Resistance genes and plasmids of a multi-drug resistant Shigella sonnei strain carrying both blaCTX-M-14 and blaCTX-M-15 genes
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摘要:
目的 对1株同时耐头孢菌素和阿奇霉素的多重耐药宋内志贺菌进行全基因组测序分析,明确其携带的耐药基因和质粒特征。 方法 通过对2011年上海市的60株宋内志贺菌进行抗菌药物敏感性分析,筛选出1株同时耐头孢菌素和阿奇霉素的菌株Sh11sh529,使用二代和纳米孔测序技术获得其基因组序列,分析基因组的耐药基因、质粒、可移动遗传元件等。 结果 Sh11sh529基因组中检测到了11个耐药基因以及gyrA基因喹诺酮耐药决定区(QRDR)的突变位点gyrA-S83L,耐药基因包括2种CTX-M型超广谱β内酰胺酶(ESBL)基因blaCTX-M-14和blaCTX-M-15,其中blaCTX-M-14、mphA、aac(3)-IId、dfrA17、aadA5、sul1和qacEdelta基因由1个IncB/O/K/Z型质粒pSh11sh529-2携带,blaCTX-M-14上游有1个ISEcp1插入子,mphA上游有1个IS26插入子。 而blaCTX-M-15由IncFII型质粒pSh11sh529-3携带,在其上游有1个ISEcp1插入子。 该菌株表现出多重耐药性,对头孢菌素类、大环内酯类、氨基糖苷类、磺胺类、青霉素类等5类抗菌药物中的9种耐药。 结论 应当加强对多重耐药菌株以及同时携带多个类型ESBL菌株的监测和研究,以制定策略减少其流行和传播。 Abstract:Objective To analyze the whole genome sequencing of a multi-drug resistant Shigella sonnei strain resistant to both cephalosporin and azithromycin and identify the characteristics of its resistance genes and plasmids. Methods A cephalosporin and azithromycin resistant S. sonnei strain (Sh11sh529) was screened by analyzing the antibiotic susceptibility of 60 S. sonnei strains collected from Shanghai in 2011, and genome sequence of the strain was obtained by second-generation sequencing and nanopore sequencing technology. The drug resistance genes, plasmids and genetic mobile elements were analyzed. Results Eleven resistance genes and gyrA-S83L mutation sites in quinolone resistance determining region (QRDR) of gyrA gene were detected in genome of the Sh11sh529 strain. The resistance genes included two extended spectrum β-lactamases (ESBLs) genes blaCTX-M-14 and blaCTX-M-15. The blaCTX-M-14, mphA, aac(3)-IId, dfrA17, aadA5, sul1 and qacEdelta genes were carried by an IncB/O/K/Z plasmid (pSh11sh529-2). There was an ISEcp1 insert in upstream of blaCTX-M-14, an IS26 insert in upstream of mphA. The blaCTX-M-15 gene was carried by an IncFII plasmid (pSh11sh529-3), and there was an ISEcp1 insert in upstream of blaCTX-M-15. The strain was resistant to 9 antibiotics of 5 classes, including cephalosporins, macrolides, aminoglycosides, sulfonamides, and penicillins. Conclusion It is necessary to strengthen the surveillance and research of multi-drug resistant strains and strains carrying multiple types of ESBL for the development of strategies to reduce the prevalence and spread of multi-drug resistant strains. -
表 1 Sh11sh529的药物敏感性
Table 1. Drug susceptibility of strain Sh11sh529
抗菌药物种类 抗菌药物 MIC
(μg/mL)药物
敏感性氨基糖苷类 妥布霉素 ≥16 耐药 庆大霉素 ≥16 耐药 阿米卡星 ≤16 敏感 碳青霉烯类 亚胺培南 ≤4 敏感 头孢菌素类 头孢曲松 ≥64 耐药 头孢他啶 16 中等 头孢西丁 ≤8 敏感 头孢哌酮 ≥64 耐药 头孢吡肟 ≤8 敏感 头孢唑啉 ≥32 耐药 氟喹诺酮类 诺氟沙星 ≤4 敏感 左氧氟沙星 ≤2 敏感 叶酸通路抑制剂 甲氧苄胺嘧啶/磺胺甲基异恶唑 ≥4/76 耐药 大环内酯类 阿奇霉素 ≥32 耐药 单环β内酰胺类 氨曲南 16 中等 硝基呋喃 呋喃妥因 ≤32 敏感 青霉素类 替卡西林 ≥128 耐药 哌拉西林 ≥128 耐药 氨苄西林 ≥32 耐药 氯霉素类 氯霉素 ≤8 敏感 四环素类 四环素 ≤4 敏感 β-内酰胺类/ β-内酰胺酶抑制剂 替卡西林/克拉维酸 32/264/2 中等 注:MIC. 最小抑菌浓度 表 2 Sh11sh529携带的主要耐药基因
Table 2. Main resistance genes carried by strain Sh11sh529
序列类型 起始位点 终止位点 耐药基因 匹配度(%) 覆盖度(%) 染色体 1 962 708 1 963 496 aadA1 99.36 100.00 染色体 1 963 554 1 964 078 sat-2 100.00 100.00 染色体 1 964 173 1 964 606 dfrA1 99.62 99.62 pSh11sh529-2 110 933 111 808 blaCTX-M-14 100.00 100.00 pSh11sh529-2 54 479 55 078 dfrA17 100.00 100.00 pSh11sh529-2 53 560 54 348 aadA5 100.00 100.00 pSh11sh529-2 53 007 53 354 qacEdelta1 100.00 100.00 pSh11sh529-2 52 174 53 013 sul1 100.00 100.00 pSh11sh529-2 47 555 48 415 aac(3)-IId 100.00 100.00 pSh11sh529-2 43 130 44 035 mphA 100.00 100.00 pSh11sh529-3 61 400 62 275 blaCTX-M-15 100.00 100.00 -
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