Natural Lactone‐Based Quorum Sensing Inhibitors Attenuate Virulence in Pseudomonas aeruginosa

Abstract

Natural lactones represent a promising anti‐virulence strategy against Pseudomonas aeruginosa by targeting quorum‐sensing (QS) pathways. In this work, we investigate γ‐caprolactone (Capro), γ‐octalactone (Octa), γ‐decalactone (GDL), δ‐decalactone (DDL), and a laboratory‐generated lactone mixture (Lx) as modulators of QS‐regulated virulence. Treatment with γ‐decalactone and engineered lactone formulations significantly downregulated rhlR expression (∼twofold) and suppressed pyocyanin and rhamnolipid production. At 48 h, lactone exposure reduced extracellular virulence factors by up to 74.81% (pyocyanin) and 49.08% (rhamnolipids), indicating effective disruption of quorum sensing signaling. Collectively, these findings demonstrate that biotransformation‐derived lactones attenuate virulence programs in P. aeruginosa, highlighting their potential as quorum sensing inhibitors for managing biofilm‐associated infections.