科學(xué)家發(fā)現(xiàn)了他們認為是讓一種新發(fā)真菌菌株進化并導(dǎo)致自1999年起溫哥華島的幾例死亡的原因,。這項發(fā)現(xiàn)可能有助于科學(xué)家理解為什么這種導(dǎo)致了全世界非常少的感染病例的真菌在西北太平洋地區(qū)變得致命,。
Robin May及其同事發(fā)現(xiàn),,隱球菌(Cryptococcus gattii)溫哥華島暴發(fā)菌株顯著增加了其在一種稱為巨噬細胞的免疫細胞內(nèi)部的繁殖能力,。巨噬細胞通常幫助抵御寄生蟲,。這種真菌在巨噬細胞內(nèi)部的繁殖削弱了宿主抵御感染和啟動合適的免疫應(yīng)答的能力,,這解釋了為什么健康人在這場暴發(fā)中死亡或者生病,。盡管許多病原體試圖在細胞內(nèi)躲避免疫系統(tǒng),,并利用宿主細胞的能源供應(yīng)和原材料,,這組作者發(fā)現(xiàn)了溫哥華島暴發(fā)菌株上調(diào)了一大組基因的表達,這些基因或者在該菌株的制造能量的線粒體內(nèi)部,,或者與其有關(guān),。線粒體改變了狀態(tài),這有助于這種真菌在巨噬細菌的消化細胞器內(nèi)部的破壞性環(huán)境中生存,。這組作者說,,線粒體產(chǎn)生的這種變化可能是其他病原體采用的一種策略。(生物谷Bioon.com)
生物谷推薦原始出處:
PNAS doi: 10.1073/pnas.0902963106
The fatal fungal outbreak on Vancouver Island is characterized by enhanced intracellular parasitism driven by mitochondrial regulation
Hansong Maa, Ferry Hagenb,c, Dov J. Stekela, Simon A. Johnstona, Edward Sionovd, Rama Falkd, Itzhack Polacheckd, Teun Boekhoutb,c and Robin C. Maya,1
In 1999, the population of Vancouver Island, Canada, began to experience an outbreak of a fatal fungal disease caused by a highly virulent lineage of Cryptococcus gattii. This organism has recently spread to the Canadian mainland and Pacific Northwest, but the molecular cause of the outbreak remains unknown. Here we show that the Vancouver Island outbreak (VIO) isolates have dramatically increased their ability to replicate within macrophages of the mammalian immune system in comparison with other C. gattii strains. We further demonstrate that such enhanced intracellular parasitism is directly linked to virulence in a murine model of cryptococcosis, suggesting that this phenotype may be the cause of the outbreak. Finally, microarray studies on 24 C. gattii strains reveals that the hypervirulence of the VIO isolates is characterized by the up-regulation of a large group of genes, many of which are encoded by mitochondrial genome or associated with mitochondrial activities. This expression profile correlates with an unusual mitochondrial morphology exhibited by the VIO strains after phagocytosis. Our data thus demonstrate that the intracellular parasitism of macrophages is a key driver of a human disease outbreak, a finding that has significant implications for a wide range of other human pathogens.