美國耶什華大學阿爾伯特愛因斯坦醫(yī)學院的研究人員稱,,他們發(fā)現了新生隱球菌如何躲過人類免疫系統并導致疾病的過程,,該發(fā)現有助于開發(fā)針對新生隱球菌感染的疫苗。相關研究報告發(fā)表在近期出版的美國《國家科學院院刊》(PNAS)上,。
該研究負責人蘇珊娜·佛瑞絲瓦哈爾表示,,這些真菌最易感染免疫系統受損的患者,特別是艾滋病患者和因器官移植而必須采取終身免疫抑制治療的患者,。據估計,,全球每年因真菌感染導致的死亡人數高達100萬,而其中撒哈拉以南地區(qū)就有近60萬,。
新生隱球菌首先通過肺部感染侵入人體,,而后蔓延至包括大腦在內的其他各處器官,被稱為隱球菌病,,可導致胸痛,、干咳、腹部腫脹,、頭痛,、視力模糊等癥狀。如未及時得到抗真菌藥物的治療,,隱球菌病可以致命,。
研究人員發(fā)現,新生隱球菌外表有一層類似膠囊一樣的薄膜在其感染人體過程中起著重要的作用,。當真菌進入人體后,,其外膜便開始增大。當真菌的外膜增大到一定程度,,人體免疫系統中負責清除病毒的巨噬細胞便無法將其吞噬,。但研究人員現在還沒有理解導致真菌外膜增大的機制。
經過分析,,研究人員發(fā)現新生隱球菌保護外膜的主要成分是多聚糖,,有較長的糖分子鏈,。佛瑞絲瓦哈爾和同事通過利用一種被稱為動態(tài)散射的技術發(fā)現,真菌外膜會將越來越多的糖類聚集在外膜的邊緣,,從而形成巨大的分子,,使外膜沿著軸線向外擴張。
該發(fā)現將為藥物介入治療開創(chuàng)新的研究方向,,并將為基礎多聚糖生物學開創(chuàng)新的研究領域,。目前人們對多聚糖還理解甚少,科學家們之前認為多聚糖只是簡單增長到一個特定長度,,并沒有什么研究價值,,但這項新研究暗示多聚糖中似乎存在一套人們還不知曉的復雜機制。(生物谷Bioon.com)
生物谷推薦原始出處:
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.