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Biosynthesis and Functions of Melanin inSporothrix schenckii

机译:黑麦草中黑色素的生物合成与功能

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Sporothrix schenckii is a human pathogen that causes sporotrichosis, an important cutaneous mycosis with a worldwide distribution. It produces dark-brown conidia, which infect the host. We found that S. schenckii synthesizes melanin via the 1,8-dihydroxynaphthalene pentaketide pathway. Melanin biosynthesis in the wild type was inhibited by tricyclazole, and colonies of the fungus were reddish brown instead of black on tricyclazole-amended medium. Two melanin-deficient mutant strains were analyzed in this study: an albino that produced normal-appearing melanin on scytalone-amended medium and a reddish brown mutant that accumulated and extruded melanin metabolites into its medium. Scytalone and flaviolin obtained from cultures of the reddish brown mutant were identified by thin-layer chromatography, high-performance liquid chromatography, and UV spectra. Transmission electron microscopy showed an electron-dense granular material believed to be melanin in wild-type conidial cell walls, and this was absent in conidial walls of the albino mutant unless the albino was grown on a scytalone-amended medium. Melanized cells of wild-type S. schenckii and the albino grown on scytalone-amended medium were less susceptible to killing by chemically generated oxygen- and nitrogen-derived radicals and by UV light than were conidia of the mutant strains. Melanized conidia of the wild type and the scytalone-treated albino were also more resistant to phagocytosis and killing by human monocytes and murine macrophages than were unmelanized conidia of the two mutants. These results demonstrate that melanin protects S. schenckii against certain oxidative antimicrobial compounds and against attack by macrophages.
机译:sporothrix schenckii是一种人类病原体,可引起孢子虫病,一种重要的皮肤真菌病,在世界范围内分布。它产生深褐色的分生孢子,感染宿主。我们发现S. schenckii通过1,8-dihydroxynaphthalene pentaketide途径合成黑色素。三环唑抑制了野生型中黑色素的生物合成,并且在三环唑修饰的培养基上,真菌的菌落呈红棕色而不是黑色。在这项研究中,分析了两种黑色素缺陷型突变株:在白细胞介素修饰的培养基上产生正常出现的黑色素的白化病菌和将黑色素代谢物累积并挤出到其培养基中的红棕色突变株。通过薄层色谱法,高效液相色谱法和UV光谱鉴定了从红棕色突变体培养物中获得的半胱氨酸和黄酮。透射电子显微镜显示在野生型分生孢子细胞壁中被认为是黑色素的电子致密粒状物质,除非白化病在经鞘磷脂修饰的培养基上生长,否则在白化病突变体的分生孢子壁中不存在。与突变菌株的分生孢子相比,野生型S. schenckii和生长在长柄长柄改良培养基上的白化病的黑化细胞更不容易被化学生成的氧和氮衍生的自由基和紫外线杀死。与两个突变体的非黑色化分生孢子相比,野生型黑色化分生孢子和经大麦碱处理的白化病也对人类单核细胞和鼠巨噬细胞的吞噬作用和杀伤力具有更高的抵抗力。这些结果表明,黑色素保护申氏链球菌免受某些氧化性抗微生物化合物和巨噬细胞的侵袭。

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