Sustained transmission of high-level azithromycin-resistant Neisseria gonorrhoeae in England: an observational study
Sustained transmission of high-level azithromycin-resistant Neisseria gonorrhoeae in England: an observational study
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DOI：
10.1016/s1473-3099(18)30122-1
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发表时间：
2018-05-01
影响因子：
56.3
通讯作者：
Underwood, Apthony
中科院分区：
文献类型：
--
作者：
Fifer, Helen;Cole, Michelle;Underwood, Apthony
背景2014年11月3日至2017年2月24日，英格兰各地报告了70例高度耐阿奇霉素(HL-Azir；最低抑菌浓度[MIC]>；=256 mg/NL)淋球菌。对这次暴发进行了全基因组测序，以确定正在进行的暴发是否代表在利兹发现的一种HL-Azir N淋病菌株的克隆性传播。我们还希望阐明英国淋球菌对阿奇霉素耐药的分子机制。方法对英国分离的HL-Azir淋球菌进行全基因组测序。作为比较，来自英国和爱尔兰的110株阿奇霉素MIC范围的分离株也进行了测序，其中8株来自苏格兰的阿奇霉素MIC在0.12 mg/NL到1.00 mg/NL之间，是淋球菌多抗原序列类型9768(ST9768)，这是最初导致此次暴发的序列类型。在60株来自英国的HL-Azir菌株中，有37株属于ST9768，并且在遗传上相似(平均4.3个单核苷酸多态)。A 2059A。23S rRNA基因的3个或全部4个等位基因均检测到G突变。5个敏感的ST9768菌株有1个突变的23S rRNA等位基因，1个低水平抗性的ST9768菌株有2个突变的等位基因，一个成功的HL-Azir克隆在英格兰被发现持续翻译传播。突变2059A。低阿奇霉素MIC值的菌株中检出G。暴露阿奇霉素可能为23S rRNA基因的一个或两个突变拷贝提供了选择压力，使其与野生型拷贝重组，导致三个或四个突变拷贝和HL-Azir表型。HL-Azir可在低阿奇霉素MIC的分离株中出现，并消除阿奇霉素作为淋病双重治疗的一部分的有效性。
Background Between Nov 3, 2014, and Feb 24, 2017, 70 cases of high-level azithromycin-resistant (HL-AziR; minimum inhibitory concentration [MIC] >= 256 mg/NL) Neisseria gonorrhoeae were reported from across England. Whole-genome sequencing was done to investigate this outbreak to determine whether the ongoing outbreak represented clonal spread of an HL-AziR N gonorrhoeae strain identified in Leeds. We also wanted to elucidate the molecular mechanisms of azithromycin resistance in N gonorrhoeae in the UK.Methods In this observational study, whole-genome sequencing was done on the HL-AziR N gonorrhoeae isolates from England. As comparators, 110 isolates from the UK and Ireland with a range of azithromycin MICs were also sequenced, including eight isolates from Scotland with azithromycin MICs ranging from 0.12 mg/NL to 1.00 mg/NL that were N gonorrhoeae multi-antigen sequence type 9768 ( ST9768), which was the sequence type initially responsible for the outbreak. The presence of mutations or genes associated with azithromycin resistance was also investigated.Findings 37 of the 60 HL-AziR isolates from England belonged to ST9768, and were genetically similar (mean 4.3 single-nucleotide polymorphisms). A 2059A. G mutation was detected in three or all four alleles of the 23S rRNA gene. Five susceptible ST9768 isolates had one mutated 23S rRNA allele and one low-level resistant ST9768 isolate had two mutated alleles.Interpretation Sustained transmission of a successful HL-AziR clone was seen across England. Mutation 2059A. G was found in isolates with lower azithromycin MICs. Azithromycin exposure might have provided the selection pressure for one or two mutated copies of the 23S rRNA gene to recombine with wild-type copies, leading to three or four mutated copies and the HL-AziR phenotype. HL-AziR could emerge in isolates with low azithromycin MICs and eliminate the effectiveness of azithromycin as part of dual therapy for the treatment of gonorrhoea.