PA0328与碳青霉烯耐药铜绿假单胞菌的毒力和免疫逃避有关

IF 3.5 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis Pub Date : 2025-09-11 DOI:10.1016/j.micpath.2025.107920

Yuan He , Yongli Song , Yating Zhang , Lingge Su , Shuang Qin , Chunyan Wu , Guibo Song

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引用次数: 0

摘要

背景铜绿假单胞菌是一种主要的医院病原菌。它在医院环境中的持久性和逃避宿主免疫反应的能力与多种毒力因素密切相关。目的探讨PA0328在耐碳青霉烯类假单胞菌（Pseudomonas aeruginosa， CRPA）关键致病性状中的调控作用，特别是其与宿主免疫细胞的相互作用。方法1例慢性阻塞性肺病患者（BALF样本）广泛耐药的CRPA分离物具有粘菌素耐药和生物膜精通。它是转座子诱变的基础。我们确定PA0328是毒力的关键调节因子。功能分析证实了它在调节花青素生产、生物膜形成、细菌运动和巨噬细胞相互作用中的作用。通过基因表达分析探索其调控靶点，特别是群体感应相关通路。结果spa0328是多个毒力过程的关键调控因子。它调节花青素合成、生物膜动力学和运动性。值得注意的是，PA0328通过平衡细菌粘附和对吞噬的抵抗来微调巨噬细胞的相互作用，这对于CRPA在宿主中的存活和传播至关重要。从机制上讲，PA0328抑制群体感应相关基因，揭示了控制CRPA毒力的调控轴。结论pa0328通过调控多种毒力相关过程和巨噬细胞反应，在调控CRPA致病性中发挥核心作用。它代表了针对CRPA感染的抗毒治疗的一个有希望的靶点。

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PA0328 is associated with virulence and immune evasion in carbapenem-resistant Pseudomonas aeruginosa

Background

Pseudomonas aeruginosa is a major nosocomial pathogen. Its persistence in hospital environments and ability to evade host immune responses are closely linked to multiple virulence factors.

Objective

This study aimed to investigate the regulatory role of PA0328 in controlling key pathogenic traits of carbapenem-resistant Pseudomonas aeruginosa (CRPA), particularly its interactions with host immune cells.

Methods

An extensively drug-resistant CRPA isolate from a COPD patient (BALF sample) was colistin-resistant and biofilm-proficient. It served as the basis for transposon mutagenesis. We identified PA0328 as a critical regulator of virulence. Functional assays confirmed its role in modulating pyocyanin production, biofilm formation, bacterial motility, and macrophage interaction. The gene expression analysis were used to explore its regulatory targets, especially quorum sensing-associated pathways.

Results

PA0328 was identified as a pivotal regulator of multiple virulence processes. It modulates pyocyanin synthesis, biofilm dynamics, and motility. Notably, PA0328 fine-tunes macrophage interactions by balancing bacterial adhesion and resistance to phagocytosis, which was essential for CRPA survival and dissemination in the host. Mechanistically, PA0328 repressed quorum sensing-related genes, unveiling a regulatory axis controlling CRPA virulence.

Conclusion

PA0328 plays a central role in orchestrating CRPA pathogenicity by regulating multiple virulence-related processes and macrophage responses. It represents a promising target for anti-virulence therapies against CRPA infections.

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来源期刊

Microbial pathogenesis 医学-免疫学

CiteScore

7.40

自引率

2.60%

发文量

472

审稿时长

56 days

期刊介绍： Microbial Pathogenesis publishes original contributions and reviews about the molecular and cellular mechanisms of infectious diseases. It covers microbiology, host-pathogen interaction and immunology related to infectious agents, including bacteria, fungi, viruses and protozoa. It also accepts papers in the field of clinical microbiology, with the exception of case reports. Research Areas Include: -Pathogenesis -Virulence factors -Host susceptibility or resistance -Immune mechanisms -Identification, cloning and sequencing of relevant genes -Genetic studies -Viruses, prokaryotic organisms and protozoa -Microbiota -Systems biology related to infectious diseases -Targets for vaccine design (pre-clinical studies)