Whole-Genome Phylogenomic Heterogeneity of Neisseria gonorrhoeae Isolates with Decreased Cephalosporin Susceptibility Collected in Canada between 1989 and 2013
Whole-Genome Phylogenomic Heterogeneity of Neisseria gonorrhoeae Isolates with Decreased Cephalosporin Susceptibility Collected in Canada between 1989 and 2013
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DOI：
10.1128/jcm.02589-14
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发表时间：
2015-01-01
影响因子：
9.4
通讯作者：
Mulveya, Michael R.
中科院分区：
文献类型：
--
作者：
Demczuk, Walter;Lynch, Tarah;Mulveya, Michael R.
采用大规模、全基因组比较的方法，对具有高水平头孢菌素MIC的加拿大淋病奈瑟菌分离株进行了基因组流行病学研究，以研究菌株间的关联性和动力学。虽然目前的分型方法在追踪淋病的短链传播方面已经非常成功，但研究高度克隆谱系的时间进化关系和地理传播需要提高分辨率，只有通过全基因组测序(WGS)才能实现。系统发育聚类分析将169个加拿大菌株分为12个不同的分支。虽然有些淋球菌多抗原序列类型(NG-MAST)与特定的系统发育分支或亚分支一致，但其他序列类型(ST)和密切相关的ST组广泛分布于各分支之间。20世纪90年代，在加拿大的一组不同菌株中出现了对超广谱头孢菌素(ESC-DS)敏感性的降低，其中包括各种非花叶Pena等位基因，其次是2000/2001年的Pena Mosaic X等位基因，然后是2007年的ST1407菌株，其Pena Mosaic XXXIV等位基因。5个遗传上不同的ESC-DS谱系与大豆花叶X、XXXV和XXXIV等位基因以及非花叶XII和XIII等位基因相关。在5株23S rRNA C2599T或A2143G突变的菌株中发现对阿奇霉素具有协同耐药的ESC-DS。随着与WGS相关的成本下降和分析工具的简化，WGS可以提供对菌株动态的更全面的了解，促进流行病学研究以更好地解决社会网络，并改进监测以优化淋病感染的治疗。
A large-scale, whole-genome comparison of Canadian Neisseria gonorrhoeae isolates with high-level cephalosporin MICs was used to demonstrate a genomic epidemiology approach to investigate strain relatedness and dynamics. Although current typing methods have been very successful in tracing short-chain transmission of gonorrheal disease, investigating the temporal evolutionary relationships and geographical dissemination of highly clonal lineages requires enhanced resolution only available through whole-genome sequencing (WGS). Phylogenomic cluster analysis grouped 169 Canadian strains into 12 distinct clades. While some N. gonorrhoeae multiantigen sequence types (NG-MAST) agreed with specific phylogenomic clades or subclades, other sequence types (ST) and closely related groups of ST were widely distributed among clades. Decreased susceptibility to extended-spectrum cephalosporins (ESC-DS) emerged among a group of diverse strains in Canada during the 1990s with a variety of nonmosaic penA alleles, followed in 2000/2001 with the penA mosaic X allele and then in 2007 with ST1407 strains with the penA mosaic XXXIV allele. Five genetically distinct ESC-DS lineages were associated with penA mosaic X, XXXV, and XXXIV alleles and nonmosaic XII and XIII alleles. ESC-DS with coresistance to azithromycin was observed in 5 strains with 23S rRNA C2599T or A2143G mutations. As the costs associated with WGS decline and analysis tools are streamlined, WGS can provide a more thorough understanding of strain dynamics, facilitate epidemiological studies to better resolve social networks, and improve surveillance to optimize treatment for gonorrheal infections.