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外膜囊泡介导对碳青霉烯类抗生素耐药的机制。

The mechanism of outer membrane vesicle-mediated resistance to carbapenem antibiotics.

作者信息

Zhou Dan, Yang Xiaoyu, Gao Yuhong, Zheng Rui

机构信息

The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China; Department of Clinical Laboratory, The First People's Hospital of Yunnan Province, Kunming, Yunnan, China; The Affiliated Hospital of College of Medical, Kunming University of Science and Technology, China.

Department of Clinical Laboratory, The First People's Hospital of Yunnan Province, Kunming, Yunnan, China; Regenerative Medicine Research Center, The First People's Hospital of Yunnan Province, Kunming, Yunnan, China; The Affiliated Hospital of College of Medical, Kunming University of Science and Technology, China.

出版信息

Microb Pathog. 2025 Aug;205:107654. doi: 10.1016/j.micpath.2025.107654. Epub 2025 Apr 30.

Abstract

The escalating prevalence of carbapenem resistance in Gram-negative bacteria presents a critical therapeutic challenge, demanding urgent elucidation of novel resistance mechanisms. This review systematically examines the emerging role of outer membrane vesicles (OMVs) as multifunctional mediators of carbapenem resistance, synthesizing recent advances in understanding their biological properties and mechanistic contributions. Through comprehensive analysis of β-lactamase dissemination pathways, we demonstrate that OMVs are extracellular vectors facilitating antibiotic degradation through enzymatic cargo delivery while concurrently acting as genetic transmission vehicles for resistance determinants. Crucially, OMVs exhibit functional versatility in enhancing bacterial survival via dual mechanisms: structurally, by promoting biofilm matrix formation that establishes antibiotic-protected niches, and immunologically, through modulation of host-pathogen interactions that impair microbial clearance. The review further identifies OMV-mediated antibiotic sequestration and competitive binding as underappreciated resistance amplifiers. These insights refine our understanding of resistance evolution and reveal OMV biogenesis pathways as promising therapeutic targets. This synthesis establishes OMVs as central players in carbapenem resistance architecture, providing a strategic framework for developing countermeasures against multidrug-resistant infections.

摘要

革兰氏阴性菌中碳青霉烯耐药性的不断增加带来了严峻的治疗挑战,迫切需要阐明新的耐药机制。本综述系统地研究了外膜囊泡(OMV)作为碳青霉烯耐药性多功能介质的新作用,综合了在理解其生物学特性和机制贡献方面的最新进展。通过对β-内酰胺酶传播途径的全面分析,我们证明OMV是细胞外载体,通过酶货物递送促进抗生素降解,同时作为耐药决定因素的基因传递载体。至关重要的是,OMV通过双重机制在增强细菌存活方面表现出功能多样性:在结构上,通过促进生物膜基质形成来建立抗生素保护的生态位;在免疫方面,通过调节宿主-病原体相互作用来损害微生物清除。该综述进一步确定OMV介导的抗生素螯合和竞争性结合是未被充分认识的耐药增强因素。这些见解完善了我们对耐药性演变的理解,并揭示OMV生物发生途径是有前景的治疗靶点。这一综述确立了OMV是碳青霉烯耐药性结构中的核心参与者,为制定针对多重耐药感染的对策提供了战略框架。

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