Natural Lactone-Based Quorum Sensing Inhibitors Attenuate Virulence in Pseudomonas aeruginosa.

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.