Emergence of carbapenem-resistant and colistin-susceptible Enterobacter cloacae complex co-harboring blaIMP-1 and mcr-9 in Japan
Emergence of carbapenem-resistant and colistin-susceptible Enterobacter cloacae complex co-harboring blaIMP-1 and mcr-9 in Japan
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DOI：
10.1186/s12879-020-05021-7
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发表时间：
2020-04-16
影响因子：
3.7
通讯作者：
Kirikae, Teruo
中科院分区：
文献类型：
--
作者：
Kananizadeh, Pegah;Oshiro, Satoshi;Kirikae, Teruo
背景：由质粒介导的粘菌素耐药基因编码的同时产生碳青霉烯酶和MCR的肠杆菌科细菌的传播已经成为一个严重的全球公共卫生问题。本研究描述了三株同时携带BLA(IMP-1)和MCR-9的阴沟肠杆菌临床分离株，它们对碳青霉烯类耐药，但对粘菌素敏感。方法收集日本14家医院临床分离的32株对碳青霉烯类抗生素不敏感的阴沟肠杆菌。用微量肉汤稀释法和E-test法测定其最低抑菌浓度(MIC)。用MiSeq和Minion方法对它们的整个基因组进行了测序。通过对全基因组测序数据进行单核苷酸多态性(SNP)比对，确定多位点序列类型并构建系统发育树。结果32株细菌对亚胺培南和/或美罗培南的最低抑菌浓度(MIC)均为2微克/毫升。全基因组分析表明，所有这些分离株都含有BLA(IMP-1)，其中3株也含有mcr-9。这3株菌对粘菌素的最低抑菌浓度为0.125微克/毫升。在其中两个分离株中，bla(imp-1)和mcr-9分别存在于大小为62kb和280/290kb的两个不同的质粒上。这两个分离株不具有编码双组分系统的qseBC基因，该系统被认为调节mcr-9的表达。然而，在第三个分离株中，bla(IMP-1)和mcr-9都存在于染色体上。结论mcr-9在耐碳青霉烯类阴沟肠杆菌复合分离株中静默分布，在日本医院出现。据我们所知，这是日本首次报道同时含有bla(IMP-1)和mcr-9的阴沟肠杆菌复合体的分离株。
Background The spread of Enterobacteriaceae producing both carbapenemases and Mcr, encoded by plasmid-mediated colistin resistance genes, has become a serious public health problem worldwide. This study describes three clinical isolates of Enterobacter cloacae complex co-harboring bla(IMP-1) and mcr-9 that were resistant to carbapenem but susceptible to colistin. Methods Thirty-two clinical isolates of E. cloacae complex non-susceptible to carbapenems were obtained from patients at 14 hospitals in Japan. Their minimum inhibitory concentrations (MICs) were determined by broth microdilution methods and E-tests. Their entire genomes were sequenced by MiSeq and MinION methods. Multilocus sequence types were determined and a phylogenetic tree constructed by single nucleotide polymorphism (SNP) alignment of whole genome sequencing data. Results All 32 isolates showed MICs of >= 2 mu g/ml for imipenem and/or meropenem. Whole-genome analysis revealed that all these isolates harbored bla(IMP-1), with three also harboring mcr-9. These three isolates showed low MICs of 0.125 mu g/ml for colistin. In two of these isolates, bla(IMP-1) and mcr-9 were present on two separate plasmids, of sizes 62 kb and 280/290 kb, respectively. These two isolates did not possess a qseBC gene encoding a two-component system, which is thought to regulate the expression of mcr-9. In the third isolate, however, both bla(IMP-1) and mcr-9 were present on the chromosome. Conclusion The mcr-9 is silently distributed among carbapenem-resistant E. cloacae complex isolates, of which are emerging in hospitals in Japan. To our knowledge, this is the first report of isolates of E. cloacae complex harboring both bla(IMP-1) and mcr-9 in Japan.