Department of Biology, Centre for Advanced Research in Environmental Genomics, and Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada K1N 6N5.
Proc Natl Acad Sci U S A. 2013 Dec 24;110(52):21065-70. doi: 10.1073/pnas.1307862110. Epub 2013 Dec 9.
Pseudomonas aeruginosa is an opportunistic pathogen of humans and is a major cause of morbidity and mortality in patients with cystic fibrosis (CF). Prolonged infection of the respiratory tract can lead to adaptation of the pathogen to the CF lung environment. To examine the general patterns of adaptation associated with chronic infection, we obtained genome sequences from a collection of P. aeruginosa isolated from airways of patients with CF. Our analyses support a nonclonal epidemic population structure, with a background of unique, recombining genotypes, and the rare occurrence of successful epidemic clones. We present unique genome sequence evidence for the intercontinental spread of an epidemic strain shared between CF clinics in the United Kingdom and North America. Analyses of core and accessory genomes identified candidate genes and important functional pathways associated with adaptive evolution. Many genes of interest were involved in biological functions with obvious roles in this pathosystem, such as biofilm formation, antibiotic metabolism, pathogenesis, transport, reduction/oxidation, and secretion. Key factors driving the adaptive evolution of this pathogen within the host appear to be the presence of oxidative stressors and antibiotics. Regions of the accessory genome unique to the epidemic strain were enriched for genes in transporter families that efflux heavy metals and antibiotics. The epidemic strain was significantly more resistant than nonepidemic strains to three different antibiotics. Multiple lines of evidence suggest that selection imposed by the CF lung environment has a major influence on genomic evolution and the genetic characteristics of P. aeruginosa isolates causing contemporary infection.
铜绿假单胞菌是人类的机会性病原体，是囊性纤维化 (CF) 患者发病率和死亡率的主要原因。呼吸道的长期感染可导致病原体适应 CF 肺部环境。为了研究与慢性感染相关的一般适应模式，我们从 CF 患者气道中分离的铜绿假单胞菌收集获得了基因组序列。我们的分析支持非克隆流行人群结构，具有独特的、重组基因型背景，以及成功的流行克隆的罕见发生。我们提供了独特的基因组序列证据，证明了一种在英国和北美的 CF 诊所之间共享的流行菌株的洲际传播。核心和辅助基因组的分析确定了与适应性进化相关的候选基因和重要功能途径。许多感兴趣的基因参与了与这个病理系统明显相关的生物学功能，如生物膜形成、抗生素代谢、发病机制、运输、还原/氧化和分泌。在宿主内驱动这种病原体适应性进化的关键因素似乎是氧化应激和抗生素的存在。流行菌株特有的辅助基因组区域富含外排重金属和抗生素的转运蛋白家族基因。与非流行株相比，流行株对三种不同的抗生素的耐药性显著更高。多种证据表明，CF 肺部环境施加的选择对基因组进化和引起当代感染的铜绿假单胞菌分离株的遗传特征有重大影响。
