Murepavadin 通过抑制药物外流增强环丙沙星对铜绿假单胞菌的杀灭效力

IF 4.3 2区医学 Q1 INFECTIOUS DISEASES

Antibiotics-Basel Pub Date : 2024-08-26 DOI:10.3390/antibiotics13090810

Xiaoya Wei, Dandan Zhou, Congjuan Xu, Ping Chen, Shuiping Chen, Zhihui Cheng, Yongxin Jin, Shouguang Jin, Weihui Wu

{"title":"Murepavadin 通过抑制药物外流增强环丙沙星对铜绿假单胞菌的杀灭效力","authors":"Xiaoya Wei, Dandan Zhou, Congjuan Xu, Ping Chen, Shuiping Chen, Zhihui Cheng, Yongxin Jin, Shouguang Jin, Weihui Wu","doi":"10.3390/antibiotics13090810","DOIUrl":null,"url":null,"abstract":"Pseudomonas aeruginosa is a multidrug-resistant Gram-negative pathogen and one of the leading causes of ventilator-associated pneumonia and infections in patients with chronic obstructive pulmonary disease and cystic fibrosis. Murepavadin is a peptidomimetic that specifically targets outer-membrane lipopolysaccharide transport protein LptD of P. aeruginosa. In this study, we find that murepavadin enhances the bactericidal efficacy of ciprofloxacin. We further demonstrate that murepavadin increases intracellular accumulation of ciprofloxacin by suppressing drug efflux. In addition, the murepavadin-ciprofloxacin combination exhibits a synergistic bactericidal effect in an acute murine pneumonia model. In conclusion, our results identify an effective drug combination for the treatment of P. aeruginosa infections.","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":null,"pages":null},"PeriodicalIF":4.3000,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11429200/pdf/","citationCount":"0","resultStr":"{\"title\":\"Murepavadin Enhances the Killing Efficacy of Ciprofloxacin against Pseudomonas aeruginosa by Inhibiting Drug Efflux.\",\"authors\":\"Xiaoya Wei, Dandan Zhou, Congjuan Xu, Ping Chen, Shuiping Chen, Zhihui Cheng, Yongxin Jin, Shouguang Jin, Weihui Wu\",\"doi\":\"10.3390/antibiotics13090810\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Pseudomonas aeruginosa is a multidrug-resistant Gram-negative pathogen and one of the leading causes of ventilator-associated pneumonia and infections in patients with chronic obstructive pulmonary disease and cystic fibrosis. Murepavadin is a peptidomimetic that specifically targets outer-membrane lipopolysaccharide transport protein LptD of P. aeruginosa. In this study, we find that murepavadin enhances the bactericidal efficacy of ciprofloxacin. We further demonstrate that murepavadin increases intracellular accumulation of ciprofloxacin by suppressing drug efflux. In addition, the murepavadin-ciprofloxacin combination exhibits a synergistic bactericidal effect in an acute murine pneumonia model. In conclusion, our results identify an effective drug combination for the treatment of P. aeruginosa infections.\",\"PeriodicalId\":54246,\"journal\":{\"name\":\"Antibiotics-Basel\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2024-08-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11429200/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Antibiotics-Basel\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3390/antibiotics13090810\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"INFECTIOUS DISEASES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Antibiotics-Basel","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3390/antibiotics13090810","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}

引用次数: 0

摘要

铜绿假单胞菌是一种具有多重耐药性的革兰氏阴性病原体，是呼吸机相关性肺炎和慢性阻塞性肺病及囊性纤维化患者感染的主要病因之一。Murepavadin 是一种肽模拟物，专门针对铜绿假单胞菌的外膜脂多糖转运蛋白 LptD。在这项研究中，我们发现金刚烷胺能增强环丙沙星的杀菌效果。我们进一步证明，金葡菌胺通过抑制药物外流增加了环丙沙星在细胞内的蓄积。此外，在急性小鼠肺炎模型中，murepavadin-环丙沙星复方制剂具有协同杀菌作用。总之，我们的研究结果确定了一种治疗铜绿假单胞菌感染的有效联合用药。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

Murepavadin Enhances the Killing Efficacy of Ciprofloxacin against Pseudomonas aeruginosa by Inhibiting Drug Efflux.

Pseudomonas aeruginosa is a multidrug-resistant Gram-negative pathogen and one of the leading causes of ventilator-associated pneumonia and infections in patients with chronic obstructive pulmonary disease and cystic fibrosis. Murepavadin is a peptidomimetic that specifically targets outer-membrane lipopolysaccharide transport protein LptD of P. aeruginosa. In this study, we find that murepavadin enhances the bactericidal efficacy of ciprofloxacin. We further demonstrate that murepavadin increases intracellular accumulation of ciprofloxacin by suppressing drug efflux. In addition, the murepavadin-ciprofloxacin combination exhibits a synergistic bactericidal effect in an acute murine pneumonia model. In conclusion, our results identify an effective drug combination for the treatment of P. aeruginosa infections.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Antibiotics-Basel Pharmacology, Toxicology and Pharmaceutics-General Pharmacology, Toxicology and Pharmaceutics

CiteScore

7.30

自引率

14.60%

发文量

1547

审稿时长

11 weeks

期刊介绍： Antibiotics (ISSN 2079-6382) is an open access, peer reviewed journal on all aspects of antibiotics. Antibiotics is a multi-disciplinary journal encompassing the general fields of biochemistry, chemistry, genetics, microbiology and pharmacology. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. Therefore, there is no restriction on the length of papers.