Genetic clustering and virulence of Y. pestis strains

描述（由申请人提供）：Y。鼠疫菌是在世纪之交传入美国的，因此，美国Y.鼠疫分离株相对有限。相比之下，Y.几个世纪以来，鼠疫在前苏联（FSU）的许多国家一直是地方性的，许多Y。在FSU的文献中与鼠疫相关的出版物强烈表明FSU的Y。鼠疫菌株在遗传上比美国的Y.鼠疫分离物。了解菌株之间的遗传和毒力性状差异将是至关重要的，在先进的工具和战略，以处理可能的Y。在美国和其他地方发生的与鼠疫有关的生物恐怖袭击。因此，我们建议开始对Y.鼠疫菌株从几个地方性地点的鼠疫在前苏联的高加索地区，并开始划定的关键差异之间的遗传组成和毒力性状的Y。FSU和其他地方的鼠疫菌株。本研究的主要目的是：（1）研究Y染色体的变异性;鼠疫菌菌株的FSU，并进行比较MLST，PFGE，和MLVA分析的Y。（2）鉴定FSU的鼠疫菌质粒组成;鼠疫分离株，并进行基于核苷酸序列的分析，选择质粒和染色体编码的毒力基因，（3）开始阐明流行和表达模式的主要毒力基因在FSU的Y。R21资助机制非常适合支持我们提出的研究，它将帮助我们产生有关Y的遗传组成和基因表达模式的重要信息/初始数据。鼠疫分离株以前无法获得的FSU以外的研究人员，目前的信息很少。生成的数据也将在我们设计适当的未来研究中发挥关键作用，并在扩大我们的Y。马里兰州医学院的鼠疫研究项目。

DESCRIPTION (provided by applicant): Y. pestis, the etiologic agent of plague, was introduced into the United States at the turn of the 20th century; therefore, the genetic and phenotypic diversity of American Y. pestis isolates is relatively limited. In contrast, Y. pestis has been endemic in many countries of the former Soviet Union (FSU) for many centuries and numerous Y. pestis-related publications in the FSU's literature strongly suggest that the FSU's Y. pestis strains are genetically more diverse than are American Y. pestis isolates. Understanding the genetic and virulence trait differences among strains will be of critical importance during the development of advanced tools and strategies to deal with possible Y. pestis-related bioterrorism attacks in the USA and elsewhere. Therefore, we propose to begin a comprehensive characterization of Y. pestis strains from several endemic loci of plague in the FSU's Caucasus region, and to begin delineating the critical differences between the genetic make-up and virulence traits of Y. pestis strains from the FSU and elsewhere. Three specific aims will be addressed: (1) Characterize the genomic variability of Y. pestis strains from the FSU, and perform comparative MLST, PFGE, and MLVA analyses for Y. pestis fingerprinting, (2) Characterize the plasmid compositions of the FSU's Y. pestis isolates, and perform nucleotide sequence-based analyses of selected plasmid- and chromosomally-encoded virulence genes, and (3) Begin elucidating the prevalence and the expression patterns of major virulence genes in the FSU's Y. pestis isolates, using microarrays and RT PCR The R21 grant mechanism is ideally suited for supporting our proposed studies, and it will help us to generate important information/initial data concerning the genetic make-up and gene expression patterns of Y. pestis isolates previously unavailable to investigators outside the FSU, and for which very little information is currently available. The generated data will also play a critical role in our designing appropriate future studies, and in expanding our Y. pestis research program at the University of Maryland School of Medicine.