Effects of Candida albicans-derived Farnesol and Tyrosol on Quorum-Sensing Pathways in Pseudomonas aeruginosa Biofilms: Implication for Antimicrobial Resistance

Abstract

In 2017, amid an antimicrobial crisis, the World Health Organization classified Pseudomonas Aeruginosa as a priority pathogen for the Research and Development of new antibiotics. P. aeruginosa’s ability to form biofilms–structured aggregation of microcolonies embedded in a self-generated matrix–and regulate virulence through quorum-sensing (QS) often results in antibiotic failure, especially in nosocomial settings. As synthetic antibiotics have become increasingly ineffective in eradicating P. aeruginosa biofilm, chronic infections persist in cystic fibrosis and burn wound patients. This review investigates C.albicans-derived molecules, tyrosol, and farnesol, as potential quorum-sensing inhibitors (QSIs) of P. aeruginosa QS circuits (LasI/LasR, RhlI/RhIR, and PQS) in single-species biofilms. These fungal-derived compounds have been shown to have anti-biofilm and antibacterial activity by disrupting P. aeruginosa QS pathways and modulating virulence factor expression. In combinatorial therapeutics, tyrosol and farnesol have been demonstrated to facilitate certain antibiotic activity, suggesting potential for clinical implementation. Unlike traditional antibiotics, C. albicans QSIs have co-evolved with P. aeruginosa and developed inhibition mechanisms that minimize the selective pressures driving antimicrobial resistance. By targeting cell-to-cell communication rather than bacterial growth, tyrosol and farnesol offer a propitious avenue for P. aeruginosa biofilms-associated infections. However, as this remains an emerging field of research in the context of P. aeruginosa-driven infections, further research is needed to determine clinical plausibility, especially in in-vivo models, to understand specific mechanisms of action, dosage optimization and potential undesirable off-target interactions.