Zhao-Sheng Zhang, Zhe He, Yu Shi, Mingming Guan, Dong-Sheng Zhao, Di Zhu, Lan-Tu Xiong, Yasheng Li, Xin Deng, Zi-Ning Cui
{"title":"Structure-Based Discovery of Symmetric Disulfides from Garlic Extract as Pseudomonas aeruginosa Quorum Sensing Inhibitors","authors":"Zhao-Sheng Zhang, Zhe He, Yu Shi, Mingming Guan, Dong-Sheng Zhao, Di Zhu, Lan-Tu Xiong, Yasheng Li, Xin Deng, Zi-Ning Cui","doi":"10.1021/acs.jafc.4c04404","DOIUrl":null,"url":null,"abstract":"Microorganisms are the most common cause of food spoilage. <i>Pseudomonas aeruginosa</i> is a common foodborne pathogen that causes food spoilage and poses a serious threat to food safety. As a crucial target in antitoxicity strategies, the quorum sensing (QS) system shows promising potential for further development. The garlic extract diallyl disulfide exhibits inhibitory activity against the QS system of <i>P. aeruginosa</i>, with disulfide bonds serving as the active component. However, the biological activity of other symmetric disulfides has not been investigated in this capacity. The study synthesized 39 disulfide bond-containing analogs and evaluated their activity as quorum sensing inhibitors (QSIs). The results showed that <i>p</i>-hydroxyphenyl substitution can replace the allyl groups while maintaining strong biological activity. The virulence factors production was reduced by compound <b>2i</b>, with the strongest inhibitory effect being observed on elastase production. Synergistic inhibition was observed in the presence of antibiotics like ciprofloxacin and tobramycin. <b>2i</b> successfully inhibited <i>P. aeruginosa</i> infection in the <i>Galleria mellonella</i> larvae model. Primary mechanism studies using transcriptome, surface plasmon resonance and molecular docking suggested that <b>2i</b> inhibits the QS system by targeting the LasR protein. Thus, compound <b>2i</b> could be used in developing QSIs for the control of <i>P. aeruginosa</i> infections.","PeriodicalId":41,"journal":{"name":"Journal of Agricultural and Food Chemistry","volume":null,"pages":null},"PeriodicalIF":5.7000,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Agricultural and Food Chemistry","FirstCategoryId":"97","ListUrlMain":"https://doi.org/10.1021/acs.jafc.4c04404","RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"AGRICULTURE, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
Microorganisms are the most common cause of food spoilage. Pseudomonas aeruginosa is a common foodborne pathogen that causes food spoilage and poses a serious threat to food safety. As a crucial target in antitoxicity strategies, the quorum sensing (QS) system shows promising potential for further development. The garlic extract diallyl disulfide exhibits inhibitory activity against the QS system of P. aeruginosa, with disulfide bonds serving as the active component. However, the biological activity of other symmetric disulfides has not been investigated in this capacity. The study synthesized 39 disulfide bond-containing analogs and evaluated their activity as quorum sensing inhibitors (QSIs). The results showed that p-hydroxyphenyl substitution can replace the allyl groups while maintaining strong biological activity. The virulence factors production was reduced by compound 2i, with the strongest inhibitory effect being observed on elastase production. Synergistic inhibition was observed in the presence of antibiotics like ciprofloxacin and tobramycin. 2i successfully inhibited P. aeruginosa infection in the Galleria mellonella larvae model. Primary mechanism studies using transcriptome, surface plasmon resonance and molecular docking suggested that 2i inhibits the QS system by targeting the LasR protein. Thus, compound 2i could be used in developing QSIs for the control of P. aeruginosa infections.
期刊介绍:
The Journal of Agricultural and Food Chemistry publishes high-quality, cutting edge original research representing complete studies and research advances dealing with the chemistry and biochemistry of agriculture and food. The Journal also encourages papers with chemistry and/or biochemistry as a major component combined with biological/sensory/nutritional/toxicological evaluation related to agriculture and/or food.