to host cells. Genetic and structural studies have identified that the protein subunits, which make up pili, are glycosylated - modified by the addition of sugars. Until recently glycosylation of Gram-negative bacterial proteins was not thought to occur, however our recent work with these bacteria, and other groups studying Pseudomonas and Campylobacter, have shown that this process may be widespread. In our previous studies, we have identified and analysed a number of genes involved in pili glycosylation, in bacteria, which make known sugar structures. We have used this information to developed models for how the biochemistry and physiology of the glycosylation system may work. With a well-established structure and many genes already identified, glycosylation in Neisseria represents the best available model system to study this novel and important process. In the proposed study we describe experiments planned to test our models and reveal the molecular detail of this process. This study could lead to major advances in our understanding of this process and, when understood, may have future applications in biotechnology.Read moreRead less
Phasevarions of Haemophilus influenzae: mechanisms and origins of a novel epigenetic system controlling coordinated random switching in expression of multiple genes. Central to the utilisation of biological information is our ability to identify and interpret DNA sequence information from genomes. In bacteria that cause disease, these investigations can identify key aspects of the infectious process or potential components of vaccines or new targets for antibiotics. Our recent work has identifie ....Phasevarions of Haemophilus influenzae: mechanisms and origins of a novel epigenetic system controlling coordinated random switching in expression of multiple genes. Central to the utilisation of biological information is our ability to identify and interpret DNA sequence information from genomes. In bacteria that cause disease, these investigations can identify key aspects of the infectious process or potential components of vaccines or new targets for antibiotics. Our recent work has identified a new genetic system, the 'phasevarion', that mediates random expression of multiple genes. The proposed research aims to advance our understanding of gene expression at the most basic level, revealing how bacteria generate diverse populations to evade environmental and immune stresses, and facilitating improved interpretation and use of DNA sequences for researchers and industry in this field.Read moreRead less
Autotransporter proteins of Escherichia coli. Autoransporters are a novel class of proteins associated with bacterial virulence properties such as adhesion, invasion and biofilm formation. Despite this, limited information is available on their functional role. The aim of this project is to characterize several of the autotransporter proteins from pathogenic E. coli. The likely contribution of these proteins to infection suggests that they are potential targets for strain attenuation and vaccine ....Autotransporter proteins of Escherichia coli. Autoransporters are a novel class of proteins associated with bacterial virulence properties such as adhesion, invasion and biofilm formation. Despite this, limited information is available on their functional role. The aim of this project is to characterize several of the autotransporter proteins from pathogenic E. coli. The likely contribution of these proteins to infection suggests that they are potential targets for strain attenuation and vaccine strain construction. Many of these proteins also mediate bacterial aggregation and are therefore targets for novel drugs that inhibit this process. The project will be carried out with a high profile partner from Denmark and will provide opportunity for travel and technology development. Read moreRead less
Autotransporter proteins of enterohemorrhagic Escherichia coli O157:H7. Escherichi (E.) coli O157:H7 has caused hundreds of outbreaks in the United States and United Kingdom. Although not currently a major problem in Australia, the emergence of E. coli O157:H7 here would have serious implications for our meat and livestock industry. This study will provide important information for the selection of vaccine antigens used to prevent the colonisation of cattle with E. coli O157:H7 and other diarrho ....Autotransporter proteins of enterohemorrhagic Escherichia coli O157:H7. Escherichi (E.) coli O157:H7 has caused hundreds of outbreaks in the United States and United Kingdom. Although not currently a major problem in Australia, the emergence of E. coli O157:H7 here would have serious implications for our meat and livestock industry. This study will provide important information for the selection of vaccine antigens used to prevent the colonisation of cattle with E. coli O157:H7 and other diarrhoeagenic E. coli serotypes. A direct outcome of this will be improved human health, as E. coli O157:H7 can cause life threatening infections in humans. The study will also examine the contribution of specific adhesins to biofilm formation; measures to prevent biofilm formation may reduce the persistence and spread of E. coli O157:H7 in the environment.Read moreRead less
