近日,国际著名杂志《自然遗传学》Nature Genetics 在线刊登了研究人员的最新研究成果“Parallel bacterial evolution within multiple patients identifies candidate pathogenicity genes。”,文章中,研究者利用全基因组测序法,他们追踪了一种细菌病原体在洋葱伯克霍尔德菌(Burkholderia dolosa )在肺囊性纤维化患者中爆发的演化情况。
新研究为高通量测序技术在临床流行病设置的应用树立了一个榜样,也为研究致病菌在感染宿主期间其基因组的演化提供了新观点。洋葱伯克霍尔德菌在肺囊性纤维化患者中的爆发会导致肺炎。Roy Kishony和同事合作,追踪了20世纪90年代期间波士顿一家医院中洋葱伯克霍尔德菌感染爆发的历史。他们对采集自这次爆发中的14患者的洋葱伯克霍尔德菌进行了全基因组测序,其中有112个菌株是在16年的时间中分别采集的。他们实施了演化和流行病学的分析,并能推断病菌在这些患者中的传输网络。他们进一步鉴别出17个目标选择基因,认为它们在洋葱伯克霍尔德菌在人类宿主中的致病性和适应性的形成过程中发挥了作用。(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.