Effect of Autoinducer-2 Quorum Sensing Inhibitor on Interspecies Quorum Sensing

作者：Kai Jiang, Yijie Xu, Bo Yuan, Yuandong Yue, Meihua Zhao, Rui Luo, Hao Wu, Lei Wang, Yuanyuan Zhang, Junhai Xiao, Feng Lin · 发表于：Frontiers in Microbiology · 年份：2022 · DOI：10.3389/fmicb.2022.791802 · 被引用次数：42 · 研究领域：Bacterial biofilms and quorum sensing、Antibiotic Resistance in Bacteria、Vibrio bacteria research studies

Bacterial drug resistance caused by overuse and misuse of antibiotics is common, especially in clinical multispecies infections. It is of great significance to discover novel agents to treat clinical bacterial infections. Studies have demonstrated that autoinducer-2 (AI-2), a signal molecule in quorum sensing (QS), plays an important role in communication among multiple bacterial species and bacterial drug-resistance. Previously, 14 AI-2 inhibited compounds were selected through virtual screening by using the AI-2 receptor protein LuxP as a target. Here, we used Vibrio harveyi BB170 as a reporter strain for the preliminary screening of 14 inhibitors and compound Str7410 had higher AI-2 QS inhibition activity (IC 50 = 0.3724 ± 0.1091 μM). Then, co-culture of Pseudomonas aeruginosa PAO1 with Staphylococcus aureus ATCC 25923 was used to evaluate the inhibitory effects of Str7410 on multispecies infection in vitro and in vivo . In vitro , Str7410 significantly inhibited the formation of mixed bacterial biofilms. Meanwhile, the combination of Str7410 with meropenem trihydrate (MEPM) significantly improved the susceptibility of mixed-species-biofilm cells to the antibiotic. In vivo , Str7410 significantly increased the survival rate of wild-type Caenorhabditis elegans N2 co-infected by P. aeruginosa PAO1 and S. aureus ATCC 25923. Real-time quantitative PCR analysis showed that Str7410 reduced virulence factor (pyocyanin and elastase) production and swarming motility of P. aeruginos...