Antimicrobial photodynamic treatment (APDT) has emerged as an effective therapy against pathogenic fungi with both acquired and intrinsic resistance to commonly used antifungal agents. Success of APDT depends on the availability of effective photosensitizers capable of acting on different fungal structures and species. Among the phenothiazinium dyes tested as photoantifungals, new methylene blue N (NMBN) and the novel pentacyclic compound S137 are the most efficient. In the present study we compared the effects of APDT with NMBN and S137 on the survival of Candida albicans and employed a set of fluorescent probes (propidium iodide, FUN-1, JC-1, DHR-123 and DHE) together with confocal microscopy and flow cytometry to evaluate the effects of these two chemically diverse photosensitizers on cell membrane permeability, metabolism and redox status, and mitochondrial activity. Taken together, our results indicate that, due to chemical features resulting in different lipophilicity, NMBN and S137 localize to distinct subcellular structures and hence inactivate C. albicans cells via different mechanisms. S137 localizes mostly to the cell membrane and, upon light exposure, photo-oxidizes membrane lipids. NMBN readily localizes to mitochondria and exerts its photodynamic effects there, which was observed to be a less effective way to achieve cell death at lower light fluences.

抗菌光动力疗法（APDT）已成为一种有效的抗病原真菌的疗法，对常用的抗真菌药具有获得性和内在抗性。APDT的成功取决于能否对不同的真菌结构和物种起作用的有效光敏剂。在作为光抗真菌剂进行测试的吩噻嗪鎓染料中，新的亚甲基蓝N（NMBN）和新型的五环化合物S137是最有效的。在本研究中，我们比较了APDT与NMBN和S137对白色念珠菌存活的影响并使用了一套荧光探针（碘化丙啶，FUN-1，JC-1，DHR-123和DHE）以及共聚焦显微镜和流式细胞仪来评估这两种化学上不同的光敏剂对细胞膜通透性，代谢和氧化还原的影响状态和线粒体活动。两者合计，我们的结果表明，由于导致不同亲脂性的化学特征，NMBN和S137定位于不同的亚细胞结构，并因此通过不同的机制使白色念珠菌细胞失活。S137主要定位在细胞膜上，并且在曝光后会光氧化膜脂质。NMBN易于定位于线粒体并在其中发挥其光动力作用，据观察这是在较低光通量下实现细胞死亡的较不有效的方法。