Comparison of thiocyanate and selenocyanate for potentiation of antimicrobial photodynamic therapy

We have previously shown that antimicrobial photodynamic therapy (aPDT) mediated by different photosensitizers (PS) can be potentiated by a variety of inorganic salts. Potassium thiocyanate (KSCN) potentiated aPDT mediated by methylene blue (MB), while potassium selenocyanate (KSeCN) potentiated aPDT mediated by MB, Rose Bengal and the anionic porphyrin 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin dihydrochloride. However, the mechanisms of action that were proposed were fundamentally different. In the present study, we compare these two salts (KSCN and KSeCN) with different light-activated PS and different oxidative reactions for killing gram-positive and gram-negative bacteria. Overall KSeCN was more powerful than KSCN, and worked with a wider range of PS, while KSCN only worked with phenothiazinium salts. KSeCN produced killing when cells were added after light suggesting production of a semistable species called selenocyanogen (SeCN)₂. We tested three different oxidative reactions that can all potentially kill bacteria: lead tetraacetate (Pb[OAc]₄); Fenton reagent (hydrogen peroxide [H₂O₂] and ferrous sulfate) H₂O₂and horseradish peroxidase (HRP). In every case, KSeCN was substantially more effective (several logs) than KSCN in potentiating the bacterial killing. We conclude that (SeCN)₂ is the mediator for aPDT using KSeCN, while sulfur trioxide radical anion is the mediator for KSCN using phenothiaziums. For H₂O₂/HRP with KSCN, hypothiocyanite is proposed to be the antibacterial agent in the literature, while hyposelenocyanite is said not to exist. Pb[OAc]₄ is known to produce (SeCN)₂ from KSeCN as well as the analogous (SCN)₂ from KSCN. The mediators from Fenton reaction are unclear (pseudohalogen radical ions?) Both KSCN (which occurs naturally in the human body) and KSeCN may be clinically applicable.