异尿酸原靶向las, rhl和Pqs群体感应系统,以减轻铜绿假单胞菌的毒力和感染。

IF 4.2 2区 生物学 Q2 MICROBIOLOGY
Wenxu Song, Zhiying Tian, Yanhong Wang, Yanjie Yin, Haixiang Zhang, Cuixiang Xu, Lixin Shen
{"title":"异尿酸原靶向las, rhl和Pqs群体感应系统,以减轻铜绿假单胞菌的毒力和感染。","authors":"Wenxu Song, Zhiying Tian, Yanhong Wang, Yanjie Yin, Haixiang Zhang, Cuixiang Xu, Lixin Shen","doi":"10.1186/s12866-025-04298-5","DOIUrl":null,"url":null,"abstract":"<p><p>Pseudomonas aeruginosa is an opportunistic pathogen with high antibiotic resistance, often causing hard-to-treat infections. Its quorum sensing (QS) system regulates virulence and drug resistance. Targeting quorum sensing via QS inhibitors is a promising strategy to combat such infections. In this study, isoliquiritigenin, a natural chalcone compound, could inhibit QS-related gene expression (lasR, lasI, rhlR, rhlI, pqsA, pqsR, lasA, rhlA, phzA1) and reduced virulence factor production of Pseudomonas aeruginosa PAO1, including protease, elastase, pyocyanin, rhamnolipid, biofilm formation and motility at subinhibitory concentrations of 50 and 100 µg/mL. The pathogenicity of PAO1 could be also attenuated by isoliquiritigenin at the tested concentrations evidenced by in vitro and vivo infection analysis via Chinese cabbage, Drosophila melanogaster, and Caenorhabditis elegans modles. Isoliquiritigenin might exhibit QSI property by targeting the las, rhl, and pqs systems based on the molecular docking analysis and the infection analysis in mutants. As a novel QSI, isoliquiritigenin develop less tendency drug resistance to PAO1, at least during the 20 generations tested. Moreover, isoliquiritigenin could increase the sensitivity of P. aeruginosa to aminoglycosides of kanamycin, amikacin or tobramycin, enhancing P. aeruginosa infection treatment. Therefore, isoliquiritigenin could function as a potential QSI against P. aeruginosa infection, either separately or synergistically combined with aminoglycosides antibiotics.</p>","PeriodicalId":9233,"journal":{"name":"BMC Microbiology","volume":"25 1","pages":"580"},"PeriodicalIF":4.2000,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12462295/pdf/","citationCount":"0","resultStr":"{\"title\":\"Isoliquiritigenin targets las, rhl, and Pqs quorum sensing systems to mitigate the virulence and infection of Pseudomonas aeruginosa.\",\"authors\":\"Wenxu Song, Zhiying Tian, Yanhong Wang, Yanjie Yin, Haixiang Zhang, Cuixiang Xu, Lixin Shen\",\"doi\":\"10.1186/s12866-025-04298-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Pseudomonas aeruginosa is an opportunistic pathogen with high antibiotic resistance, often causing hard-to-treat infections. Its quorum sensing (QS) system regulates virulence and drug resistance. Targeting quorum sensing via QS inhibitors is a promising strategy to combat such infections. In this study, isoliquiritigenin, a natural chalcone compound, could inhibit QS-related gene expression (lasR, lasI, rhlR, rhlI, pqsA, pqsR, lasA, rhlA, phzA1) and reduced virulence factor production of Pseudomonas aeruginosa PAO1, including protease, elastase, pyocyanin, rhamnolipid, biofilm formation and motility at subinhibitory concentrations of 50 and 100 µg/mL. The pathogenicity of PAO1 could be also attenuated by isoliquiritigenin at the tested concentrations evidenced by in vitro and vivo infection analysis via Chinese cabbage, Drosophila melanogaster, and Caenorhabditis elegans modles. Isoliquiritigenin might exhibit QSI property by targeting the las, rhl, and pqs systems based on the molecular docking analysis and the infection analysis in mutants. As a novel QSI, isoliquiritigenin develop less tendency drug resistance to PAO1, at least during the 20 generations tested. Moreover, isoliquiritigenin could increase the sensitivity of P. aeruginosa to aminoglycosides of kanamycin, amikacin or tobramycin, enhancing P. aeruginosa infection treatment. Therefore, isoliquiritigenin could function as a potential QSI against P. aeruginosa infection, either separately or synergistically combined with aminoglycosides antibiotics.</p>\",\"PeriodicalId\":9233,\"journal\":{\"name\":\"BMC Microbiology\",\"volume\":\"25 1\",\"pages\":\"580\"},\"PeriodicalIF\":4.2000,\"publicationDate\":\"2025-09-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12462295/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"BMC Microbiology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1186/s12866-025-04298-5\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Microbiology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s12866-025-04298-5","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