A systems approach to dissect the pathogenicity and host specificity of the Fusarium wilt pathogen, Fusarium oxysporum. The pathogenic fungus Fusarium oxysporum causes wilt disease in many plant species, including many that are important for Australian agriculture. Developing environmentally friendly disease protection strategies against this pathogen requires a clear understanding of infection strategies used by the fungus to invade its host. This project, along with a parallel project in host ....A systems approach to dissect the pathogenicity and host specificity of the Fusarium wilt pathogen, Fusarium oxysporum. The pathogenic fungus Fusarium oxysporum causes wilt disease in many plant species, including many that are important for Australian agriculture. Developing environmentally friendly disease protection strategies against this pathogen requires a clear understanding of infection strategies used by the fungus to invade its host. This project, along with a parallel project in host resistance mechanisms, will provide the basis for development of a world leading platform in mechanisms of fungal pathogenicity and virulence and plant disease resistance/susceptibility. Application of the knowledge gained in this project to other host-pathogen interactions will thereby provide opportunities for improved crop protection and biosecurity.Read moreRead less
Cystine flux and hydrogen peroxide breakdown in reuteri group lactobacilli. We have discovered, and aim to fully dissect a novel function of reuteri group lactobacilli. These microbes inhabit the surfaces of the gastrointestinal and reproductive tracts of humans and are also used as probiotics, and in the dairy industry. This function mediates the production and breakdown of large amounts of hydrogen peroxide, cystine and thiols. These are highly bioactive and affect human cells and other bacter ....Cystine flux and hydrogen peroxide breakdown in reuteri group lactobacilli. We have discovered, and aim to fully dissect a novel function of reuteri group lactobacilli. These microbes inhabit the surfaces of the gastrointestinal and reproductive tracts of humans and are also used as probiotics, and in the dairy industry. This function mediates the production and breakdown of large amounts of hydrogen peroxide, cystine and thiols. These are highly bioactive and affect human cells and other bacteria at the surfaces of the gastrointestinal and reproductive tracts, and thiols are also flavourants in dairy products. Our research will inform the rational development of probiotics, the management and treatment of unpleasant conditions such as Crohn's disease and bacterial vaginosis, and innovation in dairy fermentations.Read moreRead less
The genomics of adaptation in Wolbachia pipientis, an emerging biocontrol agent. Australians are increasingly exposed to insect-transmitted diseases such as dengue fever. Novel biocontrol methods using the bacterium Wolbachia aim to control insect populations to reduce disease transmission. Our research will be the first to investigate genomic variation and the process of adaptation to new insect hosts in Wolbachia. The novel data and understanding of evolutionary processes we generate will be c ....The genomics of adaptation in Wolbachia pipientis, an emerging biocontrol agent. Australians are increasingly exposed to insect-transmitted diseases such as dengue fever. Novel biocontrol methods using the bacterium Wolbachia aim to control insect populations to reduce disease transmission. Our research will be the first to investigate genomic variation and the process of adaptation to new insect hosts in Wolbachia. The novel data and understanding of evolutionary processes we generate will be critical for screening bacterial biocontrol candidates and designing biocontrol release strategies. It will also strengthen the position of Australian research as a world-leader in the fusion of post-genomics and applied microbiology. Read moreRead less
The molecular biology and biochemistry of bacterial manganese oxidation. This project will further the understanding of bacterial manganese (Mn2+) oxidation. A multi-disciplinary approach will be used to further investigate the genetics and biochemistry of the Mn2+-oxidising systems of Pseudomonas putida, Leptothrix sp. and Pedomicrobium sp. This work will focus in particular on comparing the Mn2+-oxidising systems from unrelated bacteria. A combination of molecular biology, protein biochemis ....The molecular biology and biochemistry of bacterial manganese oxidation. This project will further the understanding of bacterial manganese (Mn2+) oxidation. A multi-disciplinary approach will be used to further investigate the genetics and biochemistry of the Mn2+-oxidising systems of Pseudomonas putida, Leptothrix sp. and Pedomicrobium sp. This work will focus in particular on comparing the Mn2+-oxidising systems from unrelated bacteria. A combination of molecular biology, protein biochemistry and spectroscopy will be used. This will be the first time that the enzymes of bacterial Mn2+-oxidation will have been characterised in such detail and will lead to a greater understanding of the process of bacterial manganese oxidation.Read moreRead less