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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. aeruginosa  PAO1 by downregulating the expression of QS-related genes in strain PAO1 in co-culture with  S. aureus  ATCC 25923. Compound Str7410 is a candidate agent for treating drug-resistant multispecies infections. The work described here provides a strategy for discovering novel antibacterial drugs.

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