西洛他唑是一种很有前途的通过破坏法定人数感应来抗假单胞菌毒力的药物。

IF 3.5 3区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY AMB Express Pub Date : 2024-08-01 DOI:10.1186/s13568-024-01740-1
Mohammed W Al-Rabia, Hani Z Asfour, Nabil A Alhakamy, Mohammed A Bazuhair, Tarek S Ibrahim, Hisham A Abbas, Basem Mansour, Wael A H Hegazy, Noura M Seleem
{"title":"西洛他唑是一种很有前途的通过破坏法定人数感应来抗假单胞菌毒力的药物。","authors":"Mohammed W Al-Rabia, Hani Z Asfour, Nabil A Alhakamy, Mohammed A Bazuhair, Tarek S Ibrahim, Hisham A Abbas, Basem Mansour, Wael A H Hegazy, Noura M Seleem","doi":"10.1186/s13568-024-01740-1","DOIUrl":null,"url":null,"abstract":"<p><p>Resistance to antibiotics is a critical growing public health problem that desires urgent action to combat. To avoid the stress on bacterial growth that evokes the resistance development, anti-virulence agents can be an attractive strategy as they do not target bacterial growth. Quorum sensing (QS) systems play main roles in controlling the production of diverse virulence factors and biofilm formation in bacteria. Thus, interfering with QS systems could result in mitigation of the bacterial virulence. Cilostazol is an antiplatelet and a vasodilator FDA approved drug. This study aimed to evaluate the anti-virulence activities of cilostazol in the light of its possible interference with QS systems in Pseudomonas aeruginosa. Additionally, the study examines cilostazol's impact on the bacterium's ability to induce infection in vivo, using sub-inhibitory concentrations to minimize the risk of resistance development. In this context, the biofilm formation, the production of virulence factors and influence on the in vivo ability to induce infection were assessed in the presence of cilostazol at sub-inhibitory concentration. Furthermore, the outcome of combination with antibiotics was evaluated. Cilostazol interfered with biofilm formation in P. aeruginosa. Moreover, swarming motility, biofilm formation and production of virulence factors were significantly diminished. Histopathological investigation revealed that liver, spleen and kidney tissues damage was abolished in mice injected with cilostazol-treated bacteria. Cilostazol exhibited a synergistic outcome when used in combination with antibiotics. At the molecular level, cilostazol downregulated the QS genes and showed considerable affinity to QS receptors. In conclusion, Cilostazol could be used as adjunct therapy with antibiotics for treating Pseudomonal infections. This research highlights cilostazol's potential to combat bacterial infections by targeting virulence mechanisms, reducing the risk of antibiotic resistance, and enhancing treatment efficacy against P. aeruginosa. These findings open avenues for repurposing existing drugs, offering new, safer, and more effective infection control strategies.</p>","PeriodicalId":7537,"journal":{"name":"AMB Express","volume":null,"pages":null},"PeriodicalIF":3.5000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11294311/pdf/","citationCount":"0","resultStr":"{\"title\":\"Cilostazol is a promising anti-pseudomonal virulence drug by disruption of quorum sensing.\",\"authors\":\"Mohammed W Al-Rabia, Hani Z Asfour, Nabil A Alhakamy, Mohammed A Bazuhair, Tarek S Ibrahim, Hisham A Abbas, Basem Mansour, Wael A H Hegazy, Noura M Seleem\",\"doi\":\"10.1186/s13568-024-01740-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Resistance to antibiotics is a critical growing public health problem that desires urgent action to combat. To avoid the stress on bacterial growth that evokes the resistance development, anti-virulence agents can be an attractive strategy as they do not target bacterial growth. Quorum sensing (QS) systems play main roles in controlling the production of diverse virulence factors and biofilm formation in bacteria. Thus, interfering with QS systems could result in mitigation of the bacterial virulence. Cilostazol is an antiplatelet and a vasodilator FDA approved drug. This study aimed to evaluate the anti-virulence activities of cilostazol in the light of its possible interference with QS systems in Pseudomonas aeruginosa. Additionally, the study examines cilostazol's impact on the bacterium's ability to induce infection in vivo, using sub-inhibitory concentrations to minimize the risk of resistance development. In this context, the biofilm formation, the production of virulence factors and influence on the in vivo ability to induce infection were assessed in the presence of cilostazol at sub-inhibitory concentration. Furthermore, the outcome of combination with antibiotics was evaluated. Cilostazol interfered with biofilm formation in P. aeruginosa. Moreover, swarming motility, biofilm formation and production of virulence factors were significantly diminished. Histopathological investigation revealed that liver, spleen and kidney tissues damage was abolished in mice injected with cilostazol-treated bacteria. Cilostazol exhibited a synergistic outcome when used in combination with antibiotics. At the molecular level, cilostazol downregulated the QS genes and showed considerable affinity to QS receptors. In conclusion, Cilostazol could be used as adjunct therapy with antibiotics for treating Pseudomonal infections. This research highlights cilostazol's potential to combat bacterial infections by targeting virulence mechanisms, reducing the risk of antibiotic resistance, and enhancing treatment efficacy against P. aeruginosa. These findings open avenues for repurposing existing drugs, offering new, safer, and more effective infection control strategies.</p>\",\"PeriodicalId\":7537,\"journal\":{\"name\":\"AMB Express\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2024-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11294311/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"AMB Express\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://doi.org/10.1186/s13568-024-01740-1\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"AMB Express","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1186/s13568-024-01740-1","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

