Williams David, Evans Benjamin, Haldenby Sam, Walshaw Martin J, Brockhurst Michael A, Winstanley Craig, Paterson Steve
1 Institute of Integrative Biology and.
Am J Respir Crit Care Med. 2015 Apr 1;191(7):775-85. doi: 10.1164/rccm.201409-1646OC.
Pseudomonas aeruginosa, the predominant cause of chronic airway infections of patients with cystic fibrosis, exhibits extensive phenotypic diversity among isolates within and between sputum samples, but little is known about the underlying genetic diversity.
To characterize the population genetic structure of transmissible P. aeruginosa Liverpool Epidemic Strain in chronic infections of nine patients with cystic fibrosis, and infer evolutionary processes associated with adaptation to the cystic fibrosis lung.
We performed whole-genome sequencing of P. aeruginosa isolates and pooled populations and used comparative analyses of genome sequences including phylogenetic reconstructions and resolution of population structure from genome-wide allele frequencies.
Genome sequences were obtained for 360 isolates from nine patients. Phylogenetic reconstruction of the ancestry of 40 individually sequenced isolates from one patient sputum sample revealed the coexistence of two genetically diverged, recombining lineages exchanging potentially adaptive mutations. Analysis of population samples for eight additional patients indicated coexisting lineages in six cases. Reconstruction of the ancestry of individually sequenced isolates from all patients indicated smaller genetic distances between than within patients in most cases.
Our population-level analysis demonstrates that coexistence of distinct lineages of P. aeruginosa Liverpool Epidemic Strain within individuals is common. In several cases, coexisting lineages may have been present in the infecting inoculum or assembled through multiple transmissions. Divergent lineages can share mutations via homologous recombination, potentially aiding adaptation to the airway during chronic infection. The genetic diversity of this transmissible strain within infections, revealed by high-resolution genomics, has implications for patient segregation and therapeutic strategies.
铜绿假单胞菌是囊性纤维化患者慢性气道感染的主要病因，在痰液样本内和样本间的分离株中表现出广泛的表型多样性，但对其潜在的遗传多样性知之甚少。
描述9例囊性纤维化患者慢性感染中可传播的铜绿假单胞菌利物浦流行株的群体遗传结构，并推断与适应囊性纤维化肺部相关的进化过程。
我们对铜绿假单胞菌分离株和混合群体进行了全基因组测序，并使用了基因组序列的比较分析，包括系统发育重建和从全基因组等位基因频率解析群体结构。
获得了9例患者的360株分离株的基因组序列。对一名患者痰液样本中40株单独测序的分离株的祖先进行系统发育重建，发现两个遗传上不同的重组谱系共存，它们交换潜在的适应性突变。对另外8例患者的群体样本分析表明，6例存在共存谱系。对所有患者单独测序的分离株的祖先进行重建表明，在大多数情况下，患者之间的遗传距离小于患者内部的遗传距离。
我们的群体水平分析表明，个体内铜绿假单胞菌利物浦流行株不同谱系共存很常见。在一些情况下，共存谱系可能存在于感染接种物中，或通过多次传播聚集而成。不同的谱系可以通过同源重组共享突变，这可能有助于在慢性感染期间适应气道。高分辨率基因组学揭示的这种可传播菌株在感染中的遗传多样性，对患者隔离和治疗策略具有重要意义。
