肺炎克雷伯菌中由新型 IncN 样质粒介导的毒力质粒的共轭传播

IF 6.1 1区 生物学 Q1 MICROBIOLOGY Microbiological research Pub Date : 2024-09-05 DOI:10.1016/j.micres.2024.127896
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引用次数: 0

摘要

肺炎克雷伯菌(Kp)越来越被认为是一系列抗生素耐药基因的贮藏库,也是一种在医院和社区环境中经常引起严重感染的病原体。在这项研究中,我们发现了一种非共轭型毒力质粒的新型共轭转移机制,即毒力质粒与 59,162 bp 的新型 IncN- 质粒之间形成融合质粒。研究发现,这种质粒是一种具有多重耐药性(MDR)的质粒,并携带一个 T4SS 簇,这极大地促进了融合质粒在 Kp 菌株之间的高效水平转移。融合后的毒力质粒使转染株具有抗血清杀灭和巨噬细胞吞噬的能力。重要的是,在小鼠模型中,该质粒被证明对 Kp 的毒力至关重要。机理分析表明,该毒力质粒编码的毒力因子有助于抵抗体内清除,并诱导高水平的促炎细胞因子IL-1β,从而诱导更多的中性粒细胞募集。Kp中融合质粒的传播有可能使其转化为MDR和高病毒性Kp,加速其进化,对人类健康构成严重威胁。本研究的发现为近年来 MDR 和高病毒性 Kp 的快速进化提供了新的视角。
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Conjugative transmission of virulence plasmid in Klebsiella pneumoniae mediated by a novel IncN-like plasmid

Klebsiella pneumoniae (Kp) is increasingly recognized as a reservoir for a range of antibiotic resistance genes and a pathogen that frequently causes severe infections in both hospital and community settings. In this study, we have identified a novel mechanism of conjugative transfer of a non-conjugative virulence plasmid through the formation of a fusion plasmid between the virulence plasmid and a novel 59,162 bp IncN- plasmid. This plasmid was found to be a multidrug-resistance (MDR) plasmid and carried a T4SS cluster, which greatly facilitated the efficient horizontal transfer of the fusion plasmid between Kp strains. The fused virulence plasmid conferred the resistance of serum killing and macrophage phagocytosis to the transconjugants. Importantly, this plasmid was shown to be essential for Kp virulence in a mouse model. Mechanistic analysis revealed that the virulence factors encoded by this virulence plasmid contributed to resistance to in vivo clearance and induced a high level of proinflammatory cytokine IL-1β, which acts as an inducer for more neutrophil recruitment. The transmission of the fusion plasmid in Kp has the potential to convert it into both MDR and hypervirulent Kp, accelerating its evolution, and posing a serious threat to human health. The findings of this study provide new insights into the rapid evolution of MDR and hypervirulent Kp in recent years.

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来源期刊
Microbiological research
Microbiological research 生物-微生物学
CiteScore
10.90
自引率
6.00%
发文量
249
审稿时长
29 days
期刊介绍: Microbiological Research is devoted to publishing reports on prokaryotic and eukaryotic microorganisms such as yeasts, fungi, bacteria, archaea, and protozoa. Research on interactions between pathogenic microorganisms and their environment or hosts are also covered.
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