Department of Biology and Environmental Science, College of Science, University of the Philippines Cebu, Lahug, Cebu City, 6000, Philippines.
Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (MOE), Hubei Province Engineering and Technology Research Centre for Fluorinated Pharmaceuticals, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China.
Nat Prod Rep. 2021 Apr 28;38(4):782-821. doi: 10.1039/d0np00061b.
Covering: up to the second quarter of 2020 Threat or treat? While pathogenic bacteria pose significant threats, they also represent a huge reservoir of potential pharmaceuticals to treat various diseases. The alarming antimicrobial resistance crisis and the dwindling clinical pipeline urgently call for the discovery and development of new antibiotics. Pathogenic bacteria have an enormous potential for natural products drug discovery, yet they remained untapped and understudied. Herein, we review the specialised metabolites isolated from entomopathogenic, phytopathogenic, and human pathogenic bacteria with antibacterial and antifungal activities, highlighting those currently in pre-clinical trials or with potential for drug development. Selected unusual biosynthetic pathways, the key roles they play (where known) in various ecological niches are described. We also provide an overview of the mode of action (molecular target), activity, and minimum inhibitory concentration (MIC) towards bacteria and fungi. The exploitation of pathogenic bacteria as a rich source of antimicrobials, combined with the recent advances in genomics and natural products research methodology, could pave the way for a new golden age of antibiotic discovery. This review should serve as a compendium to communities of medicinal chemists, organic chemists, natural product chemists, biochemists, clinical researchers, and many others interested in the subject.
截至 2020 年第二季度 是威胁还是机遇？虽然病原菌构成了重大威胁，但它们也是治疗各种疾病的潜在药物的巨大宝库。令人震惊的抗菌药物耐药性危机和不断减少的临床药物研发管线迫切需要发现和开发新的抗生素。病原菌具有巨大的天然产物药物发现潜力，但它们仍未被开发和研究。在此，我们综述了具有抗细菌和抗真菌活性的昆虫病原细菌、植物病原细菌和人病原细菌分离得到的特殊代谢产物，重点介绍了那些目前处于临床前试验或具有药物开发潜力的代谢产物。本文还描述了一些不常见的生物合成途径，以及它们在各种生态位中（已知情况下）所扮演的关键角色。我们还概述了针对细菌和真菌的作用模式（分子靶标）、活性和最小抑菌浓度（MIC）。利用病原菌作为抗菌药物的丰富来源，结合基因组学和天然产物研究方法的最新进展，可能为抗生素发现的新时代铺平道路。本文综述应作为药物化学家、有机化学家、天然产物化学家、生化学家、临床研究人员以及其他许多对该领域感兴趣的人的参考书。
