Yoon Eun-Jeong, Gwon Bareum, Liu Changseung, Kim Dokyun, Won Dongju, Park Sung Gyun, Choi Jong Rak, Jeong Seok Hoon
Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, South Korea.
Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, South Korea.
mSystems. 2020 Sep 29;5(5):e00459-20. doi: 10.1128/mSystems.00459-20.
The acquired CTX-M-type extended-spectrum-β-lactamase (ESBL)-producing are of great concern in clinical settings because they limit therapeutic options for patients infected by the pathogens. An intriguing clonality of CTX-M ESBL-producing blood isolates was observed from a national cohort study, and comparative genomics were assessed for the 115 blood isolates carrying the gene. The plasmid preference of particular clones of a sequence type (ST) was assessed by liquid mating. A quarter of the gene-carrying blood isolates harbor the gene in their chromosome, and most of those with the built-in gene belonged either to ST307 or ST48. Notably, all 16 ST48 isolates harbored two copies of the gene in the chromosome. The chromosomal integration of the gene was mostly derived from the IS-targeting 5-bp AT-rich locus in the chromosome. The IS-mediated chromosomal integration occurred when the upstream IS from the gene was truncated, targeting the anchor IS copy in the chromosome. Higher transfer efficiency of the gene-carrying FIA:R plasmid was observed in ST17 than that of the gene-carrying FIB:FII plasmid. The transfer efficiency of the plasmid differed by isolate among the ST307 members. The clones ST307 and ST48 harboring the gene in the chromosome were able to disseminate stably in clinical settings regardless of the environmental pressure, and the current population of blood isolates was constructed. Further follow-up is needed for the epidemiology of this antimicrobial resistance. Dominant F-type plasmids harboring the gene have been pointed out to be responsible for the dissemination of the CTX-M extended-spectrum-β-lactamase (ESBL)-producing Recently, the emergence of isolates with the gene in their chromosomes has been reported occasionally worldwide. Such a chromosomal location of the resistance gene could be beneficial for stable propagation, as was the ST191 harboring chromosomal that is endemic to South Korea. Through the present study, particular clones were identified as having built-in resistance genes in their chromosomes, and the chromosomal integration events were tracked by assessing their genomes. The cefotaxime-resistant clones of this study were particularized as results of the fastidiousness for plasmids to acquire the gene for securing the diversity and of the chromosomal addiction of the gene for ensuring propagation.
获得性产CTX-M型超广谱β-内酰胺酶（ESBL）的细菌在临床环境中备受关注，因为它们限制了感染这些病原体患者的治疗选择。一项全国队列研究观察到产CTX-M ESBL的血液分离株存在有趣的克隆性，并对携带该基因的115株血液分离株进行了比较基因组学评估。通过液体交配评估特定序列类型（ST）克隆的质粒偏好性。四分之一携带该基因的血液分离株在其染色体中含有该基因，并且大多数内置该基因的分离株属于ST307或ST48。值得注意的是，所有16株ST48分离株在染色体中都含有两个该基因拷贝。该基因的染色体整合主要源于染色体中富含AT的5bp IS靶向位点。当该基因上游的IS被截断并靶向染色体中的锚定IS拷贝时，就会发生IS介导的染色体整合。在ST17中观察到携带FIA:R质粒的该基因转移效率高于携带FIB:FII质粒的该基因。ST307成员中质粒的转移效率因分离株而异。在染色体中携带该基因的ST307和ST48克隆能够在临床环境中稳定传播，而不受环境压力影响，并且构建了当前的血液分离株群体。这种抗菌药物耐药性的流行病学还需要进一步随访。携带该基因的优势F型质粒已被指出是产CTX-M超广谱β-内酰胺酶（ESBL）细菌传播的原因。最近，世界各地偶尔报道了染色体中含有该基因的分离株的出现。这种耐药基因的染色体定位可能有利于稳定传播，就像韩国特有的携带染色体blaCTX-M-15的ST191一样。通过本研究，确定了特定克隆在其染色体中具有内置耐药基因，并通过评估其基因组追踪染色体整合事件。本研究中对头孢噻肟耐药的克隆是由于质粒获取该基因以确保多样性的挑剔性以及该基因的染色体成瘾性以确保传播的结果。
