Molecular epidemiological analysis of blaNDM-5-producing Klebsiella pneumoniae ST2407-K25 causing infection outbreaks in pediatric patients based on whole genome sequencing.

IF 4.6 2区 医学 Q1 MICROBIOLOGY Annals of Clinical Microbiology and Antimicrobials Pub Date : 2024-10-09 DOI:10.1186/s12941-024-00747-7
Zhangrui Zeng, Caihong Ye, Jingchen Hao, Miran Tang, Xue Xiao, Chunxia Jian, Jinglan Guo, Yinhuan Ding, Jinbo Liu
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Abstract

Background: Pediatric patients are vulnerable to the threat of carbapenem-resistant Klebsiella pneumoniae (CRKP) due to their limited immunity and few available antibiotics. Especially when these pathogens exhibit hypervirulent phenotypes, they are often associated with poor clinical outcomes.

Methods: In this study, we investigated a CRKP outbreak in pediatric patients from 2019 to 2021 in a teaching hospital in China based on whole genome sequencing. We sequenced twenty-nine CRKP isolates isolated from unduplicated pediatric patients to understand their genetic relationships, virulence factors, resistance mechanisms, and transmission trajectories. Conjugation experiments were performed to evaluate the horizontal transfer ability of carbapenem resistance determinants in twenty-nine CRKP isolates. We then characterized these isolates for biofilm formation ability and serum resistance. Genetic relatedness, comparison of plasmids, and chromosomal locus variation of CRKP isolates were analyzed by bioinformatics.

Results: All the isolates were carbapenemase-producers harbouring blaNDM-5. Among them, twenty-eight isolates belonged to the ST2407 group, with the consistent capsular serotype K25. The virulence-related factors: ureA, fim, ybtA, irp1/irp2, and mrkA were prevalent in these isolates. Additionally, most CRKP isolates showed moderately adherent biofilm formation. Although the ST2407 clonal group did not exhibit serum resistance, the heterogeneous level of serum resistance was related to the disruption of oqxR. Conjugation and WGS revealed that the blaNDM-5 carried by the twenty-eight CRKP ST2407 isolates was located on nonconjugative IncX3 plasmids associated with deleting the T4SS-encoding genes. Clonal transmission of CRKP ST2407 in pediatric patients was suggested by the phylogenetic tree.

Conclusions: Our study provides evidence of the clonal spread of blaNDM-5-producing K. pneumoniae in pediatric patients and the necessity for the T4SS system for horizontal transfer of the IncX3 plasmid carrying blaNDM-5. Additionally, the disruption of oqxR may have affected the serum resistance of CRKP. The results of this study emphasize the importance of continuously monitoring for CRKP infection in pediatric patients to prevent recurrent infections.

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基于全基因组测序对导致儿科患者感染爆发的产 blaNDM-5 肺炎克雷伯菌 ST2407-K25 进行分子流行病学分析。
背景:由于免疫力有限且可用抗生素较少,儿科患者很容易受到耐碳青霉烯类肺炎克雷伯菌(CRKP)的威胁。特别是当这些病原体表现出高病毒表型时,往往会导致不良的临床结果:在本研究中,我们基于全基因组测序对中国一家教学医院在 2019 年至 2021 年期间爆发的儿科 CRKP 疫情进行了调查。我们对从无重复的儿科患者中分离出的 29 株 CRKP 进行了测序,以了解它们的遗传关系、毒力因子、耐药机制和传播轨迹。我们进行了共轭实验,以评估 29 个 CRKP 分离物中碳青霉烯类耐药基因的水平转移能力。然后,我们对这些分离株的生物膜形成能力和血清抗性进行了鉴定。通过生物信息学分析了 CRKP 分离物的遗传亲缘关系、质粒比较和染色体位点变异:结果:所有分离株都是碳青霉烯酶生产者,携带 blaNDM-5。其中,28 个分离株属于 ST2407 组,具有一致的胶囊血清型 K25。这些分离物中普遍存在与毒力相关的因子:ureA、fim、ybtA、irp1/irp2 和 mrkA。此外,大多数 CRKP 分离物显示出中度粘附性生物膜形成。虽然 ST2407 克隆组没有表现出血清抗性,但血清抗性的异质性水平与 oqxR 的破坏有关。共轭和 WGS 发现,28 个 CRKP ST2407 分离物携带的 blaNDM-5 位于与删除 T4SS 编码基因相关的非共轭 IncX3 质粒上。系统发生树表明,CRKP ST2407在儿科患者中存在克隆传播:我们的研究提供了产blaNDM-5肺炎克氏菌在儿科患者中克隆传播的证据,并证明了携带blaNDM-5的IncX3质粒的水平转移需要T4SS系统。此外,ocxR的破坏可能影响了CRKP的血清抗性。本研究结果强调了持续监测儿科患者CRKP感染以预防反复感染的重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
8.60
自引率
0.00%
发文量
49
审稿时长
>12 weeks
期刊介绍: Annals of Clinical Microbiology and Antimicrobials considers good quality, novel and international research of more than regional relevance. Research must include epidemiological and/or clinical information about isolates, and the journal covers the clinical microbiology of bacteria, viruses and fungi, as well as antimicrobial treatment of infectious diseases. Annals of Clinical Microbiology and Antimicrobials is an open access, peer-reviewed journal focusing on information concerning clinical microbiology, infectious diseases and antimicrobials. The management of infectious disease is dependent on correct diagnosis and appropriate antimicrobial treatment, and with this in mind, the journal aims to improve the communication between laboratory and clinical science in the field of clinical microbiology and antimicrobial treatment. Furthermore, the journal has no restrictions on space or access; this ensures that the journal can reach the widest possible audience.
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