Photodynamic inactivation of Candida albicans by a tetracationic tentacle porphyrin and its analogue without intrinsic charges in presence of fluconazole

Abstract

The photodynamic inactivation mediated by 5,10,15,20-tetrakis[4-(3-N,N-dimethylaminopropoxy)phenyl]porphyrin (TAPP) and 5,10,15,20-tetrakis[4-(3-N,N,N-trimethylaminepropoxy)phenyl]porphyrin (TAPP4+) were compared in Candida albicans cells. A strong binding affinity was found between these porphyrins and the yeast cells. Photosensitized inactivation of C. albicans increased with both photosensitizer concentration and irradiation time. After 30 min irradiation, a high photoinactivation (~5 log) was found for C. albicans treated with 5 μM porphyrin. Also, the photoinactivation of yeast cells was still elevated after two washing steps. However, the photocytotoxicity decreases with an increase in the cell density from 106 to 108 cells/mL. The high photodynamic activity of these porphyrins was also established by growth delay experiments. This C. albicans strain was susceptible to fluconazole with a MIC of 1.0 μg/mL. The effect of photosensitization and the action of fluconazole were combined to eradicate C. albicans. After a PDI treatment with 1 μM porphyrin and 30 min irradiation, the value of MIC decreased to 0.25 μg/mL. In addition, a complete arrest in cell growth was found by combining both effects. TAPP was similarly effective to photoinactivate C. albicans than TAPP4+. This porphyrin without intrinsic positive charges contains basic amino groups, which can be protonated at physiological pH. Moreover, an enhancement in the antifungal action was found using both therapies because lower doses of the agents were required to achieve cell death.