中国El Tor生物型霍乱弧菌流行株中非溶血变异菌株分布及进化特征  

Distribution and evolutionary characteristics of non-hemolytic mutant of El Tor biotype epidemic Vibrio cholerae in China

作　　者：范宇峰 赵林 卢昕[1] 李旭[1] 孙惠惠 王嘉正 刘鸣 李杰[1] 逄波[1] 阚飙[1] Fan Yufeng;Zhao Lin;Lu Xin;Li Xu;Sun Huihui;Wang Jiazheng;Liu Ming;Li Jie;Pang Bo;Kan Biao(National Institute for Communicable Disease Control and Precention,Beijing 102206,China;The First Hospital Affiliated with Shandong First Medical University,Jinan 250014,Shandong,China)

机构地区：[1]中国疾病预防控制中心传染病预防控制所,北京102206 [2]山东第一医科大学第一附属医院,山东济南250014

出　　处：《疾病监测》2019年第6期489-494,共6页Disease Surveillance

基　　金：国家重点基础研究发展规划(No.2015CB554201)~~

摘　　要：目的分析第7次霍乱大流行期间中国O1群El Tor型霍乱弧菌流行菌株中非溶血变异菌株的流行分布特征以及进化特征。方法选择1961年以来不同霍乱流行期的O1群El Tor型产毒菌株,测定溶血表型并分析其时间分布特点。比较菌株溶血素基因hlyA的序列变异及不同序列型的分布,构建这些菌株的核心基因组进化树,分析非溶血株在进化分支中的分布及克隆化特征。结果在第7次霍乱大流行的中国霍乱流行中,溶血素基因hlyA在第1次流行高峰期后,出现了明显的序列型转换。非溶血株主要出现在始于20世纪70年代的第2次流行中,并成为多见的变异型。非溶血菌株分布在不同流行期和流行克隆中,没有形成单一的克隆化。但部分非溶血菌株克隆引起数年的流行扩散。结论 O1群El Tor型菌株的非溶血变异独立于基因组逐年累积的克隆进化,很可能是一种随机性较强的变异。Objective To analyze the distribution and evolutionary characteristics of the non-hemolytic mutant of El Tor biotype strain of Vibrio cholerae O1 in China during the 7^th global cholera pandemic.Methods Toxigenic El Tor biotype strains of V.cholerae in different cholera pandemic periods since 1961 were selected for hemolytic phenotype test and whole genome sequencing.The temporal distribution of the non-hemolytic mutant was displayed.The sequence variation in hlyA gene was illustrated.ML tree was constructed based on the SNPs in the non-repetitive and non-recombinant genome regions of230 El Tor biotype strains of V.cholerae O1 isolated in China since 1961.The distribution of the non-hemolytic mutants was mapped on the ML tree.Results During the 7^th cholera pandemic,there was an obvious sequence type conversion of the hemolysin gene hlyA in the strains detected in China after the first phase of pandemic.The non-hemolytic mutants emerged after the first phase of pandemic and became a common type in the 2^nd pandemic in 1970 s.The non-hemolytic mutant dispersed in the 2^nd,3rd pandemic and the inter-pandemic periods.However,certain clones of non-hemolytic mutant spread for several years.Conclusion The evolution of hlyA gene was independent of that of the whole genome in the 7^th cholera pandemic,which might be a random mutation.The results showed the role of hemolytic phenotype in the biotyping of epidemic strains.

关 键 词：霍乱弧菌 霍乱溶血素 hlyA基因 生物型 序列型 单核苷酸多态性分析 

分 类 号：R378.3[医药卫生—病原生物学]