() is an opportunistic human pathogen that forms biofilms and produces virulence factors quorum sensing (QS). Blocking the QS system in is an excellent strategy to reduce biofilm formation and the production of virulence factors. RhlR plays an essential role in the QS system of . We synthesized 55 analogues based on the chemical structure of 4-gingerol and evaluated their RhlR inhibitory activities using the cell-based reporter strain assay. Comprehensive structure-activity relationship studies identified the alkynyl ketone as the most potent RhlR antagonist. This compound displayed selective RhlR antagonism over LasR and PqsR, strong inhibition of biofilm formation, and reduced production of virulence factors in . Furthermore, the survival rate of larvae treated with greatly improved. Therefore, compound , a pure RhlR antagonist, can be utilized for developing QS-modulating molecules in the control of infections.
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