抗生素耐药性是一个日益严重的公共卫生问题,需要采取紧急行动加以解决。为了避免细菌生长受到压力而产生抗药性,抗病毒剂是一种有吸引力的策略,因为它们不针对细菌生长。法定量感应(QS)系统在控制细菌产生各种毒力因子和形成生物膜方面发挥着主要作用。因此,干扰 QS 系统可减轻细菌的毒力。西洛他唑是一种经 FDA 批准的抗血小板和血管扩张药物。本研究旨在评估西洛他唑可能干扰铜绿假单胞菌 QS 系统的抗病毒活性。此外,研究还考察了西洛他唑对细菌体内诱导感染能力的影响,使用亚抑制浓度以最大限度地降低耐药性产生的风险。在这种情况下,在亚抑制浓度的西洛他唑存在下,对生物膜的形成、毒力因子的产生以及对体内诱导感染能力的影响进行了评估。此外,还评估了与抗生素联合使用的效果。西洛他唑干扰了铜绿假单胞菌生物膜的形成。此外,蜂拥运动、生物膜的形成和毒力因子的产生也明显减少。组织病理学调查显示,注射了西洛他唑处理过的细菌的小鼠的肝、脾和肾组织损伤消失。西洛他唑与抗生素联合使用时可产生协同效应。在分子水平上,西洛他唑下调了 QS 基因,并与 QS 受体表现出相当大的亲和力。总之,西洛他唑可作为抗生素的辅助疗法用于治疗假丝酵母菌感染。这项研究强调了西洛他唑通过靶向毒力机制、降低抗生素耐药性风险和提高对铜绿假单胞菌的疗效来抗击细菌感染的潜力。这些发现为现有药物的再利用开辟了道路,提供了更安全、更有效的新型感染控制策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

摘要图片

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Cilostazol is a promising anti-pseudomonal virulence drug by disruption of quorum sensing.

Resistance to antibiotics is a critical growing public health problem that desires urgent action to combat. To avoid the stress on bacterial growth that evokes the resistance development, anti-virulence agents can be an attractive strategy as they do not target bacterial growth. Quorum sensing (QS) systems play main roles in controlling the production of diverse virulence factors and biofilm formation in bacteria. Thus, interfering with QS systems could result in mitigation of the bacterial virulence. Cilostazol is an antiplatelet and a vasodilator FDA approved drug. This study aimed to evaluate the anti-virulence activities of cilostazol in the light of its possible interference with QS systems in Pseudomonas aeruginosa. Additionally, the study examines cilostazol's impact on the bacterium's ability to induce infection in vivo, using sub-inhibitory concentrations to minimize the risk of resistance development. In this context, the biofilm formation, the production of virulence factors and influence on the in vivo ability to induce infection were assessed in the presence of cilostazol at sub-inhibitory concentration. Furthermore, the outcome of combination with antibiotics was evaluated. Cilostazol interfered with biofilm formation in P. aeruginosa. Moreover, swarming motility, biofilm formation and production of virulence factors were significantly diminished. Histopathological investigation revealed that liver, spleen and kidney tissues damage was abolished in mice injected with cilostazol-treated bacteria. Cilostazol exhibited a synergistic outcome when used in combination with antibiotics. At the molecular level, cilostazol downregulated the QS genes and showed considerable affinity to QS receptors. In conclusion, Cilostazol could be used as adjunct therapy with antibiotics for treating Pseudomonal infections. This research highlights cilostazol's potential to combat bacterial infections by targeting virulence mechanisms, reducing the risk of antibiotic resistance, and enhancing treatment efficacy against P. aeruginosa. These findings open avenues for repurposing existing drugs, offering new, safer, and more effective infection control strategies.

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
AMB Express
AMB Express BIOTECHNOLOGY & APPLIED MICROBIOLOGY-
CiteScore
7.20
自引率
2.70%
发文量
141
审稿时长
13 weeks
期刊介绍: AMB Express is a high quality journal that brings together research in the area of Applied and Industrial Microbiology with a particular interest in ''White Biotechnology'' and ''Red Biotechnology''. The emphasis is on processes employing microorganisms, eukaryotic cell cultures or enzymes for the biosynthesis, transformation and degradation of compounds. This includes fine and bulk chemicals, polymeric compounds and enzymes or other proteins. Downstream processes are also considered. Integrated processes combining biochemical and chemical processes are also published.
期刊最新文献
Compatibility and antimicrobial activity of silver nanoparticles synthesized using Lycopersicon esculentum peels. Scaling up production of cephalosporin C by Acremonium chrysogenum W42-I in a fermenter using submerged fermentation. Nano selenium in broiler feeding: physiological roles and nutritional effects. Crotalaria madurensis flavonol glycosides' antibacterial activity against Staphylococcus aureus. In vitro antibacterial activity of photoactivated flavonoid glycosides against Acinetobacter baumannii.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1