Antibiofilm and resistance-modulating properties of tt-farnesol against Streptococcus equi subsp. equi and zooepidemicus.

The aim of this study was to investigate the antibacterial, antibiofilm and modulating activities of trans-trans-farnesol (tt-farnesol) on two strains of Streptococcus equi subsp. equi and two strains of S. equi subsp. zooepidemicus, pathogenic or commensal bacteria of horses. Tt-farnesol showed bactericidal activity against all tested strains, with a minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) between 8 and 4 μg/mL. The sesquiterpene caused significant damage to the bacterial membrane, and its antibacterial activity did not appear to depend on oxidative stress induction. In addition to inhibiting planktonic bacteria, tt-farnesol inhibited biofilm formation, reducing biomass by up to 58.9% at 1 μg/mL. Furthermore, subinhibitory concentrations (1 μg/mL and 0.5 μg/mL) also synergistically modulated tetracycline resistance in the strains, restoring antibiotic sensitivity. The rhodamine 6G assay suggested modulation of efflux pumps and, in silico evaluations indicated affinity of tt-farnesol for the proteins 1YUB (methylase), 6PON (involved in biofilm formation), and 3OP1 (efflux pump). Considering the importance of these strains for equine health, with a direct impact on the economy, this is the first study to demonstrate therapeutic potential of tt-farnesol as an antibacterial agent and modulator against resistant strains of S. equi.