The limitation of our current arsenal of effective antibiotics, together with the lack of new antibacterial alternatives, is accelerating the onset of a “post-antibiotic era” that threatens many achievements of modern medicine. Recycling existing antibiotics represents a promising strategy to address the antimicrobial resistance crisis. In particular, combining antibiotics with non-antibiotic molecules that target specific resistance mechanisms may be more effective than the discovery of entirely new drugs. Natural products, especially phytochemicals derived from plant secondary metabolism, display antimicrobial activity and are therefore of significant interest for antimicrobial therapy.
In this study, a panel of 50 phytochemical products from different chemical classes (alkaloids, glucosinolate hydrolysis products, phenolics, and terpenes) was evaluated for antimicrobial activity and antibiotic potentiation against Pseudomonas aeruginosa and Staphylococcus aureus. Modes of action were investigated by assessing interference with key physiological processes, including motility, extracellular enzyme production, quorum sensing, membrane integrity, and intracellular content release, in order to clarify the mechanisms underlying antibiotic potentiation. Phytochemicals were also assessed for biofilm control, examining effects on bacterial viability and biofilm structure.
Not all phytochemicals exhibited antimicrobial or antibiotic-potentiating activity. Among the most active compounds, furvina showed strong antimicrobial effects against both P. aeruginosa and S. aureus by disrupting bacterial membranes and inducing intracellular content release. Furvina also potentiated antibiotic activity and inhibited the quorum sensing system of P. aeruginosa and related phenotypes, although it showed no activity against the Agr quorum sensing system of S. aureus. Phytochemicals that interfered with quorum sensing significantly impaired biofilm formation but had limited effects on established biofilms, particularly regarding biofilm dispersal.
In conclusion, phytochemicals can complement antibiotic activity and effectively prevent biofilm formation, although they are unable to induce dispersal of mature biofilms. This approach supports future Nature-based strategies targeting resistance without increasing selective pressure.
