The substrate-binding protein DppA modulates the virulence of hypervirulent Klebsiella pneumoniae

IF 3.6 3区医学 Q1 MICROBIOLOGY

International Journal of Medical Microbiology Pub Date : 2026-06-01 Epub Date: 2025-12-17 DOI:10.1016/j.ijmm.2025.151697

Rongping Zhu , Qingzhu Zheng , Jiacheng Qiu , Yingping Cao , Xiaohong Xu

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引用次数: 0

Abstract

Hypervirulent Klebsiella pneumoniae (hvKp), one of the most significant pathogens in nosocomial infections, regulates the shift from long-term survival to pathogenicity via an intricate regulatory network. Nevertheless, the mechanism by which hvKp manages to uphold a variety of metabolic shifts occurring in its immediate vicinity could play a significant role in bolstering its virulence. Through the identification of DppA, a crucial component of the dipeptide (Dpp) transporter system, our findings revealed a link between DppA and the regulation of virulence and metabolism in hvKp. Significant phenotypic alterations were observed in the dppA deletion mutant, including increased biofilm formation, improved serum resistance, enhanced siderophores production, improved cell adhesion and infection, and, most crucially, in a mouse model of bloodstream infection, we demonstrated that the dppA deletion markedly increased the expression of the inflammatory mediator IL-6. Furthermore, approximately 2.5 % of the genes exhibited differential expression in the mutant, with virulence-associated genes (particularly those related to siderophores) showing substantially elevated expression levels. This study deciphers the role of DppA within the virulence and metabolic regulatory networks of hvKp, thereby establishing a foundation for future research into its pathogenic mechanisms.

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底物结合蛋白DppA调节高致病性肺炎克雷伯菌的毒力

高致病性肺炎克雷伯菌（hvKp）是院内感染中最重要的病原体之一，它通过一个复杂的调节网络调节从长期存活到致病性的转变。然而，hvKp设法维持其附近发生的各种代谢变化的机制可能在增强其毒力方面发挥重要作用。通过鉴定二肽（Dpp）转运体系统的关键组成部分DppA，我们的研究结果揭示了DppA与hvKp毒力和代谢调节之间的联系。在dppA缺失突变体中观察到显著的表型改变，包括增加生物膜形成，改善血清抵抗，增强铁载体产生，改善细胞粘附和感染，最重要的是，在小鼠血流感染模型中，我们证明dppA缺失显著增加炎症介质IL-6的表达。此外，大约2.5 %的基因在突变体中表现出差异表达，毒力相关基因（特别是与铁载体相关的基因）的表达水平显著升高。本研究揭示了DppA在hvKp毒力和代谢调控网络中的作用，为进一步研究其致病机制奠定了基础。

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

International Journal of Medical Microbiology 医学-病毒学

CiteScore

9.70

自引率

0.00%

发文量

审稿时长

45 days

期刊介绍： Pathogen genome sequencing projects have provided a wealth of data that need to be set in context to pathogenicity and the outcome of infections. In addition, the interplay between a pathogen and its host cell has become increasingly important to understand and interfere with diseases caused by microbial pathogens. IJMM meets these needs by focussing on genome and proteome analyses, studies dealing with the molecular mechanisms of pathogenicity and the evolution of pathogenic agents, the interactions between pathogens and host cells ("cellular microbiology"), and molecular epidemiology. To help the reader keeping up with the rapidly evolving new findings in the field of medical microbiology, IJMM publishes original articles, case studies and topical, state-of-the-art mini-reviews in a well balanced fashion. All articles are strictly peer-reviewed. Important topics are reinforced by 2 special issues per year dedicated to a particular theme. Finally, at irregular intervals, current opinions on recent or future developments in medical microbiology are presented in an editorial section.