Microstructure of cell wall-associated melanin in the human pathogenic fungus cryptococcus neoformans

Microstructure of cell wall-associated melanin in the human pathogenic fungus cryptococcus neoformans
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DOI:
10.1021/bi047731m
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发表时间:
2005-03-15
期刊:
影响因子:
2.9
通讯作者:
Casadevall, A
Casadevall, A
中科院分区:
生物学3区
文献类型:
--
作者:
Eisenman, HC;Nosanchuk, JD;Casadevall, A

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黑色素是许多致病性真菌物种的毒力因子,包括新型隐球菌。黑色素沉积在细胞壁上,从这种真菌中分离出来的黑色素保持了细胞的形状,形成了被称为“鬼”的中空球体。在本研究中,原子力、扫描电子和透射电子显微镜显示,黑色素幽灵被直径约为40-130 nm的大致球形颗粒颗粒覆盖,并且黑色素排列在多个同心层中。核磁共振冻孔测定显示,黑色素鬼影中除了少量直径在30 nm附近的孔隙外,还含有直径在1 ~ 4 nm之间的孔隙。抗体与黑色素的结合减少了这些毛孔的明显测量体积,这表明它们的抗真菌作用的机制。我们提出了隐球菌黑色素结构的模型,其中黑色素颗粒在层中保持在一起。这种结构模型对细胞分裂、细胞壁重塑和抗真菌药物的发现具有重要意义。
Melanin is a virulence factor for many pathogenic fungal species, including Cryptococcus neoformans. Melanin is deposited in the cell wall, and melanin isolated from this fungus retains the shape of the cells, resulting in hollow spheres called "ghosts". In this study, atomic force, scanning electron, and transmission electron microscopy revealed that melanin ghosts are covered with roughly spherical granular particles approximately 40-130 nm in diameter, and that the melanin is arranged in multiple concentric layers. Nuclear magnetic resonance cryoporometry indicated melanin ghosts contain pores with diameters between 1 and 4 nm, in addition to a small number of pores with diameters near 30 nm. Binding of the antibodies to melanin reduced the apparent measured volume of these pores, suggesting a mechanism for their antifungal effect. We propose a model of cryptococcal melanin structure whereby the melanin granules are held together in layers. This structural model has implications for cell division, cell wall remodeling, and antifungal drug discovery.