| Summary: | <i>Pseudomonas</i> <i>aeruginosa</i> (<i>P</i>. <i>aeruginosa</i>) is an opportunistic gram-negative pathogen that can cause various infections, particularly in patients with compromised host defenses. <i>P</i>. <i>aeruginosa</i> forms biofilms and produces virulence factors through quorum sensing (QS) network, resulting in resistance to antibiotics. RhlI/RhlR, one of key QS systems in <i>P</i>. <i>aeruginosa</i>, is considered an attractive target for inhibiting biofilm formation and attenuating virulence factors. Several recent studies examined small molecules targeting the RhlI/RhlR system and their in vitro and in vivo biological activities. In this review, RhlR-targeted modulators, including agonists and antagonists, are discussed with particular focus on structure-activity relationship studies and outlook for next-generation anti-biofilm agents.
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