铜绿假单胞菌是一种具有高抗生素耐药性的机会性病原体,经常引起难以治疗的感染。其群体感应(QS)系统调节毒力和耐药性。通过QS抑制剂靶向群体感应是对抗此类感染的有希望的策略。本研究发现,天然查尔酮类化合物异尿酸原素(isoliquirigenin)在50和100 μ g/mL的亚抑制浓度下,可抑制qs相关基因(lasR、lasI、rhlR、rhlI、pqsA、pqsR、lasA、rhlA、phzA1)的表达,降低铜绿假单胞菌PAO1的毒力因子产生,包括蛋白酶、弹性酶、花青素、鼠李糖脂、生物膜形成和活力。通过白菜、黑腹果蝇和秀丽隐杆线虫模型的体外和体内感染分析表明,在所测浓度下,异尿酸原素也能减弱PAO1的致病性。基于分子对接分析和突变体的感染分析,异异黄酮原素可能通过靶向las、rhl和pqs系统而表现出QSI特性。异异藜素作为一种新型QSI,至少在20代的测试中,对PAO1的耐药倾向较小。此外,异尿酸原可提高铜绿假单胞菌对卡那霉素、阿米卡星或妥布霉素氨基糖苷类药物的敏感性,促进铜绿假单胞菌感染的治疗。因此,无论是单独使用还是与氨基糖苷类抗生素协同使用,异尿酸原素都可能作为抗铜绿假单胞菌感染的潜在QSI。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Isoliquiritigenin targets las, rhl, and Pqs quorum sensing systems to mitigate the virulence and infection of Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an opportunistic pathogen with high antibiotic resistance, often causing hard-to-treat infections. Its quorum sensing (QS) system regulates virulence and drug resistance. Targeting quorum sensing via QS inhibitors is a promising strategy to combat such infections. In this study, isoliquiritigenin, a natural chalcone compound, could inhibit QS-related gene expression (lasR, lasI, rhlR, rhlI, pqsA, pqsR, lasA, rhlA, phzA1) and reduced virulence factor production of Pseudomonas aeruginosa PAO1, including protease, elastase, pyocyanin, rhamnolipid, biofilm formation and motility at subinhibitory concentrations of 50 and 100 µg/mL. The pathogenicity of PAO1 could be also attenuated by isoliquiritigenin at the tested concentrations evidenced by in vitro and vivo infection analysis via Chinese cabbage, Drosophila melanogaster, and Caenorhabditis elegans modles. Isoliquiritigenin might exhibit QSI property by targeting the las, rhl, and pqs systems based on the molecular docking analysis and the infection analysis in mutants. As a novel QSI, isoliquiritigenin develop less tendency drug resistance to PAO1, at least during the 20 generations tested. Moreover, isoliquiritigenin could increase the sensitivity of P. aeruginosa to aminoglycosides of kanamycin, amikacin or tobramycin, enhancing P. aeruginosa infection treatment. Therefore, isoliquiritigenin could function as a potential QSI against P. aeruginosa infection, either separately or synergistically combined with aminoglycosides antibiotics.

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
BMC Microbiology
BMC Microbiology 生物-微生物学
CiteScore
7.20
自引率
0.00%
发文量
280
审稿时长
3 months
期刊介绍: BMC Microbiology is an open access, peer-reviewed journal that considers articles on analytical and functional studies of prokaryotic and eukaryotic microorganisms, viruses and small parasites, as well as host and therapeutic responses to them and their interaction with the environment.
×
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
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
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 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信