Genetic tools for analyzing B. pseudomallei virulence

描述（由申请人提供）：拟议研究的目标是开发B基因操作的新方法。假鼻疽待开发的工具应使其更容易创建靶向突变和多个突变株，以确定未知的突变不是由于转座子插入，进行互补分析的任何区域的基因组，并产生和定义菌株与杂交基因组。拟议的研究与R21资助机制的探索/开发性质一致，因为其旨在制定对实现计划公告（PA-03-080）的目标具有潜在广泛影响的程序，例如识别B。研究人员正在研究类鼻疽假单胞菌毒力决定因素并分析它们如何发挥作用，确定先天性和获得性抗生素耐药机制，鉴定宿主识别的细菌抗原，并创建活疫苗株。

DESCRIPTION (provided by applicant): The goal of the proposed research is to develop new methodologies for the genetic manipulation of B. pseudomallei. The tools to be developed should make it easier to create targeted mutations and multiple mutant strains, to identify unknown mutations not due to transposon insertion, to carry out complementation analysis for any region of the genome, and to generate and define strains with hybrid genomes. The proposed research is consistent with the exploratory/development nature of the R21 funding mechanism because it is designed to develop procedures with potentially broad impact on reaching the goals of the program announcement (PA-03-080), such as identifying B. pseudomallei virulence determinants and analyzing how they function, specifying innate and acquired antibiotic resistance mechanisms, identifying bacterial antigens recognized by the host, and creating live vaccine strains.