美國(guó)耶什華大學(xué)阿爾伯特愛(ài)因斯坦醫(yī)學(xué)院的研究人員稱(chēng),，他們發(fā)現(xiàn)了新生隱球菌如何躲過(guò)人類(lèi)免疫系統(tǒng)并導(dǎo)致疾病的過(guò)程,，該發(fā)現(xiàn)有助于開(kāi)發(fā)針對(duì)新生隱球菌感染的疫苗。相關(guān)研究報(bào)告發(fā)表在近期出版的美國(guó)《國(guó)家科學(xué)院院刊》（PNAS）上,。
該研究負(fù)責(zé)人蘇珊娜·佛瑞絲瓦哈爾表示,，這些真菌最易感染免疫系統(tǒng)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(jù)估計(jì),，全球每年因真菌感染導(dǎo)致的死亡人數(shù)高達(dá)100萬(wàn)，而其中撒哈拉以南地區(qū)就有近60萬(wàn),。
新生隱球菌首先通過(guò)肺部感染侵入人體,，而后蔓延至包括大腦在內(nèi)的其他各處器官，被稱(chēng)為隱球菌病,，可導(dǎo)致胸痛,、干咳、腹部腫脹,、頭痛,、視力模糊等癥狀。如未及時(shí)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(xiàn)，新生隱球菌外表有一層類(lèi)似膠囊一樣的薄膜在其感染人體過(guò)程中起著重要的作用,。當(dāng)真菌進(jìn)入人體后,，其外膜便開(kāi)始增大。當(dāng)真菌的外膜增大到一定程度,，人體免疫系統(tǒng)中負(fù)責(zé)清除病毒的巨噬細(xì)胞便無(wú)法將其吞噬,。但研究人員現(xiàn)在還沒(méi)有理解導(dǎo)致真菌外膜增大的機(jī)制,。
經(jīng)過(guò)分析，研究人員發(fā)現(xiàn)新生隱球菌保護(hù)外膜的主要成分是多聚糖,，有較長(zhǎng)的糖分子鏈,。佛瑞絲瓦哈爾和同事通過(guò)利用一種被稱(chēng)為動(dòng)態(tài)散射的技術(shù)發(fā)現(xiàn)，真菌外膜會(huì)將越來(lái)越多的糖類(lèi)聚集在外膜的邊緣,，從而形成巨大的分子,，使外膜沿著軸線(xiàn)向外擴(kuò)張。
該發(fā)現(xiàn)將為藥物介入治療開(kāi)創(chuàng)新的研究方向,，并將為基礎(chǔ)多聚糖生物學(xué)開(kāi)創(chuàng)新的研究領(lǐng)域,。目前人們對(duì)多聚糖還理解甚少，科學(xué)家們之前認(rèn)為多聚糖只是簡(jiǎn)單增長(zhǎng)到一個(gè)特定長(zhǎng)度,，并沒(méi)有什么研究?jī)r(jià)值,，但這項(xiàng)新研究暗示多聚糖中似乎存在一套人們還不知曉的復(fù)雜機(jī)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.
