Genomic Epidemiology and Molecular Resistance Mechanisms of Azithromycin-Resistant Neisseria gonorrhoeae in Canada from 1997 to 2014
Genomic Epidemiology and Molecular Resistance Mechanisms of Azithromycin-Resistant Neisseria gonorrhoeae in Canada from 1997 to 2014
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DOI：
10.1128/jcm.03195-15
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发表时间：
2016-05-01
影响因子：
9.4
通讯作者：
Mulvey, Michael R.
中科院分区：
文献类型：
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作者：
Demczuk, Walter;Martin, Irene;Mulvey, Michael R.
淋病奈瑟菌菌株对头孢菌素和阿奇霉素（AZM）耐药（AZM（r））的敏感性降低，这代表了无法治疗的淋病感染对公共卫生的威胁。通过全基因组测序的基因组流行病学被用来描述AZM（r）菌株的出现、传播和扩散。对213株AZM（r）和23株AZM敏感株N.对1989年至2014年在加拿大收集的淋病分离株进行了测序。核心单核苷酸多态性（SNP）分析将246株分离株分为13个谱系。在5个系统发育不同的分离株中发现了高水平的AZM（r）（MIC>= 256 μ g/ml），所有这些分离株在所有四个23 S rRNA等位基因中都具有A2059 G突变（大肠杆菌编号）。2009年收集的一株高水平AZM（r）的分离株同时对头孢曲松的敏感性降低（MIC = 0.125 μ g/ml）。C2611 T突变的23 S rRNA等位基因数量增加（E.大肠杆菌编号）赋予低至中等水平的AZM（r）（MIC分别为2至4和8至32 μ g/ml）。低水平AZM（r）也与mtrR启动子突变有关，包括-35A缺失和脑膜炎奈瑟菌样序列的存在。地理和时间的系统发生聚类表明，新兴的AZM（r）菌株独立出现，然后可以通过当地的性网络在一个地区迅速克隆扩张。
The emergence of Neisseria gonorrhoeae strains with decreased susceptibility to cephalosporins and azithromycin (AZM) resistance (AZM(r)) represents a public health threat of untreatable gonorrhea infections. Genomic epidemiology through whole-genome sequencing was used to describe the emergence, dissemination, and spread of AZM(r) strains. The genomes of 213 AZM(r) and 23 AZM-susceptible N. gonorrhoeae isolates collected in Canada from 1989 to 2014 were sequenced. Core single nucleotide polymorphism (SNP) phylogenomic analysis resolved 246 isolates into 13 lineages. High-level AZM(r) (MICs >= 256 mu g/ml) was found in 5 phylogenetically diverse isolates, all of which possessed the A2059G mutation (Escherichia coli numbering) in all four 23S rRNA alleles. One isolate with high-level AZM(r) collected in 2009 concurrently had decreased susceptibility to ceftriaxone (MIC = 0.125 mu g/ml). An increase in the number of 23S rRNA alleles with the C2611T mutations (E. coli numbering) conferred low to moderate levels of AZM(r) (MICs = 2 to 4 and 8 to 32 mu g/ml, respectively). Low-level AZM(r) was also associated with mtrR promoter mutations, including the -35A deletion and the presence of Neisseria meningitidis-like sequences. Geographic and temporal phylogenetic clustering indicates that emergent AZM(r) strains arise independently and can then rapidly expand clonally in a region through local sexual networks.