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临床产碳青霉烯酶分离株中β-内酰胺酶基因的分布及其遗传背景

Distribution of β-Lactamase Genes and Genetic Context of in Clinical Carbapenemase-Producing Isolates.

作者信息

Liu Hongmao, Lin Hailong, Sun Zhewei, Zhu Xinyi, Zhang Xueya, Li Qiaoling, Lu Junwan, Lin Xi, Lin Li, Li Kewei, Zhu Mei, Bao Qiyu, Xu Teng, Hu Yunliang, Zhang Hailin

机构信息

The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou 325027, People's Republic of China.

Key Laboratory of Medical Genetics of Zhejiang Province, Key Laboratory of Laboratory Medicine, Ministry of Education, China, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, People's Republic of China.

出版信息

Infect Drug Resist. 2021 Jan 26;14:237-247. doi: 10.2147/IDR.S290434. eCollection 2021.

Abstract

BACKGROUND

This study was designed to characterize the dissemination mechanism and genetic context of carbapenemase (KPC) genes in carbapenem-resistant (CRKP) isolates.

METHODS

A retrospective analysis was performed on CRKP strains isolated from a teaching hospital of Wenzhou Medical University during 2015-2017. Polymerase chain reaction (PCR)-based amplification and whole-genome sequencing (WGS) were used to analyze the genetic context of the gene. Conjugation experiments were performed to evaluate the transferability of -bearing plasmids. Multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were performed to investigate the clonal relatedness of -producing strains.

RESULTS

The gene was identified from 13.61% (40/294) of clinical isolates. Three different sequence types (ST11, ST15 and ST656) and 5 PFGE subtypes (A to E) were classified among them. ST11 was the dominant sequence type (92.50%, 37/40). Plasmid-oriented antibiotic resistance genes, such as extended spectrum-β-lactamases (ESBLs) and other antimicrobial resistance genes, were also found in KPC-positive (KPC-) isolates. Mapping PCR and genomic sequencing revealed that the -bearing sequence regions, which are related to different mobile elements, including Tn1721- and IS26-based transposons, were mainly located in but not restricted to IncFII-like plasmids and were structurally divergent.

CONCLUSION

The genes related to divergent mobile genetic elements encoded on transferable plasmids may transfer widely, facilitating the spread of carbapenem resistance among bacteria with different genetic backgrounds. The dissemination of -bearing plasmids that collectively carry additional multidrug resistance genes has caused widespread public concern, further limiting the antibiotics available to treat infections caused by KPC-producing pathogens.

摘要

背景

本研究旨在表征耐碳青霉烯类肺炎克雷伯菌(CRKP)分离株中碳青霉烯酶(KPC)基因的传播机制和基因背景。

方法

对2015年至2017年期间从温州医科大学附属某教学医院分离出的CRKP菌株进行回顾性分析。采用基于聚合酶链反应(PCR)的扩增和全基因组测序(WGS)来分析该基因的基因背景。进行接合实验以评估携带KPC的质粒的可转移性。采用多位点序列分型(MLST)和脉冲场凝胶电泳(PFGE)来研究产KPC菌株的克隆相关性。

结果

在294株临床分离株中,13.61%(40/294)鉴定出KPC基因。其中分类出三种不同的序列类型(ST11、ST15和ST656)以及5种PFGE亚型(A至E)。ST11是主要的序列类型(92.50%,37/40)。在KPC阳性(KPC+)分离株中还发现了面向质粒的抗生素耐药基因,如超广谱β-内酰胺酶(ESBLs)和其他抗菌耐药基因。定位PCR和基因组测序显示,与不同移动元件相关的携带KPC的序列区域,包括基于Tn1721和IS26的转座子,主要位于但不限于IncFII样质粒中,并且结构不同。

结论

与可转移质粒上编码的不同移动遗传元件相关的KPC基因可能广泛转移,促进碳青霉烯耐药性在不同遗传背景的细菌之间传播。携带其他多重耐药基因的携带KPC质粒的传播引起了广泛的公众关注,进一步限制了可用于治疗由产KPC病原体引起的感染的抗生素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5675/7847768/5cef73fe8df4/IDR-14-237-g0001.jpg

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