细菌内抗菌药物积累测定方法研究进展

doi:10.16431/j.cnki.1671-7236.2025.01.041

摘要/Abstract

摘要： 抗菌药是治疗细菌感染的关键药物,也是现代医学中至关重要的基础药物之一。但当前现有抗菌药物耐药性日益严重以及新抗菌药物发现渠道不足的问题已受到关注并亟需解决。抗菌药透过细菌的外膜屏障且在作用靶点位置蓄积至有效浓度才能发挥抗菌作用。因此,测定细菌内抗菌药物的含量,有助于建立药物在细菌内蓄积特性与其结构之间的关系,为新型抗菌药物设计提供指导。目前,已有多种检测方法被开发用于细菌内抗菌药物浓度测定。笔者首先简要介绍了革兰阳性菌和革兰阴性菌细胞膜的结构差异,再从早期的放射性测定法、荧光测定法及基于质谱开发的新型方法(包括液相色谱串联质谱检测法、固相萃取-质谱测定法、纳米流体-质谱联用技术、飞行时间二次离子质谱和生物探针与质谱的联合应用)入手,介绍各检测方法及当前的应用,并总结概述了上述方法的优缺点,对其今后的发展进行了展望,以期为后续细菌内抗菌药物积累测定方法的应用提供建议,为设计和发现新的抗菌药物尤其是抗革兰阴性菌新药提供参考。

关键词: 抗菌药物; 抗菌药物摄取; 检测方法; 细胞内积累; 亚细胞定位

Abstract: Antibacterial agents are the key drugs for the treatment of bacterial infections and one of the most important foundation drugs in modern medicine.However,the current problems of increasingly serious antimicrobial resistance and insufficient channels for new antimicrobial agent discovery have attracted attention and need to be solved urgently.Antibacterial activity is acted when antibacterial agents permeate across the bacterial outer membrane and accumulate to effective concentration at the target.Therefore,measuring the cellular accumulation of antibacterial agents in bacteria would be helpful to establish the relationships between properties of the intracellular accumulation of compounds and their structures.The guidance for the design of new antibacterial agents could be provided through these relationships.At present,a variety of detection methods have been developed for the determination of antimicrobial agent concentration in bacteria.This paper briefly introduced the structural differences of cell membranes between Gram-positive bacteria and Gram-negative bacteria.Subsequently,radiometric assay,fluorometric assay and new methods based on mass spectrometry,which included LC-MS/MS,SPE-MS,nanofluidics-MS,TOF-SIMS and biological probes were reviewed.Each detection method and their current applications were presented.The advantages and disadvantages of the above analysis methods were summarized,and prospects were made for future development,with the aim of providing suggestions for the application of the assays of antimicrobial agent accumulation in bacteria,and reference for the design and development of new antibacterial agents,especially new drugs against Gram-negative bacteria.

Key words: antimicrobial agents; antimicrobial uptake; detection methods; intracellular accumulation; subcellular localization

中图分类号:

S859.7

孙丽, 谭冰冰, 李长琼, 袁欣怡, 潘源虎. 细菌内抗菌药物积累测定方法研究进展[J]. 中国畜牧兽医, 2025, 52(1): 451-460.

SUN Li, TAN Bingbing, LI Changqiong, YUAN Xinyi, PAN Yuanhu. Research Progress on the Methods for Determination of Antimicrobial Agents Accumulation in Bacteria[J]. China Animal Husbandry and Veterinary Medicine, 2025, 52(1): 451-460.

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