Department of Microbiology and Immunology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
Laboratory for Molecular Biology, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
Front Cell Infect Microbiol. 2024 Mar 6;14:1370062. doi: 10.3389/fcimb.2024.1370062. eCollection 2024.
Antimicrobial resistance is a global threat, leading to an alarming increase in the prevalence of bacterial infections that can no longer be treated with available antibiotics. The World Health Organization estimates that by 2050 up to 10 million deaths per year could be associated with antimicrobial resistance, which would equal the annual number of cancer deaths worldwide. To overcome this emerging crisis, novel anti-bacterial compounds are urgently needed. There are two possible approaches in the fight against bacterial infections: a) targeting structures within bacterial cells, similar to existing antibiotics; and/or b) targeting virulence factors rather than bacterial growth. Here, for the first time, we provide a comprehensive overview of the key steps in the evaluation of potential new anti-bacterial and/or anti-virulence compounds. The methods described in this review include: a) methods for the evaluation of novel compounds; b) anti-bacterial assays (MIC, MBC, Time-kill); b) anti-virulence assays (anti-biofilm, anti-quorum sensing, anti-adhesion); and c) evaluation of safety aspects (cytotoxicity assay and Ames test). Overall, we provide a detailed description of the methods that are an essential tool for chemists, computational chemists, microbiologists, and toxicologists in the evaluation of potential novel antimicrobial compounds. These methods are cost-effective and have high predictive value. They are widely used in preclinical studies to identify new molecular candidates, for further investigation in animal and human trials.
抗微生物药物耐药性是一个全球性威胁，导致细菌感染的流行率惊人增加，而现有抗生素已无法对此类感染进行治疗。世界卫生组织估计，到 2050 年，每年可能有多达 1000 万人因抗微生物药物耐药性而死亡，这将等同于全球每年的癌症死亡人数。为了应对这一新兴危机，迫切需要新型抗菌化合物。对抗细菌感染有两种可能的方法：a）针对细菌细胞内的结构，类似于现有的抗生素；和/或 b）针对毒力因子而不是细菌生长。在这里，我们首次全面概述了评估潜在新的抗菌和/或抗毒力化合物的关键步骤。本综述中描述的方法包括：a）评估新型化合物的方法；b）抗菌测定法（MIC、MBC、时间杀伤）；b）抗毒力测定法（抗生物膜、抗群体感应、抗黏附）；和 c）评估安全性方面（细胞毒性测定和 Ames 试验）。总的来说，我们详细描述了这些方法，它们是化学家、计算化学家、微生物学家和毒理学家评估潜在新型抗菌化合物的重要工具。这些方法具有成本效益和高预测价值。它们广泛应用于临床前研究中，以识别新的分子候选物，进一步在动物和人体试验中进行研究。
