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PNAS:揭开新生隐球菌自我保护机制

来源:科技日报 2009-02-08 01:07

美国耶什华大学阿尔伯特爱因斯坦医学院的研究人员称,他们发现了新生隐球菌如何躲过人类免疫系统并导致疾病的过程,该发现有助于开发针对新生隐球菌感染的疫苗。相关研究报告发表在近期出版的美国《国家科学院院刊》(PNAS)上。

该研究负责人苏珊娜·佛瑞丝瓦哈尔表示,这些真菌最易感染免疫系统受损的患者,特别是艾滋病患者和因器官移植而必须采取终身免疫抑制治疗的患者。据估计,全球每年因真菌感染导致的死亡人数高达100万,而其中撒哈拉以南地区就有近60万。

新生隐球菌首先通过肺部感染侵入人体,而后蔓延至包括大脑在内的其他各处器官,被称为隐球菌病,可导致胸痛、干咳、腹部肿胀、头痛、视力模糊等症状。如未及时得到抗真菌药物的治疗,隐球菌病可以致命。

研究人员发现,新生隐球菌外表有一层类似胶囊一样的薄膜在其感染人体过程中起着重要的作用。当真菌进入人体后,其外膜便开始增大。当真菌的外膜增大到一定程度,人体免疫系统中负责清除病毒的巨噬细胞便无法将其吞噬。但研究人员现在还没有理解导致真菌外膜增大的机制。

经过分析,研究人员发现新生隐球菌保护外膜的主要成分是多聚糖,有较长的糖分子链。佛瑞丝瓦哈尔和同事通过利用一种被称为动态散射的技术发现,真菌外膜会将越来越多的糖类聚集在外膜的边缘,从而形成巨大的分子,使外膜沿着轴线向外扩张。

该发现将为药物介入治疗开创新的研究方向,并将为基础多聚糖生物学开创新的研究领域。目前人们对多聚糖还理解甚少,科学家们之前认为多聚糖只是简单增长到一个特定长度,并没有什么研究价值,但这项新研究暗示多聚糖中似乎存在一套人们还不知晓的复杂机制。(生物谷Bioon.com)

生物谷推荐原始出处:

PNAS,doi: 10.1073/pnas.0808995106,Susana Frases, Arturo Casadevall

Capsule of Cryptococcus neoformans grows by enlargement of polysaccharide molecules

Susana Frasesa, Bruno Pontesb, Leonardo Nimrichterc, Nathan B. Vianabd, Marcio L. Rodriguesc and Arturo Casadevallae1

aDepartment of Microbiology and Immunology and
eDivision of Infectious Diseases of the Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461;
bLaboratório de Pin?as óticas-Coordena??o de Programas de Estudos Avan?ados, Instituto de Ciências Biomédicas, and
cLaboratório de Estudos Integrados em Bioquímica Microbiana, Instituto de Microbiologia Professor Paulo de Góes,Universidade Federal do Rio de Janeiro, 21941-902, Rio de Janeiro, Brazil; and
dInstituto de Física, Universidade Federal do Rio de Janeiro, 21941-972, Rio de Janeiro, Brazil

Abstract

The human pathogenic fungus Cryptococcus neoformans has a distinctive polysaccharide (PS) capsule that enlarges during infection. The capsule is essential for virulence, but the mechanism for capsular growth is unknown. In the present study, we used dynamic light scattering (LS) analysis of capsular PS and optical tweezers (OT) to explore the architecture of the capsule. Analysis of capsular PS from cells with small and large capsules by dynamic LS revealed a linear correlation between PS effective diameter and microscopic capsular diameter. This result implied that capsule growth was achieved by the addition of molecules with larger effective diameter, such that some molecules can span the entire diameter of the capsule. Measurement of polystyrene bead penetration of C. neoformans capsules by using OT techniques revealed that the outer regions were penetrable, but not the inner regions. Our results provide a mechanism for capsular enlargement based on the axial lengthening of PS molecules and suggest a model for the architecture of a eukaryotic microbial capsule.

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