Melanin biosynthesis in Madurella mycetomatis and its effect on susceptibility to itraconazole and ketoconazole
Melanin biosynthesis in Madurella mycetomatis and its effect on susceptibility to itraconazole and ketoconazole
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DOI：
10.1016/j.micinf.2007.05.015
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发表时间：
2007-07-01
影响因子：
5.8
通讯作者：
van Belkum, Alex
中科院分区：
文献类型：
--
作者：
van de Sande, Wendy W. J.;de Kat, Johan;van Belkum, Alex
真菌肿的特征之一是形成真菌颗粒，由感染组织中的多个鼻窦分泌。 Madurella mycetomatis 颗粒是黑色的。这种黑色被证明是由于黑色素的存在造成的。黑色素可以通过多种生化途径产生。看来，足菌分枝杆菌黑化可以被 pyo 和二羟基萘 (DHN) 黑色素途径抑制剂阻断，但不能被二羟基苯丙氨酸 (L-DOPA) 黑色素途径抑制剂阻断。从分枝杆菌细胞中分离出的黑色素可提供体外保护，抵抗氧化剂高锰酸盐和几种抗真菌剂的杀伤作用。当将黑色素添加到培养基中时，发现伊曲康唑的 MIC 升高了 16 倍，酮康唑的 MIC 升高了 32 倍。两性霉素 B、氟康唑和伏立康唑的 MIC 不受影响。由于伊曲康唑和酮康唑是用于治疗足菌肿的主要抗真菌药物，因此应进一步研究体外 MIC 升高的临床相关性。 (C) 2007 Elsevier Masson SAS。版权所有。
One of the hallmarks of eumycetoma is the formation of fungal grains, which are secreted by multiple sinuses in infected tissues. Madurella mycetomatis grains are black. This black colour was shown to be due to the presence of melanin. Melanin can be produced through various biochemical pathways. It appeared that M. mycetomatis melanisation could be blocked by inhibitors of the pyo- and dihydroxynaphthalene (DHN)-melanin pathways but not by inhibitors of the dihydroxyphenylalanine (L-DOPA)-melanin pathway. Melanin isolated from M. mycetomatis cells provides in vitro protection against the killing effects of the oxidant permanganate and several antifungals. When melanin was added to the culture medium, MICs were found to be 16-fold elevated in the case of itraconazole and 32-fold for ketoconazole. MICs for amphotericin B, fiuconazole and voriconazole were not affected. Since itraconazole and ketoconazole are the main antifungal agents used to treat mycetoma, the clinical relevance of the in vitro rise in MIC should be studied further. (C) 2007 Elsevier Masson SAS. All rights reserved.