关键词: Caribbean ESBL Enterobacter cloacae complex Nanopore ST114 ST1503 healthcare hsp60 molecular sequencing plasmid

来  源:   DOI:10.3390/antibiotics11101443   PDF(Pubmed)

Abstract:
Between April 2018 and August 2019, a total of 135 strains of Enterobacter cloacae complex (ECC) were randomly collected at the University Hospital Center of Guadeloupe to investigate the structure and diversity of the local bacterial population. These nosocomial isolates were initially identified genetically by the hsp60 typing method, which revealed the clinical relevance of E. xiangfangensis (n = 69). Overall, 57/94 of the third cephalosporin-resistant strains were characterized as extended-spectrum-β-lactamase (ESBL) producers, and their whole-genome was sequenced using Illumina technology to determine the clonal relatedness and diffusion of resistance genes. We found limited genetic diversity among sequence types (STs). ST114 (n = 13), ST1503 (n = 9), ST53 (n = 5) and ST113 (n = 4), which belong to three different Enterobacter species, were the most prevalent among the 57 ESBL producers. The blaCTXM-15 gene was the most prevalent ESBL determinant (56/57) and was in most cases associated with IncHI2/ST1 plasmid replicon carriage (36/57). To fully characterize this predominant blaCTXM-15/IncHI2/ST1 plasmid, four isolates from different lineages were also sequenced using Oxford Nanopore sequencing technology to generate long-reads. Hybrid sequence analyses confirmed the circulation of a well-conserved plasmid among ECC members. In addition, the novel ST1503 and its associated species (ECC taxon 4) were analyzed, in view of its high prevalence in nosocomial infections. These genetic observations confirmed the overall incidence of nosocomial ESBL Enterobacteriaceae infections acquired in this hospital during the study period, which was clearly higher in Guadeloupe (1.59/1000 hospitalization days) than in mainland France (0.52/1,000 hospitalization days). This project revealed issues and future challenges for the management and surveillance of nosocomial and multidrug-resistant Enterobacter in the Caribbean.
摘要:
在2018年4月至2019年8月之间,在瓜德罗普岛大学医院中心随机收集了135株阴沟肠杆菌(ECC),以调查当地细菌种群的结构和多样性。这些医院分离株最初是通过hsp60分型方法进行遗传鉴定的,这揭示了香方大肠杆菌(n=69)的临床相关性。总的来说,57/94的第三个头孢菌素耐药菌株被表征为超广谱β-内酰胺酶(ESBL)生产者,使用Illumina技术对它们的全基因组进行测序,以确定抗性基因的克隆相关性和扩散。我们发现序列类型(STs)之间的遗传多样性有限。ST114(n=13),ST1503(n=9),ST53(n=5)和ST113(n=4),属于三种不同的肠杆菌,在57个ESBL生产商中最普遍。blaCTXM-15基因是最普遍的ESBL决定子(56/57),并且在大多数情况下与IncHI2/ST1质粒复制子携带(36/57)相关。为了充分表征这种主要的blaCTXM-15/IncHI2/ST1质粒,还使用牛津纳米孔测序技术对来自不同谱系的四种分离物进行了测序,以产生长读段。杂交序列分析证实了ECC成员中保存良好的质粒的循环。此外,对新型ST1503及其相关物种(ECC分类群4)进行了分析,鉴于其在医院感染中的高患病率。这些遗传观察证实了在研究期间在该医院获得的院内ESBL肠杆菌科感染的总体发生率,瓜德罗普岛(1.59/1000住院天数)明显高于法国大陆(0.52/1000住院天数)。该项目揭示了加勒比地区医院和多重耐药肠杆菌管理和监测的问题和未来挑战。
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