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.