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解读肺炎克雷伯菌的毒力与耐药性:药理学见解、免疫动力学及计算机模拟治疗策略

Decoding virulence and resistance in Klebsiella pneumoniae: Pharmacological insights, immunological dynamics, and in silico therapeutic strategies.

作者信息

Alishvandi Ali, Barancheshemeh Maryam, Firuzpour Faezeh, Aram Cena, Kamali Mohammad Javad, Keikha Masoud

机构信息

Student Research Committee, Iranshahr University of Medical Sciences, Iranshahr, Iran; Department of Immunology, School of Medicine, Iranshahr University of Medical Sciences, Iranshahr, Iran.

Universal Scientific Education and Research Network (USERN), Reno, USA.

出版信息

Microb Pathog. 2025 Aug;205:107691. doi: 10.1016/j.micpath.2025.107691. Epub 2025 May 10.

DOI:10.1016/j.micpath.2025.107691
PMID:40355055
Abstract

Klebsiella pneumoniae (K. pneumoniae) has become a serious global health concern due to its rising virulence and antibiotic resistance. As one of the leading members of ESKAPE pathogens, it plays a major role in a wide range of infections that cause pneumonia, urinary tract infections, and bacteremia, especially in immunocompromised and hospitalized patients. The recent increase in multidrug-resistant (MDR) and hypervirulent (hvKP) strains due to the production of extended-spectrum beta-lactamases (ESBLs) and carbapenemases, has greatly limited therapeutic options that highlights the need for novel approaches to combat the pathogen. This review outlines the virulence mechanisms, profiles of antibiotic resistance, and immune evasion strategies in K. pneumoniae. Also, it points out the role of capsular polysaccharides, lipopolysaccharides, and fimbriae in host colonization and immune evasion. Additionally, the review discusses the emerging therapeutic strategies of vaccine development, computational drug discovery, and the use of artificial intelligence (AI). The progress achieved in reverse vaccinology and structural biology enables the identification of new drug and vaccine targets, whereas AI and machine learning (ML) stand out as powerful candidates for high-throughput screening and drug design. However, challenges with antigenic variability, safety, and the need to collaborate globally still exist. This review focuses on the need for interdisciplinary approaches involving molecular biology and immunology with computational sciences to address K. pneumoniae infections and provide appropriate therapies in the era of antibiotic resistance.

摘要

肺炎克雷伯菌因其不断增强的毒力和抗生素耐药性,已成为全球严重的公共卫生问题。作为ESKAPE病原体的主要成员之一,它在引起肺炎、尿路感染和菌血症等多种感染中起主要作用,尤其是在免疫功能低下和住院患者中。由于超广谱β-内酰胺酶(ESBLs)和碳青霉烯酶的产生,近期多重耐药(MDR)和高毒力(hvKP)菌株的增加,极大地限制了治疗选择,凸显了对抗该病原体新方法的必要性。本综述概述了肺炎克雷伯菌的毒力机制、抗生素耐药谱和免疫逃逸策略。此外,还指出了荚膜多糖、脂多糖和菌毛在宿主定植和免疫逃逸中的作用。另外,本综述讨论了疫苗开发、计算机辅助药物发现和人工智能(AI)应用等新兴治疗策略。反向疫苗学和结构生物学取得的进展能够确定新的药物和疫苗靶点,而人工智能和机器学习(ML)在高通量筛选和药物设计方面表现突出。然而,抗原变异性、安全性以及全球合作需求等挑战依然存在。本综述着重强调了在抗生素耐药时代,需要采用涉及分子生物学、免疫学和计算科学的跨学科方法来应对肺炎克雷伯菌感染并提供适当治疗。

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