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Synthesis of Melanin-Like Pigments by Sporothrix schenckii In Vitro and during Mammalian Infection

机译:Sporothrix schenckii的体外合成和哺乳动物感染过程中类似黑色素的色素的合成

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Melanin has been implicated in the pathogenesis of several important human fungal pathogens. Existing data suggest that the conidia of the dimorphic fungal pathogen Sporothrix schenckii produce melanin or melanin-like compounds; in this study we aimed to confirm this suggestion and to demonstrate in vitro and in vivo production of melanin by yeast cells. S. schenckii grown on Mycosel agar produced visibly pigmented conidia, although yeast cells grown in brain heart infusion and minimal medium broth appeared to be nonpigmented macroscopically. However, treatment of both conidia and yeast cells with proteolytic enzymes, denaturant, and concentrated hot acid yielded dark particles similar in shape and size to the corresponding propagules, which were stable free radicals consistent with identification as melanins. Melanin particles extracted from S. schenckii yeast cells were used to produce a panel of murine monoclonal antibodies (MAbs) which labeled pigmented conidia, yeast cells, and the isolated particles. Tissue from hamster testicles infected with S. schenckii contained fungal cells that were labeled by melanin-binding MAbs, and digestion of infected hamster tissue yielded dark particles that were also reactive. Additionally, sera from humans with sporotrichosis contained antibodies that bound melanin particles. These findings indicate that S. schenckii conidia and yeast cells can produce melanin or melanin-like compounds in vitro and that yeast cells can synthesize pigment in vivo. Since melanin is an important virulence factor in other pathogenic fungi, this pigment may have a similar role in the pathogenesis of sporotrichosis.
机译:黑色素与几种重要的人类真菌病原体的发病机理有关。现有数据表明,双形真菌病原菌 Sporothrix schenckii 的分生孢子产生黑色素或类黑色素化合物。在这项研究中,我们旨在证实这一建议并证明酵母细胞在体内和体外产生黑色素。 S。尽管在脑心浸液中生长的酵母细胞和最低限度的培养基肉汤在宏观上看来没有色素沉着,但在Mycosel琼脂上生长的schenckii产生了明显的色素分生孢子。但是,用蛋白水解酶,变性剂和浓热酸处理分生孢子和酵母细胞均会产生深色颗粒,其形状和大小与相应的繁殖体相似,它们是稳定的自由基,与黑色素相鉴别。从 S中提取的黑色素颗粒。 schenckii酵母细胞用于产生一组鼠单克隆抗体(MAb),这些抗体标记有色分生孢子,酵母细胞和分离的颗粒。感染了 S的仓鼠睾丸组织。 schenckii 含有被黑色素结合的单克隆抗体标记的真菌细胞,被感染的仓鼠组织的消化产生了黑色颗粒,它们也具有反应性。此外,患有孢子体增生症的人的血清中含有结合黑色素颗粒的抗体。这些发现表明 S。 schenckii分生孢子和酵母细胞可在体外产生黑色素或类黑色素化合物,而酵母细胞可在体内合成色素。由于黑色素是其他致病真菌中的重要毒力因子,因此这种色素可能在孢子体增生病的发病机理中具有相似的作用。

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