1] Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark. [2] Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.
1] Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark. [2] Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark.
Nat Genet. 2015 Jan;47(1):57-64. doi: 10.1038/ng.3148. Epub 2014 Nov 17.
Little is known about how within-host evolution compares between genotypically different strains of the same pathogenic species. We sequenced the whole genomes of 474 longitudinally collected clinical isolates of Pseudomonas aeruginosa sampled from 34 children and young individuals with cystic fibrosis. Our analysis of 36 P. aeruginosa lineages identified convergent molecular evolution in 52 genes. This list of genes suggests a role in host adaptation for remodeling of regulatory networks and central metabolism, acquisition of antibiotic resistance and loss of extracellular virulence factors. Furthermore, we find an ordered succession of mutations in key regulatory networks. Accordingly, mutations in downstream transcriptional regulators were contingent upon mutations in upstream regulators, suggesting that remodeling of regulatory networks might be important in adaptation. The characterization of genes involved in host adaptation may help in predicting bacterial evolution in patients with cystic fibrosis and in the design of future intervention strategies.
关于同一病原种的不同基因型菌株在宿主内的进化有何不同，目前知之甚少。我们对从 34 名患有囊性纤维化的儿童和年轻个体中采集的 474 株纵向收集的铜绿假单胞菌临床分离株进行了全基因组测序。我们对 36 个铜绿假单胞菌谱系的分析确定了 52 个基因的趋同分子进化。这组基因表明，在宿主适应过程中，调控网络和中心代谢的重塑、抗生素耐药性的获得和细胞外毒力因子的丧失可能发挥了作用。此外，我们发现关键调控网络中的突变存在有序的连续顺序。因此，下游转录调控因子的突变取决于上游调控因子的突变，这表明调控网络的重塑可能在适应中很重要。参与宿主适应的基因的特征可能有助于预测囊性纤维化患者中细菌的进化，并为未来的干预策略设计提供帮助。
