In vitro photodynamic inactivation effects of benzylidene cyclopentanone photosensitizers on clinical fluconazole-resistant Candida albicans

Publication date: Available online 4 April 2018
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Shaona Zhou, Zhiyuan Sun, Zulin Ye, Ying Wang, Leili Wang, Limei Xing, Haixia Qiu, Naiyan Huang, Yanping Luo, Yuxia Zhao, Ying Gu
BackgroundThe incidence of Candida infections has increased for various reasons, for instance, the more frequent use of immunosuppresants or broad-spectrum antibiotics. Photodynamic inactivation (PDI) is a promising approach for treating localized Candida infections.MethodsThe PDI efficacies of three benzylidene cyclopentanone-based (BCB) photosensitizers (PSs: P1, P2 and Y1) against three fluconazole-resistant C. albicans (cal-1, cal-2, and cal-3) and one control C. albicans (ATCC 90028), respectively, were evaluated using an established plate dilution method. The binding of PSs to C. albicans was determined by fluorescence spectroscopy. The mechanism of antifungal PDI was investigated using confocal laser scanning microscopy (CLSM) and transmission electron microscopy (TEM).ResultsThree BCB PSs all bound rapidly to C. albicans. After incubation with PSs for 30 min and irradiation with a 532 nm laser for 10 min (40 mW cm^-2, 24 J cm^-2), the fungicidal activity was achieved as 7.5 µM for P1 and P2, and 25 µM for Y1. CLSM confirmed that P1 and Y1 were located in intracellular components, including mitochondria, while P2 bound to the protoplast exterior and failed to enter the cells. TEM revealed the damage of mitochondria ultrastructures after P1- or Y1-mediated PDI, consistenting with the CLSM results. However, most cells became edematous, enlarged or deformation after P2-mediated PDI.ConclusionsThe three BCB PSs all have remarkable PDI effects on C. albicans. The best effect is obtained by P1, which has one cationic charge with a proper lipophilicity. The respective subcellular localization of the three PSs led to different PDI mechanisms.



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