近日,，國(guó)際著名雜志《自然遺傳學(xué)》Nature Genetics 在線刊登了研究人員的最新研究成果“Parallel bacterial evolution within multiple patients identifies candidate pathogenicity genes。”,，文章中，研究者利用全基因組測(cè)序法,，他們追蹤了一種細(xì)菌病原體在洋蔥伯克霍爾德菌（Burkholderia dolosa ）在肺囊性纖維化患者中爆發(fā)的演化情況。
新研究為高通量測(cè)序技術(shù)在臨床流行病設(shè)置的應(yīng)用樹(shù)立了一個(gè)榜樣,，也為研究致病菌在感染宿主期間其基因組的演化提供了新觀點(diǎn),。洋蔥伯克霍爾德菌在肺囊性纖維化患者中的爆發(fā)會(huì)導(dǎo)致肺炎。Roy Kishony和同事合作,，追蹤了20世紀(jì)90年代期間波士頓一家醫(yī)院中洋蔥伯克霍爾德菌感染爆發(fā)的歷史,。他們對(duì)采集自這次爆發(fā)中的14患者的洋蔥伯克霍爾德菌進(jìn)行了全基因組測(cè)序，其中有112個(gè)菌株是在16年的時(shí)間中分別采集的,。他們實(shí)施了演化和流行病學(xué)的分析,，并能推斷病菌在這些患者中的傳輸網(wǎng)絡(luò)。他們進(jìn)一步鑒別出17個(gè)目標(biāo)選擇基因，認(rèn)為它們?cè)谘笫[伯克霍爾德菌在人類(lèi)宿主中的致病性和適應(yīng)性的形成過(guò)程中發(fā)揮了作用,。（生物谷Bioon.com）
doi:10.1038/ng.997
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Parallel bacterial evolution within multiple patients identifies candidate pathogenicity genes
Tami D Lieberman,Jean-Baptiste Michel,Mythili Aingaran,Gail Potter-Bynoe,Damien Roux,Michael R Davis Jr,David Skurnik,Nicholas Leiby,John J LiPuma,Joanna B Goldberg,Alexander J McAdam,Gregory P Priebe& Roy Kishony
Bacterial pathogens evolve during the infection of their human host, but separating adaptive and neutral mutations remains challenging9, 10, 11. Here we identify bacterial genes under adaptive evolution by tracking recurrent patterns of mutations in the same pathogenic strain during the infection of multiple individuals. We conducted a retrospective study of a Burkholderia dolosa outbreak among subjects with cystic fibrosis, sequencing the genomes of 112 isolates collected from 14 individuals over 16 years. We find that 17 bacterial genes acquired nonsynonymous mutations in multiple individuals, which indicates parallel adaptive evolution. Mutations in these genes affect important pathogenic phenotypes, including antibiotic resistance and bacterial membrane composition and implicate oxygen-dependent regulation as paramount in lung infections. Several genes have not previously been implicated in pathogenesis and may represent new therapeutic targets. The identification of parallel molecular evolution as a pathogen spreads among multiple individuals points to the key selection forces it experiences within human hosts.
