Lactones as promising biofilm inhibitors: disrupting bacterial communication for Next-Gen therapies

The rise of antibiotic-resistant bacteria and biofilm-related infections presents a significant challenge in modern medicine, necessitating the development of novel therapeutic strategies. Lactones, compounds that can mimic N-acyl homoserine lactones (AHLs), have the potential to disrupt quorum sensing (QS) in pathogenic biofilm-forming bacteria. In this study, we evaluated the antibacterial and antibiofilm properties of five different lactones-γ-caprolactone, γ-decalactone, δ-decalactone, γ-octalactone, and γ-methyl decalactone-along with a lab-produced lactone from newly isolated strains, against Pseudomonas aeruginosa and Staphylococcus aureus. The bacterial growth was measured at 590 nm, and biofilm formation was quantified using the crystal violet staining method. The results showed that all lactones, except γ-methyl decalactone, significantly inhibited bacterial growth and reduced biofilm formation. δ-decalactone exhibited the highest antibacterial activity, with a 74.3% followed by γ-Caprolactone 66.8% inhibition, followed by lab produced mixture of lactone (Lx) with (64%) and γ-octalactone (61.7%) at 600 µg/mL. In terms of antibiofilm activity, lab produced mixture of lactone (Lx) achieved highest inhibition 58% eradication, outpacing γ-decalactone (53.1%) and γ-octalactone (50.8%) at 600 µg/mL. These findings underscore the potential of lactones, particularly δ-decalactone and laboratory produced mixture of lactones Lx, as effective quorum sensing disruptors and biofilm inhibitors. This strategy, utilizing naturally occurring lactones, provides a promising alternative for combating biofilm-related infections, which present a growing threat to public health. These compounds offer a novel approach for the development of therapies targeting bacterial communication pathways and biofilm formation.