病原始动刺激分子集合/分子对:脓毒症病原学研究的新视角及其应用  

Pathogen-initiated stimulatory molecular panel/pairs (PSMPL/PSMPS): a new point viewing the pathogens of sepsis and their applications

作　　者：王宜强 Wang Yiqiang(Wisdom Lake Academy of Pharmacy,Xi′an Jiaotong-Liverpool University,Suzhou 215123,China)

机构地区：[1]西交利物浦大学慧湖药学院,苏州215123

出　　处：《中华微生物学和免疫学杂志》2025年第3期182-189,共8页Chinese Journal of Microbiology and Immunology

摘　　要：脓毒症是病原体感染后引起的系统性急重病程,因涉及多器官功能衰竭而危及生命,也是COVID-19患者死亡的重要机制之一。但目前对常见病原体引起宿主组织器官破坏与引起脓毒症的机制之间异同缺乏系统对比,且多局限于病原相关分子模式(pathogen-associated molecular patterns,PAMPs)与模式识别受体(pattern recognition receptors,PRRs)的互作。COVID-19研究明确提示SARS-CoV-2主要是刺突蛋白结合宿主细胞的血管紧张素转换酶2而启动疾病及最终激活脓毒症的分子通路,而非以PAMPs即病毒RNA刺激宿主PRRs/TLR7为主。结合对其他关于病原体-宿主互作的证据(如绿脓杆菌鞭毛钩蛋白FlgE刺激血管内皮细胞膜表面异位ATP合酶等),本文提出某特定病原体之能够刺激宿主成分发生反应的所有分子构成"病原始动刺激分子集合"(pathogen-initiated stimulatory molecular panel,PSMPL),是该病原体的固有和相对恒定的生物学特征;而PSMPL在宿主中与宿主分子所能形成的所有分子-分子配对,构成该病原体与该宿主的所有互作通路起点即"病原始动刺激分子对"(pathogen-initiated stimulatory molecular pairs,PSMPS);所有分子对作用的整合结果将决定病原体对宿主细胞或组织器官的净作用。PSMPL/PSMPS概念的提出,将有助于更加深入、全面研究病原体与宿主的互作,帮助寻找引起脓毒症的新通路和新机制,并为鉴定治疗脓毒症的新靶点提供参考。Sepsis is a systemic acute and severe condition caused by pathogen infection,which poses a life-threatening risk due to its involvement or accompanying consequence of multiorgan failure.During the COVID-19 pandemic,sepsis was one of the key mechanisms leading to death in COVID-19 patients.Currently,however,there is a lack of systematic comparison regarding the similarities and differences between the mechanisms by which a common pathogen causes host tissue/organ damages and those that lead to sepsis.Most studies have been limited to the interactions between pathogen-associated molecular patterns(PAMPs)and pattern recognition receptors(PRRs).COVID-19-related sepsis clearly indicates that the molecular pathways through which SARS-CoV-2 initiates disease and ultimately causes sepsis are primarily via the binding of its spike proteins to the host cell′s ACE2 receptors,rather than through PAMPs(such as viral RNA)stimulating PRRs/TLR7.Integrating other evidence regarding pathogen-host interactions(e.g.Pseudomonas aeruginosa flagellar hook protein FlgE stimulating ectopic ATP synthase on surface of vascular endothelial cells),this paper proposes that all molecules of a specific pathogen capable of eliciting reactions in host components constitute the"pathogen-initiated stimulatory molecular panel"(PSMPL),which represents the inherent and relatively constant biological characteristics of that pathogen.Furthermore,all molecular-molecular pairings formed by PSMPL within the host constitute the starting points of all interaction pathways between the pathogen and the host,referred to as"pathogen-initiated stimulatory molecular pairs"(PSMPS).The combinational effects of these molecular pair-mediated stimulations determine the net impact of the pathogen on host cells,tissues,or organs.The introduction of the PSMPL and PSMPS concepts will facilitate deeper and more comprehensive studies of pathogen-host interactions,help to identify new pathways and mechanisms leading to sepsis,and promote the discovery of novel therapeutic t

关 键 词：脓毒症 病原学 病原始动刺激分子集合 病原始动刺激分子对 病原体-宿主互作 

分 类 号：R459.7[医药卫生—急诊医学]