鼠疫菌是导致鼠疫的病原体，历史上曾致三次世界大流行，是改变人类文明进程的重要传染病。鼠疫菌与其祖先假结核菌比，进化了经蚤传播能力和高致病性。前期研究表明，它们与两个新获得质粒（pPCP1和pPMT1）有关。但其分子基础仍未被揭示。本研究基于“质粒获得及其相互作用和对基因调控网络的重塑在鼠疫菌致病性和传播性获得中发挥着关键作用”的科学假设，利用动物模型比较质粒缺失株（pCD1+、pMT1+、pPCP1+、pCD1+-pMT1+、pCD1+-pPCP1+和pMT1+-pPCP1+）和野生株（pCD1+-pMT1+-pPCP1+）的致病性变化，研究外源质粒对鼠疫菌致病性的影响及其分子机制；并研究新获得质粒编码的调控子和sRNA对基因调控网络重塑及其在致病性和传播性中作用的分子机制。从而探究 “质粒获得与基因调控重塑决定鼠疫菌致病性和传播性的分子基础”这一命题。

Yersinia pestis is the causative agent of plague, which caused three pandemics in human history, and plague is an important infectious disease that changing the path of human civilization. Compared with its ancestor Yersinia pseudotuberculosis, Y. pestis acquired transmissibility by flea and high pathogenicity. Previous studies demonstrated that these two newly emerging features were related to two newly acquired plasmids (pPCP1 and pMT1). However, its molecular mechanism has not been elucidated. This project is based on the scientific hypothesis that acquisition of plasmids and their interactions, and their roles in remodeling of genetic regulation system played critical roles during Y. pestis evolution. The palsmid-cured strains (pCD1+、pMT1+、pPCP1+、pCD1+-pMT1+、pCD1+-pPCP1+和pMT1+-pPCP1+) and wild type strain (pCD1+-pMT1+-pPCP1+) will be compared in terms of pathogenicity using animal model and study on molecular basis for the role of acquired plasmids on pathogenicity. The role of genetic regulation system remodeling by newly acquired regulators and sRNAs and their molecular mechanisms in determining pathogenicity and transmissibility of Y. pestis will also be elucidated using different kind of methods. Therefore, the objective of this project, molecular basis of plasmids acquisition and genetic regulation remodeling in determining pathogenicity and transmissibility, could be revealed. Our laboratory has focused on genomics, evolution and pathogenicity of Yersinia pestis for more than 10 years and has laid a solid foundation for this project. The success of this project will promote our understanding on the evolutionary process of Y. pestis, and also provide novel idea for studying other bacterial pathogens.