Molecular characterisation of hypervirulence and the infectious cycle in Clostridium difficile. Gut diseases caused by the bacterium Clostridium difficile are a significant animal and public health problem in Australia and many other countries. This project will allow us to understand how this bacterium causes disease, leading to the development of much needed preventative and treatment strategies for animals and human patients.
Discovery Early Career Researcher Award - Grant ID: DE200100111
Funder
Australian Research Council
Funding Amount
$373,097.00
Summary
Replication and transfer of novel plasmid classes in Acinetobacter. The project aims to reveal basic biology of plasmids found in Acinetobacter baumannii. A. baumannii is a bacterial pathogen that can rapidly acquire resistance to antibiotics, including last-resort antibiotics. In modern strains, acquisition is often mediated by plasmids. On the basis of DNA sequencing data, A. baumannii plasmids are likely to function differently to well-studied plasmids. However, surprisingly little experiment ....Replication and transfer of novel plasmid classes in Acinetobacter. The project aims to reveal basic biology of plasmids found in Acinetobacter baumannii. A. baumannii is a bacterial pathogen that can rapidly acquire resistance to antibiotics, including last-resort antibiotics. In modern strains, acquisition is often mediated by plasmids. On the basis of DNA sequencing data, A. baumannii plasmids are likely to function differently to well-studied plasmids. However, surprisingly little experimental work has been done to evidence this. By combining microbiological and bioinformatics approaches the project expects to generate new knowledge on the mechanisms of replication and transfer of A. baumannii plasmids. This may lead to new targets for strategies to slow and track the spread of antibiotic resistance.Read moreRead less
A link between antibiotic resistance and bacterial sporulation. This project aims to define the sporulation process in the bacterium Clostridium difficile, and advance our understanding of a link between antibiotic use and sporulation. To survive in hostile environments, some bacteria produce a dormant and resilient cell form called a spore which can survive for many years in unfavourable environments, but our understanding of how this process occurs is limited. This project will provide a deepe ....A link between antibiotic resistance and bacterial sporulation. This project aims to define the sporulation process in the bacterium Clostridium difficile, and advance our understanding of a link between antibiotic use and sporulation. To survive in hostile environments, some bacteria produce a dormant and resilient cell form called a spore which can survive for many years in unfavourable environments, but our understanding of how this process occurs is limited. This project will provide a deeper understanding of the sporulation process and the long-lasting detrimental impact of antibiotic use. The project expects to provide economic benefits, reduce environmental microbial contamination and contribute to better health of animals and humans.Read moreRead less
Bacterial poly-histidine triad proteins. The poly-histidine triad (Pht) proteins are a poorly characterised family of surface proteins expressed by the genus Streptococcus and other Gram-positive genera. Recent studies suggest an important role for Pht proteins in survival of these bacteria in low zinc (Zn) environments. The project hypothesis is that Pht proteins specifically recruit Zn from the extracellular environment and somehow make it available to ATP binding cassette (ABC) transport syst ....Bacterial poly-histidine triad proteins. The poly-histidine triad (Pht) proteins are a poorly characterised family of surface proteins expressed by the genus Streptococcus and other Gram-positive genera. Recent studies suggest an important role for Pht proteins in survival of these bacteria in low zinc (Zn) environments. The project hypothesis is that Pht proteins specifically recruit Zn from the extracellular environment and somehow make it available to ATP binding cassette (ABC) transport systems located in the bacterial plasma membrane, beneath the cell wall, facilitating Zn uptake by the bacterium. The aim of this project is to conduct comprehensive molecular characterization of the interactions between Pht proteins, Zn and ABC transporters, and the role of the histidine triad motifs in these interactions.Read moreRead less
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
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
A comparative genomics approach to understanding host-endosymbiont interactions. Australia's unique ecosystems are vulnerable to invasion by exotic pests that threaten agriculture and human health. The bacterial symbiont Wolbachia is found in many major pests of agricultural and medical importance. Our results will give insights into how Wolbachia spreads into host populations and improve its use as a tool to impair insect transmission of disease, e.g. as an agent to carry genes into an insect p ....A comparative genomics approach to understanding host-endosymbiont interactions. Australia's unique ecosystems are vulnerable to invasion by exotic pests that threaten agriculture and human health. The bacterial symbiont Wolbachia is found in many major pests of agricultural and medical importance. Our results will give insights into how Wolbachia spreads into host populations and improve its use as a tool to impair insect transmission of disease, e.g. as an agent to carry genes into an insect population that limit disease transmission. Our results will also make fundamental contributions to understanding host-parasite evolution, host-parasite communication, and insect developmental processes, and will be of interest to a large international community of researchers in this field. Read moreRead less
The host specificity of bacterial pathogens. The vast majority of microorganisms that cause diseases in animals are host specific. In other words, they cause disease exclusively in a particular animal species, but are harmless for others. Despite considerable recent advances in our understanding of the mechanisms used by microorganisms in general to cause disease, in most cases the underlying basis of host-specificity is not known. In this project, we will use two animal pathogens, rabbit-spe ....The host specificity of bacterial pathogens. The vast majority of microorganisms that cause diseases in animals are host specific. In other words, they cause disease exclusively in a particular animal species, but are harmless for others. Despite considerable recent advances in our understanding of the mechanisms used by microorganisms in general to cause disease, in most cases the underlying basis of host-specificity is not known. In this project, we will use two animal pathogens, rabbit-specific enteropathogenic E. coli and the closely related bacterium, Citrobacter rodentium, which specifically infect rabbits and mice respectively, to investigate the molecular basis of host specificity.Read moreRead less
The biology of integrons and their role in bacterial adaptation. Bacteria evolve in ways that animals and plants do not. One of the tools available is the ability to share genes amongst individuals in a community. One example of this is the very rapid spread of antibiotic resistance genes in pathogens. Here we will be studying a genetic element that greatly contributes to this horizontal spread of genes. This will lead to a better understanding of how bacteria work, the direct benefits of whic ....The biology of integrons and their role in bacterial adaptation. Bacteria evolve in ways that animals and plants do not. One of the tools available is the ability to share genes amongst individuals in a community. One example of this is the very rapid spread of antibiotic resistance genes in pathogens. Here we will be studying a genetic element that greatly contributes to this horizontal spread of genes. This will lead to a better understanding of how bacteria work, the direct benefits of which includes the discovery of new pathways and genes for the biotechnology industry and greater understanding of how bacteria cause disease in us, other animals and in commercial crops.Read moreRead less
A functional genomic approach for understanding metal ion adaptation in marine cyanobacteria. Unicellular marine cyanobacteria constitute 20-40% of total marine chlorophyll biomass and carbon fixation, and hence significantly impact the global carbon cycle and are very relevant to combating global warming. This research will reveal some of the major mechanisms by which marine cyanobacteria have adapted to metal levels in coastal and oligotrophic environments. Thus these results will help us und ....A functional genomic approach for understanding metal ion adaptation in marine cyanobacteria. Unicellular marine cyanobacteria constitute 20-40% of total marine chlorophyll biomass and carbon fixation, and hence significantly impact the global carbon cycle and are very relevant to combating global warming. This research will reveal some of the major mechanisms by which marine cyanobacteria have adapted to metal levels in coastal and oligotrophic environments. Thus these results will help us understand the distribution and diversity of these organisms in relation to global primary productivity. They will also lead to the development of more robust biomarkers for metal stress and pollution in coastal environments.Read moreRead less