Repurposing Farnesol for Combating Drug-Resistant and Persistent Single and Polymicrobial Biofilms

Abstract

Biofilm-associated infections caused by drug-resistant and persistent bacteria remain a significant clinical challenge. Here we report that farnesol, commercially available as a cosmetic and flavoring agent, shows significant anti-biofilm properties when dissolved in ethanol using a proprietary formulation emulsion technique. Farnesol in the new formulation inhibits biofilm formation and disrupts established biofilms for Gram-positive <i>Staphylococcus aureus</i> and Gram-negative <i>Pseudomonas aeruginosa</i>, including their polymicrobial biofilms, and, moreover, kills <i>S. aureus</i> persister cells that have developed tolerance to antibiotics. No resistance to farnesol was observed for <i>S. aureus</i> after twenty continuous passages. Farnesol combats biofilms by direct killing, while also facilitating biofilm detachment. Furthermore, farnesol was safe and effective for preventing and treating biofilm-associated infections of both types of bacteria in an ex vivo burned human skin model. These data suggest that farnesol in the new formulation is an effective broad-spectrum anti-biofilm agent with promising clinical potential. Due to its established safety, low-cost, versatility, and excellent efficacy-including ability to reduce persistent and resistant microbial populations-farnesol in the proprietary formulation represents a compelling transformative, translational, and commercial platform for addressing many unsolved clinical challenges.