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

耶尔森氏菌在微生物学史上占有重要地位。鼠疫耶尔森氏菌，鼠疫的病原体，在周期性的大流行中夺去了数百万人的生命，对人类历史和文明的影响可能比任何其他细菌都要大。Y.小肠结肠炎和Y.假结核（Y.最近进化出的鼠疫）也是适应性很强的主要人类病原体，它们已经进化出复杂的调节网络，便于从土壤和水迁移到昆虫和动物宿主。三种致病性耶尔森氏菌都具有第三型分泌（T3 S）系统，该系统通过称为注射体的大分子针状结构将效应蛋白递送到真核细胞的胞质溶胶中，引起宿主细胞信号系统的破坏，触发细胞骨架重排并诱导凋亡。注射体的所有结构成分，沿着效应物都编码在一个毒力质粒上，其表达受温度调节。通过N-酰基高丝氨酸内酯依赖的细胞间通讯系统（称为群体感应（QS））协调群体依赖行为。在假结核耶尔森氏菌中，QS控制几种毒力相关的表型，包括线虫线虫表面生物膜的形成、游泳运动、N乙酰氨基葡萄糖代谢、细胞聚集以及在本项目背景下至关重要的T3 S系统表达的调节。最近的观察还表明，T3 S毒力质粒在不断扩大的细菌群体中的保留也是受QS控制的。在这些最近的成功的基础上，该项目旨在进一步详细研究QS和毒力质粒保留之间的调节关系的性质。本项目将以Y. pseudotuberculosis和Y.鼠疫，并将使用传统的微生物学技术与复杂的分子遗传技术相结合的混合物，以及使用模式生物，如C。elegans、印鼠客蚤（Xenopsylla cheopis）和人体虱（Pediculus humanus humanus）的毒力质粒滞留的研究。

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.