Calcofluor white combination antifungal treatments for Trichophyton rubrum and Candida albicans.
Calcofluor white combination antifungal treatments for Trichophyton rubrum and Candida albicans.
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DOI：
10.1371/journal.pone.0039405
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Pinnell SR
中科院分区：
文献类型：
--
作者：
Kingsbury JM;Heitman J;Pinnell SR
由皮肤真菌引起的浅部真菌病是世界上最常见的感染之一，但治疗受到有效药物有限、药物毒性和出现耐药性的限制。二苯乙烯类荧光增白剂钙氟白(CFW)通过与细胞壁中的甲壳素结合，破坏细胞壁的完整性来抑制真菌，因此需要一种不同于目前可用的抗真菌药物的抑制机制。为了确定治疗皮肤感染的新的治疗方案，我们比较了皮肤真菌红色毛霉菌和白色念珠菌的代表菌株对CFW和一组荧光增白剂和植物抗毒素化合物的敏感性。我们鉴定了结构上相关的二苯乙烯类荧光增白剂71、85、113和134对红色毛念珠菌和白色念珠菌的杀菌作用与CFW相似，二苯乙烯类植物抗菌素松香单甲醚和蕨类化合物对真菌的抑制程度较小，使我们能够建立抑制真菌的构效关系。考虑到CFW吸收UV365 nm并与真菌细胞壁特异结合的能力，我们测试了CFW与UV365 nm照射相结合是否对真菌具有协同作用，并提供了一种新的光动力学治疗选择。然而，虽然两种处理都具有细胞杀伤力，但UV365 nm照射降低了对CFW的敏感性，我们将其归因于CFW的光灭活。我们还测试了CFW与其他真菌抑制剂的联合治疗，并在白色念珠菌中确定了CFW与一些麦角固醇生物合成抑制剂之间的协同作用。因此，我们的研究确定了新的真菌抑制剂和药物相互作用，为浅部真菌病的联合局部治疗方案提供了希望。
Superficial mycoses caused by dermatophyte fungi are among the most common infections worldwide, yet treatment is restricted by limited effective drugs available, drug toxicity, and emergence of drug resistance. The stilbene fluorescent brightener calcofluor white (CFW) inhibits fungi by binding chitin in the cell wall, disrupting cell wall integrity, and thus entails a different mechanism of inhibition than currently available antifungal drugs. To identify novel therapeutic options for the treatment of skin infections, we compared the sensitivity of representative strains of the dermatophyte Trichophyton rubrum and Candida albicans to CFW and a panel of fluorescent brighteners and phytoalexin compounds. We identified the structurally related stilbene fluorescent brighteners 71, 85, 113 and 134 as fungicidal to both T. rubrum and C. albicans to a similar degree as CFW, and the stilbene phytoalexins pinosylvan monomethyl ether and pterostilbene inhibited to a lesser degree, allowing us to develop a structure-activity relationship for fungal inhibition. Given the abilities of CFW to absorb UV365 nm and bind specifically to fungal cell walls, we tested whether CFW combined with UV365 nm irradiation would be synergistic to fungi and provide a novel photodynamic treatment option. However, while both treatments individually were cytocidal, UV365 nm irradiation reduced sensitivity to CFW, which we attribute to CFW photoinactivation. We also tested combination treatments of CFW with other fungal inhibitors and identified synergistic interactions between CFW and some ergosterol biosynthesis inhibitors in C. albicans. Therefore, our studies identify novel fungal inhibitors and drug interactions, offering promise for combination topical treatment regimes for superficial mycoses.
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影响因子：
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