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-<i>γ</i>-caprolactone, <i>γ</i>-decalactone, <i>δ</i>-decalactone, <i>γ</i>-octalactone, and <i>γ</i>-methyl decalactone-along with a lab-produced lactone from newly isolated strains, against <i>Pseudomonas aeruginosa</i> and <i>Staphylococcus aureus</i>. 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 <i>γ</i>-methyl decalactone, significantly inhibited bacterial growth and reduced biofilm formation. <i>δ</i>-decalactone exhibited the highest antibacterial activity, with a 74.3% followed by <i>γ</i>-Caprolactone 66.8% inhibition, followed by lab produced mixture of lactone (Lx) with (64%) and <i>γ</i>-octalactone (61.7%) at 600 µg/mL. In terms of antibiofilm activity, lab produced mixture of lactone (Lx) achieved highest inhibition 58% eradication, outpacing <i>γ</i>-decalactone (53.1%) and <i>γ</i>-octalactone (50.8%) at 600 µg/mL. These findings underscore the potential of lactones, particularly <i>δ</i>-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.