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Structure‐Based Discovery and Experimental Verification of Novel AI‐2 Quorum Sensing Inhibitors against Vibrio harveyi
Author(s) -
Li Minyong,
Ni Nanting,
Chou HanTing,
Lu ChungDar,
Tai Phang C.,
Wang Binghe
Publication year - 2008
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200800076
Subject(s) - quorum sensing , vibrio harveyi , biofilm , virulence , swarming motility , microbiology and biotechnology , virtual screening , biology , secretion , bacteria , computational biology , chemistry , drug discovery , vibrio , biochemistry , gene , genetics
Abstract Quorum sensing has been implicated in the control of pathologically relevant bacterial behavior such as secretion of virulence factors, biofilm formation, sporulation, and swarming motility. The AI‐2 quorum sensing pathway is found in both Gram‐positive and Gram‐negative bacteria. Therefore, antagonizing AI‐2 quorum sensing is a possible approach to modifying bacterial behaviour. However, efforts in developing inhibitors of AI‐2‐mediated quorum sensing are especially lacking. High‐throughput virtual screening using the V. harveyi LuxP crystal structure identified two compounds that were found to antagonize AI‐2‐mediated quorum sensing in V. harveyi without cytotoxicity. The sulfone functionality of these inhibitors was identified as critical to their ability to mimic the natural ligand in their interactions with Arg 215 and Arg 310 of the active site.