Transposition of insertion sequence element from KPC plasmid enhances intracellular survival of Klebsiella pneumoniae.

IF 10.8 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

EBioMedicine Pub Date : 2025-09-23 DOI:10.1016/j.ebiom.2025.105944

Yingzhou Xie, Zu Cao, Yi-Han Shi, Xiyue Shen, Le-Le Wang, Dong Weng, Jianfeng Zhang, Yiting Wang, Gang Li, Jin-Fu Xu

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引用次数: 0

Abstract

Background: The convergence of plasmids encoding Klebsiella pneumoniae carbapenemase (KPC) and virulence determinants is increasingly reported in K. pneumoniae (Kpn). However, how KPC plasmids interfere with the virulence plasmid-mediated pathogen-host interactions, and the significance of this interference in the within-host adaption of hypervirulent carbapenem-resistant K. pneumoniae (Hv-CR-Kpn), remain unclear.

Methods: An Hv-CR-Kpn variant based on ST11 CR-Kpn was created to determine the impact of capsular polysaccharide (CPS) in Kpn intracellular proliferation. Whole genome sequencing was conducted to find the cause of CPS loss. The biological significance of spontaneous CPS loss in Hv-CR-Kpn was ascertained with cell lines and murine model.

Findings: The acquisition of virulence plasmid resulted in CPS hyperproduction of CR-Kpn, attenuating the bacterial adherence to eukaryotic cells and intracellular proliferation. Spontaneous CPS loss was observed in the Hv-CR-Kpn after phagocytosis by macrophage, as a result from insertion sequence (IS) element transposition from KPC plasmid to chromosomal CPS gene cluster. The loss of capsule hyperproduction enhanced both the in vitro intramacrophage proliferation and evasion of antibiotic killing in vivo of CR-Kpn. The IncF plasmids, the vector for multidrug resistance genes, were characterised as the main reservoir of IS elements in Kpn genomes.

Interpretation: Loss of CPS production enhances the Kpn intracellular proliferation, facilitating evasion of antimicrobial killing. In addition to encoding carbapenemase, IS element transposition acts as an auxiliary mechanism by which the KPC plasmid promotes the adaptive evolution of Hv-CR-Kpn, aiding bacterial survival within the host environment.

Funding: Noncommunicable Chronic Diseases-National Science and Technology Major Project of China, National Natural Science Foundation of China, Key Scientific Innovation Project of Shanghai Municipal Education Commission and Shanghai Sailing Program.

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KPC质粒插入序列元件的转位提高了肺炎克雷伯菌的细胞内存活。

背景：在肺炎克雷伯菌（Kpn）中，编码克雷伯菌碳青霉烯酶（KPC）和毒力决定因素的质粒趋同的报道越来越多。然而，KPC质粒如何干扰毒力质粒介导的病原体-宿主相互作用，以及这种干扰在高毒力耐碳青霉烯肺炎克雷伯菌（Hv-CR-Kpn）宿主内适应中的意义尚不清楚。方法：以ST11 CR-Kpn为基础构建Hv-CR-Kpn变异体，检测荚膜多糖（CPS）对Kpn细胞内增殖的影响。进行全基因组测序，寻找CPS丢失的原因。通过细胞系和小鼠模型确定Hv-CR-Kpn自发性CPS丢失的生物学意义。结果：毒力质粒的获得导致CPS中CR-Kpn的过量产生，减弱细菌对真核细胞的粘附和细胞内增殖。Hv-CR-Kpn被巨噬细胞吞噬后，由于插入序列（IS）元件从KPC质粒转位到染色体CPS基因簇，在Hv-CR-Kpn中观察到自发性CPS丢失。囊膜过度生成的丧失增强了巨噬细胞体外增殖和体内CR-Kpn逃避抗生素杀伤的能力。多药耐药基因载体IncF质粒被认为是Kpn基因组中IS元件的主要储存库。解释：CPS产量的减少增强了Kpn在细胞内的增殖，促进了抗菌素杀伤的逃避。除了编码碳青霉烯酶外，IS元件转位作为KPC质粒促进Hv-CR-Kpn适应性进化的辅助机制，帮助细菌在宿主环境中生存。资助项目：非传染性慢性病国家科技重大专项、国家自然科学基金、上海市教委重点科技创新项目、上海帆船计划。

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

EBioMedicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology

CiteScore

17.70

自引率

0.90%

发文量

579

审稿时长

5 weeks

期刊介绍： eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.