外排泵抑制剂苯丙氨酸-精氨酸-β-萘甲酰胺类似物增强了 5-O-mycaminosyltylonolide 对多重耐药铜绿假单胞菌的活性。

IF 2.1 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Journal of Antibiotics Pub Date : 2024-03-11 DOI:10.1038/s41429-024-00713-7

Aoi Kimishima, Masako Honsho, Junsei Terai, Paul Wasuwanich, Sota Honma, Hidehito Matsui, Hideaki Hanaki, Yukihiro Asami

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引用次数: 0

摘要

抗生素耐药性的出现和传播是全球性威胁。铜绿假单胞菌（P. aeruginosa）是造成这一全球健康问题的主要原因，因为它的外膜和多药外排泵系统具有抗渗透性，因而对许多抗生素具有固有的耐药性。因此，治疗药物有限，新药开发极具挑战性。作为一种替代方法，我们将重点放在了联合治疗策略上，并发现 5-O-mycaminosyltylonolide（OMT）在外排泵抑制剂苯丙氨酸-精氨酸-β-萘甲酰胺（PAβN）的作用下对铜绿假单胞菌显示出了强大的抗菌活性。在本报告中，我们制备了一种 PAβN 衍生物，并比较了 PAβNs 对多重耐药铜绿假单胞菌临床分离株的 OMT 增效活性。

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Efflux pump inhibitor, phenylalanine-arginine beta-naphthylamide analog potentiates the activity of 5-O-mycaminosyltylonolide for multi-drug resistant Pseudomonas aeruginosa

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Efflux pump inhibitor, phenylalanine-arginine beta-naphthylamide analog potentiates the activity of 5-O-mycaminosyltylonolide for multi-drug resistant Pseudomonas aeruginosa

The emergence and spread of antimicrobial resistance are global threats. Pseudomonas aeruginosa (P. aeruginosa) is responsible for a substantial proportion of this global health issue because of its intrinsic resistance to many antibiotics due to the impermeability of its outer membrane and its multidrug efflux pump systems. Therefore, therapeutic drugs are limited, and the development of new drugs is extremely challenging. As an alternative approach, we focused on a combinational treatment strategy and found that 5-O-mycaminosyltylonolide (OMT) showed potent antibacterial activity against P. aeruginosa in the presence of an efflux pump inhibitor, phenylalanine-arginine beta-naphthylamide (PAβN). In this report, we prepared a PAβN derivative and compared the potentiation activity of OMT by PAβNs against multidrug-resistant P. aeruginosa clinical isolates.

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来源期刊

Journal of Antibiotics 医学-免疫学

CiteScore

6.60

自引率

3.00%

发文量

审稿时长

1 months

期刊介绍： The Journal of Antibiotics seeks to promote research on antibiotics and related types of biologically active substances and publishes Articles, Review Articles, Brief Communication, Correspondence and other specially commissioned reports. The Journal of Antibiotics accepts papers on biochemical, chemical, microbiological and pharmacological studies. However, studies regarding human therapy do not fall under the journal’s scope. Contributions regarding recently discovered antibiotics and biologically active microbial products are particularly encouraged. Topics of particular interest within the journal''s scope include, but are not limited to, those listed below: Discovery of new antibiotics and related types of biologically active substances Production, isolation, characterization, structural elucidation, chemical synthesis and derivatization, biological activities, mechanisms of action, and structure-activity relationships of antibiotics and related types of biologically active substances Biosynthesis, bioconversion, taxonomy and genetic studies on producing microorganisms, as well as improvement of production of antibiotics and related types of biologically active substances Novel physical, chemical, biochemical, microbiological or pharmacological methods for detection, assay, determination, structural elucidation and evaluation of antibiotics and related types of biologically active substances Newly found properties, mechanisms of action and resistance-development of antibiotics and related types of biologically active substances.