Structure-Based Discovery of Symmetric Disulfides from Garlic Extract as Pseudomonas aeruginosa Quorum Sensing Inhibitors,Journal of Agricultural and Food Chemistry

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Structure-Based Discovery of Symmetric Disulfides from Garlic Extract as Pseudomonas aeruginosa Quorum Sensing Inhibitors
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2024-09-04 , DOI: 10.1021/acs.jafc.4c04404
Zhao-Sheng Zhang ₁ , Zhe He ₁ , Yu Shi _{1,

2} , Mingming Guan ₁ , Dong-Sheng Zhao ₃ , Di Zhu ₁ , Lan-Tu Xiong ₁ , Yasheng Li ₄ , Xin Deng _{5,

6} , Zi-Ning Cui ₁

Affiliation

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.

中文翻译：

基于结构的大蒜提取物对称二硫化物作为铜绿假单胞菌群体感应抑制剂的发现

微生物是食物腐败的最常见原因。铜绿假单胞菌是一种常见的食源性致病菌，可导致食品腐败变质，对食品安全构成严重威胁。作为抗毒性策略的关键目标，群体感应（QS）系统显示出进一步发展的广阔潜力。大蒜提取物二烯丙基二硫醚对铜绿假单胞菌QS系统具有抑制活性，其活性成分为二硫键。然而，其他对称二硫化物的生物活性尚未在这方面进行研究。该研究合成了 39 种含有二硫键的类似物，并评估了它们作为群体感应抑制剂 (QSI) 的活性。结果表明，对羟基苯基取代可以取代烯丙基，同时保持较强的生物活性。化合物2i减少了毒力因子的产生，观察到对弹性蛋白酶产生的最强抑制作用。在环丙沙星和妥布霉素等抗生素存在下观察到协同抑制作用。 2i成功抑制大蜡螟幼虫模型中的铜绿假单胞菌感染。使用转录组、表面等离子共振和分子对接的主要机制研究表明， 2i通过靶向 LasR 蛋白来抑制 QS 系统。因此，化合物2i可用于开发用于控制铜绿假单胞菌感染的 QSI。

更新日期：2024-09-04

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