Identification of AI-2 Quorum Sensing Inhibitors in Vibrio harveyi Through Structure-Based Virtual Screening
Quorum sensing (QS) is a cell-to-cell communication system that regulates gene expression as a result of the production and perception of signal molecules called autoinducers (AIs). AI-2 is a QS autoinducer produced by both Gram-negative and Gram-positive bacteria, in which it regulates intraspecies and interspecies communication. The identification of QS inhibitors is considered a promising strategy for the development of anti-virulence drugs with reduced selective pressure for resistance. Here we describe a high-throughput virtual screening approach to identify AI-2 quorum sensing inhibitors on the basis of Vibrio harveyi LuxPQ crystal structure. Seven potent inhibitors with IC50 values in the micromolar range were selected with no effect or low effect on V. harveyi growth rate.
Key wordsAI-2 Vibrio harveyi LuxPQ Quorum sensing inhibitors Virtual screening
This project was funded by the National Program on Key Basic Research Project of China (No. 2013CB734002), the National Natural Science Foundation of China (No. 81370085 and 81001362), the Qilu Professorship at Shandong University, and the Taishan Scholarship Program at Shandong Province.
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