Further insights into the mechanisms of virulence plasmid stability and control in Yersinia spp

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The genus Yersinia occupies a prominent place in the history of microbiology. Yersinia pestis, thecausative agent of plague has claimed millions of lives in periodic pandemics, influencing humanhistory and civilisation possibly to a greater extent than any other bacterium. Y. enterocolitica andY. pseudotuberculosis (from which Y. pestis recently evolved) are also highly adaptable primaryhuman pathogens which have evolved sophisticated regulatory networks that facilitate migrationfrom soil and water to insects and animal hosts. All three pathogenic Yersinia possess a type threesecretion (T3S) system which delivers effector proteins into the cytosol of eukaryotic cells througha macromolecular needle-like structure known as the injectisome causing disruption of host cellsignalling systems ,triggering cytoskeletal rearrangement and inducing apoptosis. All the structuralcomponents of the Injectisome, along with the effectors are encoded on a virulence plasmid whereexpression is regulated by temperature.Yersinia spp. co-ordinate population-dependent behaviour through an N-acylhomoserine lactonedependentcell-to-cell communication system referred to as quorum sensing (QS) . In Y.pseudotuberculosis, QS governs several virulence related phenotypes including biofilm formationon the surface of the nematode worm Caenorhabditis elegans, swimming motility, Nacetylglucosaminemetabolism, cell aggregation and crucially in the context of this project, theregulation of the expression of the T3S system. Recent observations have also revealed that theregulation of T3S virulence plasmid retention across an expanding bacterial population is also QScontrolled. Building on these recent successes this project aims to examine in further detail thenature of the regulatory relationships between QS and virulence plasmid retention. The project willfocus on Y. pseudotuberculosis and Y. pestis and will use a mixture of traditional microbiologytechniques coupled to sophisticated molecular genetic techniques as well as using modelorganisms such as C. elegans, Xenopsylla cheopis (rat flea) and Pediculus humanus humanus(human body louse) to investigate how virulence plasmid retention is regulated by QS in theenvironment and in the host.