Organosulfur Scaffolds as Quorum Sensing and Biofilm Modulators in Gram-Negative Bacteria

Abstract Quorum sensing (QS) is a cell-density-dependent communication system that coordinates bacterial virulence, biofilm formation, motility, and stress adaptation, making it a compelling target for antivirulence intervention. Due to the possibility of sulfonyl (-SO₂-) and sulfinyl (-S=O-) functional groups to impart specific electronic and steric properties that can modulate bacterial signaling and receptor interactions, organosulfur compounds are increasingly gaining attention. This review highlights recent advances in the development of sulfonyl- and sulfinyl-containing organosulfur compounds as modulators of QS and biofilm formation in clinically relevant Gram-negative pathogens. Both natural and synthetic quorum-sensing inhibitors are considered, with activity directed toward LuxR-type regulators, diffusible signal factor (DSF)-mediated systems, and the Las/Rhl networks of Gram-negative bacteria, including Pseudomonas aeruginosa, Vibrio spp., Chromobacterium violaceum, and Xylella fastidiosa. Emphasis is placed on emerging structure-activity relationships and mechanistic insights derived from biochemical and computational studies. Key challenges, including resistance potential, pharmacological constraints, and delivery considerations, are also discussed. Together, we provide an integrated microbiological and medicinal chemistry perspective for the rational development of organosulfur-based strategies to attenuate QS-regulated pathogenicity.