Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal.
Laboratory of Microbiology, Biological Sciences Department, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal; CIIMAR/CIMAR-Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Terminal de Cruzeiros do Porto de Leixões, Avenida General Norton de Matos, 4450-208 Matosinhos, Portugal.
Int J Antimicrob Agents. 2020 Jul;56(1):106005. doi: 10.1016/j.ijantimicag.2020.106005. Epub 2020 May 5.
The rise and spread of antimicrobial resistance represents one of the most pressing health issues of today. Antimicrobial resistance in micro-organisms can arise due to a multiplicity of factors, including permeability changes in the cell membrane, increase of drug efflux pumps, enzymatic modification or inactivation of the antibiotic, target site modification, alternative metabolic pathways and biofilm formation. The marine environment is a valuable source of diverse natural products with a huge variety of biological activities. Among them, antimicrobial compounds show promising biological activities against numerous drug-resistant bacteria and fungi, making marine natural products a very promising resource in the search for novel antimicrobial agents. This review summarises the state-of-art of marine natural products with antibacterial and antifungal properties against drug-resistant micro-organisms. These natural products were categorised based on their chemical structure, and their respective sources and activities are highlighted. The chemical diversity associated with these marine-derived molecules is enormous, including peptides, polyketides, alkaloids, sterols, terpenoids, lactones, halogenated compounds, nucleosides, etc., some of which have rare substructures. Some of the marine compounds mentioned do not have intrinsic antimicrobial activity but potentiate the antimicrobial effect of other antimicrobials via inhibition of efflux pumps. Although these agents are still in preclinical studies, evidence of their in vivo efficacy suggest research of new drugs from the ocean to overcome antimicrobial resistance in order to fulfil an unmet medical need.
抗菌药物耐药性的出现和传播是当今最紧迫的健康问题之一。微生物中的抗菌药物耐药性可能由于多种因素引起，包括细胞膜通透性的变化、药物外排泵的增加、抗生素的酶修饰或失活、靶位修饰、替代代谢途径和生物膜形成。海洋环境是具有多种生物活性的各种天然产物的宝贵来源。其中，抗菌化合物对许多耐药菌和真菌表现出有希望的生物活性，使海洋天然产物成为寻找新型抗菌剂的极具前景的资源。本文综述了具有抗耐药微生物的抗菌和抗真菌特性的海洋天然产物的最新研究进展。这些天然产物根据其化学结构进行分类，并强调了它们各自的来源和活性。这些海洋衍生分子具有巨大的化学多样性，包括肽、聚酮、生物碱、甾醇、萜类、内酯、卤代化合物、核苷等，其中一些具有罕见的结构。一些提到的海洋化合物本身没有内在的抗菌活性，但通过抑制外排泵增强其他抗菌药物的抗菌效果。尽管这些药物仍处于临床前研究阶段，但它们在体内疗效的证据表明，有必要从海洋中研究新的药物来克服抗菌药物耐药性，以满足未满足的医疗需求。
