Attenuation mechanism of Brucella melitensis M5-10,implications for vaccine development and differential diagnosis

作     者：Yuanqiang ZHENG Yanchun SHI Chang AN Ruisheng LI Dongjun LIU Yuehua KE Kairong MAO Mingjuan YANG Zeliang CHEN Shorgan BOU 

作者机构：National Research Center for Animal Transgenic BiotechnologyInner Mongolia UniversityHohhot 010021China Inner Mongolia Key Laboratory of Molecular BiologyInner Mongolia Medical UniversityHohhot 010058China Animal Laboratory Center302 Hospital of PLABeijing 100039China Institute of Disease Control and PreventionAcademy of Military Medical SciencesBeijing 100071China China Institute of Veterinary Drug ControlCenter for Veterinary Drug EvaluationMinistry of AgricultureBeijing 100081China College of MedicineShihezi UniversityShihezi 832003China 

出 版 物：《Frontiers of Agricultural Science and Engineering》 (农业科学与工程前沿（英文版）)

年 卷 期：2014年第1卷第4期

页      面：331-340页

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by grants from National Twelfth Five-Year Plan for Science&Technology Support of China(2014BAI13B03) National Natural Science Foundation of China(81460248,81260457,81271899,31272592,81071320) Inner Mongolia Natural Science Funds(2013MS1138,2012MS1121,2011MS1110) Beijing Natural Science Foundation(6122030,7132153) Inner Mongolia Science&Technology Plan(20120101,20120402,20110502) the National Key Program for Infectious Diseases of China(2013ZX10004-203,2013ZX10004-217-002,2013ZX10004805-006) 

主　　题：Brucella live attenuated vaccine attenuation differential diagnosis 

摘      要：Brucellosis is a worldwide *** is the most efficient means to prevent and control *** current licensed attenuated vaccines for animal use were developed by sequential passage in nonnatural hosts that decreased virulence in its original *** attenuation mechanism of these strains remains largely *** the present study,we sequenced the genome of Brucella melitensis vaccine strain *** analysis showed that a large number of genetic changes occurred in the vaccine strains.A total of 2854 genetic polymorphic sites,including 2548 SNP,241 INDEL and 65 MNV were *** the 2074 SNPs in coding regions,1310(63.2%)were non-synonymous *** number,percent and N/S ratios were disproportionally distributed among the cog *** polymorphic sites were identified in genes of the virB operon,flagella synthesis,and virulence regulating *** data indicate that changes in some cog categories and virulence genes might result in the *** attenuation mechanisms also have implications for screening and development of new vaccine *** genetic changes in the genome represent candidate sites for differential diagnosis between these vaccine strains and other virulence *** analysis of virulence genes showed that expression of dnaK,vjbR were reduced in M5-10 strain when compared with that in 16M.A duplex PCR targeting virB6 and dnaK was successfully used to differentiate between M5-10 and the virulent 16M *** genome re-sequencing technique represents a strong strategy not only for evaluation of vaccines,but also for development of new vaccines.