sequencing and genetic variation of multidrug resistance plasmids in klebsiella pneumoniae测序和基因变异的多药耐药性肺炎克雷伯菌质粒.pdfVIP

Sequencing and Genetic Variation of Multidrug Resistance Plasmids in Klebsiella pneumoniae 1,2. 1,3. 1 1 1 1 1 Fangqing Zhao , Jie Bai , Jinyu Wu , Jing Liu , Mingming Zhou , Shilin Xia , Shanjin Wang , 1 1 1 1 1 1 1 1 Xiaoding Yao , Huiguang Yi , Meili Lin , Shengjie Gao , Tieli Zhou , Zuyuan Xu , Yuxin Niu *, Qiyu Bao * 1 Institute of Biomedical Informatics, Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical College, Wenzhou, China, 2 Center for Comparative Genomics and Bioinformatics, The Pennsylvania State University, University Park, Pennsylvania, United States of America, 3 Department of Microbiology and Microbial Engineering, School of Life Sciences, Fudan University, Shanghai, China Abstract Background: The development of multidrug resistance is a major problem in the treatment of pathogenic microorganisms by distinct antimicrobial agents. Characterizing the genetic variation among plasmids from different bacterial species or strains is a key step towards understanding the mechanism of virulence and their evolution. Results: We applied a deep sequencing approach to 206 clinical strains of Klebsiella pneumoniae collected from 2002 to 2008 to understand the genetic variation of multidrug resistance plasmids, and to reveal the dynamic change of drug resistance over time. First, we sequenced three plasmids (70 Kb, 94 Kb, and 147 Kb) from a clonal strain of K. pneumoniae using Sanger sequencing. Using the Illumina sequencing technology, we obtained more than 17 million of short reads from two pooled plasmid samples. We mappe