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Genetics & Virulence
This group is investigating the genetic and molecular basis of bacteria disease pathogenesis by studying the production and biochemistry of virulence factors and the underlying genetics and specific genetic control of these molecules. The group has been extensively involved in investigating the important health care-associated antimicrobial-resistant pathogen Clostridium difficile. The group was the first to develop methodologies for the genetic analysis of this bacterium and was involved in the completion of its complete genome sequence. The group, in collaboration with the Sanger Institute, has recently received significant funding from Wellcome Trust to use a metagenomics approach to characterise all bacterial genomes in the oral cavity i.e. the oral metagenome. The C. difficile genome information and genetic technology is currently being used to determine the roles of various gene products (i.e. toxins and adhesions), in disease pathogenesis, complementing the work being undertaken by the Cellular Microbiology group. They have also identified novel virulence factors of the other important health care-associated antimicrobial-resistant pathogen Staphylococcus aureus [MRSA], as well as important oral pathogens involved in periodontal disease (Aggregatibacter (formally Actinobacillus) actinomycetemcomitans [Aa]), and caries (Streptococcus sanguis and S. mutans). Regulation of virulence factor expression by these organisms is also being investigated. In collaboration with the Antimicrobial strategies and resistance group, the molecular basis of the spread of antimicrobial resistance by conjugative transposons has been investigated. These elements are ubiquitous in bacteria and have the ability to transfer between unrelated bacterial species. The group has shown that these elements are modular - having conjugation, regulatory, recombinogenic and auxiliary regions (which often contain antimicrobial -resistance genes). The mechanism by which these elements integrate and excise from genomes has been investigated - as this could lead to the development of adjuvant therapies to prevent the spread of antimicrobial resistance and also provide useful tools for the genetic manipulation of a broad range of bacteria.
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