Farnesol potentiates photodynamic inactivation of Staphylococcus aureus with the use of red light-activated porphyrin TMPyP.

Photodynamic inactivation (PDI) or antibacterial photodynamic therapy (aPDT) is a method based on the use of a photosensitizer, light of a proper wavelength and oxygen, which combined together leads to an oxidative stress and killing of target cells. PDI can be applied towards various pathogenic bacteria independently on their antibiotic resistance profile. Optimization of photodynamic treatment to eradicate the widest range of human pathogens remains challenging despite the availability of numerous photosensitizing compounds. Therefore, a search for molecules that could act as adjuvants potentiating antibacterial photoinactivation is of high scientific and clinical importance. Here we propose farnesol (FRN), a well described sesquiterpene, as a potent adjuvant of PDI, which specifically sensitizes Staphylococcus aureus to 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin tetratosylate (TMPyP) upon red light irradiation. Interestingly, the observed potentiation strongly depends on the presence of light. Analysis of this combined action of FRN and TMPyP, however, showed no influence of farnesol on TMPyP photochemical properties, i.e. the amount of reactive oxygen species that were produced by TMPyP in the presence of FRN. The accumulation rate of TMPyP in Staphylococcus aureus cells did not change, as well as the influence of staphyloxanthin inhibition. The precise mechanism of observed sensitization is unclear and probably involves specific molecular targets.