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

The genus Yersinia occupies a prominent place in the history of microbiology. Yersinia pestis, the
causative agent of plague has claimed millions of lives in periodic pandemics, influencing human
history and civilisation possibly to a greater extent than any other bacterium. Y. enterocolitica and
Y. pseudotuberculosis (from which Y. pestis recently evolved) are also highly adaptable primary
human pathogens which have evolved sophisticated regulatory networks that facilitate migration
from soil and water to insects and animal hosts. All three pathogenic Yersinia possess a type three
secretion (T3S) system which delivers effector proteins into the cytosol of eukaryotic cells through
a macromolecular needle-like structure known as the injectisome causing disruption of host cell
signalling systems ,triggering cytoskeletal rearrangement and inducing apoptosis. All the structural
components of the Injectisome, along with the effectors are encoded on a virulence plasmid where
expression is regulated by temperature.
Yersinia spp. co-ordinate population-dependent behaviour through an N-acylhomoserine lactonedependent
cell-to-cell communication system referred to as quorum sensing (QS) . In Y.
pseudotuberculosis, QS governs several virulence related phenotypes including biofilm formation
on the surface of the nematode worm Caenorhabditis elegans, swimming motility, Nacetylglucosamine
metabolism, cell aggregation and crucially in the context of this project, the
regulation of the expression of the T3S system. Recent observations have also revealed that the
regulation of T3S virulence plasmid retention across an expanding bacterial population is also QS
controlled. Building on these recent successes this project aims to examine in further detail the
nature of the regulatory relationships between QS and virulence plasmid retention. The project will
focus on Y. pseudotuberculosis and Y. pestis and will use a mixture of traditional microbiology
techniques coupled to sophisticated molecular genetic techniques as well as using model
organisms 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 the
environment and in the host.