Li Haoran, Maimaitiming Mireguli, Zhou Yue, Li Huaxuan, Wang Pingyuan, Liu Yang, Schäberle Till F, Liu Zhiqing, Wang Chang-Yun
Institute of Evolution & Marine Biodiversity, School of Medicine and Pharmacy, College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China.
Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China.
Mar Drugs. 2022 Mar 4;20(3):192. doi: 10.3390/md20030192.
, one of the most intractable Gram-negative bacteria, has become a public health threat due to its outer polysaccharide layer, efflux transporter system, and high level of biofilm formation, all of which contribute to multi-drug resistance. Even though it is a pathogen of the highest concern, the status of the antibiotic development pipeline is unsatisfactory. In this review, we summarize marine natural products (MNPs) isolated from marine plants, animals, and microorganisms which possess unique structures and promising antibiotic activities against . In the last decade, nearly 80 such MNPs, ranging from polyketides to alkaloids, peptides, and terpenoids, have been discovered. Representative compounds exhibited impressive in vitro anti- activities with MIC values in the single-digit nanomolar range and in vivo efficacy in infectious mouse models. For some of the compounds, the preliminary structure-activity-relationship (SAR) and anti-bacterial mechanisms of selected compounds were introduced. Compounds that can disrupt biofilm formation or membrane integrity displayed potent inhibition of multi-resistant clinical isolates and could be considered as lead compounds for future development. Challenges on how to translate hits into useful candidates for clinical development are also proposed and discussed.
作为最顽固的革兰氏阴性菌之一，因其外多糖层、外排转运系统以及高水平的生物膜形成而成为公共卫生威胁，所有这些因素都导致了多重耐药性。尽管它是最受关注的病原体，但抗生素研发管线的现状并不令人满意。在本综述中，我们总结了从海洋植物、动物和微生物中分离出的海洋天然产物（MNPs），这些产物具有独特的结构，并对具有有前景的抗生素活性。在过去十年中，已经发现了近80种这样的MNPs，从聚酮化合物到生物碱、肽和萜类化合物。代表性化合物在体外显示出令人印象深刻的抗活性，其最低抑菌浓度（MIC）值在个位数纳摩尔范围内，并且在感染小鼠模型中具有体内疗效。对于某些化合物，还介绍了初步的构效关系（SAR）和所选化合物的抗菌机制。能够破坏生物膜形成或膜完整性的化合物对多重耐药临床分离株显示出强大的抑制作用，可以被视为未来开发的先导化合物。还提出并讨论了如何将筛选出的化合物转化为临床开发有用候选物的挑战。
