Melanin as a potential cryptococcal defence against microbicidal proteins
Melanin as a potential cryptococcal defence against microbicidal proteins
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DOI：
10.1046/j.1365-280x.1999.00218.x
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发表时间：
1999-06-01
期刊：
影响因子：
2.9
通讯作者：
Casadevall, A
中科院分区：
文献类型：
--
作者：
Doering, TL;Nosanchuk, JD;Casadevall, A
新型隐球菌是一种重要的真菌病原体，在酚类底物存在下生长时合成黑色素。C.黑色素的产生与新生儿的毒力有关，但黑色素在感染发病机制中的具体作用尚不清楚。本研究对C.研究了新生黑色素结合蛋白质和保护免受杀微生物肽的作用。黑色素被证明可以结合多种真菌和哺乳动物来源的蛋白质。黑色素-蛋白质相互作用取决于溶液的pH值和存在的蛋白质和黑色素的量。黑素化的细胞不太容易被三种杀微生物肽杀死：防御素、保护素和爪蟾抗菌肽。将杀微生物肽与黑色素颗粒一起孵育，然后除去黑色素，降低或消除了杀真菌活性，证明了肽与黑色素之间的相互作用。黑色素结合蛋白质和保护免受杀微生物肽的能力表明黑色素的保护功能，由此它螯合杀微生物肽并消除它们的活性。
Cryptococcus neoformans is an important fungal pathogen that synthesizes melanin when grown in the presence of phenolic substrates. The ability of C. neoformans to produce melanin is associated with virulence, but the specific role of melanin in the pathogenesis of infection is not clear. In this study the ability of C. neoformans melanin to bind proteins and protect against microbicidal peptides was investigated. Melanin was shown to bind a variety of proteins of fungal and mammalian origin. Melanin-protein interactions were dependent on the pH of the solution and on the amount of protein and melanin present. Melanized cells were less susceptible to killing by three microbicidal peptides: a defensin, a protegrin, and a magainin. Incubation of the microbicidal peptides with melanin particles, followed by removal of the melanin, reduced or abolished fungicidal activity, demonstrating interactions between peptides and melanin. The ability of melanin to bind proteins and to protect against microbicidal peptides suggests a protective function for melanin, whereby it sequesters microbicidal peptides and abrogates their activity.