Parallel bacterial evolution within multiple patients identifies candidate pathogenicity genes.
Parallel bacterial evolution within multiple patients identifies candidate pathogenicity genes.
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作者：
细菌病原体在感染人类宿主的过程中进化，但分离适应性突变和中性突变仍然具有挑战性。在这里，我们通过跟踪多个患者感染过程中同一致病菌株的突变模式来识别适应性进化下的细菌基因。我们对囊性纤维化人群中的一次长痛伯克霍尔德菌爆发进行了回顾性研究，对16年来从14名个体中收集的112株分离株的基因组进行了测序。我们发现17个细菌基因在多个个体中获得非同义突变，这表明平行适应性进化。这些基因的突变阐明了重要致病表型的遗传基础，包括抗生素耐药性和细菌膜组成，并暗示氧依赖性基因调控在肺部感染中至关重要。一些基因以前没有参与发病机制，这表明新的治疗靶点。平行分子进化的确定表明了作用于人类病原体的关键选择力量，可以帮助预测和准备它们未来的进化过程。
Bacterial pathogens evolve during the infection of their human hosts, but separating adaptive and neutral mutations remains challenging. Here, we identify bacterial genes under adaptive evolution by tracking recurrent patterns of mutations in the same pathogenic strain during the infection of multiple patients. We conducted a retrospective study of a Burkholderia dolosa outbreak among people with cystic fibrosis, sequencing the genomes of 112 isolates collected from 14 individuals over 16 years. We find that 17 bacterial genes acquired non-synonymous mutations in multiple individuals, which indicates parallel adaptive evolution. Mutations in these genes illuminate the genetic basis of important pathogenic phenotypes, including antibiotic resistance and bacterial membrane composition, and implicate oxygen-dependent gene regulation as paramount in lung infections. Several genes have not been previously implicated in pathogenesis, suggesting new therapeutic targets. The identification of parallel molecular evolution suggests key selection forces acting on pathogens within humans and can help predict and prepare for their future evolutionary course.
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影响因子：
30.8
作者：
Holt, Kathryn E.;Parkhill, Julian;Mazzoni, Camila J.;Roumagnac, Philippe;Weill, Francois-Xavier;Goodhead, Ian;Rance, Richard;Baker, Stephen;Maskell, Duncan J.;Wain, John;Dolecek, Christiane;Achtman, Mark;Dougan, Gordon
通讯作者：
Dougan, Gordon
影响因子：
64.8
作者：
通讯作者：
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影响因子：
11
作者：
Guss, Adam M.;Roeselers, Guus;Cavanaugh, Colleen M.
通讯作者：
Cavanaugh, Colleen M.
DOI：
10.1164/rccm.201009-1430oc
发表时间：
2011-06-15
影响因子：
24.7
作者：
Mowat, Eilidh;Paterson, Steve;Winstanley, Craig
通讯作者：
Winstanley, Craig
影响因子：
64.8
作者：
通讯作者：
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