Pseudomonas aeruginosa Population Diversity and Turnover in Cystic Fibrosis Chronic Infections
Pseudomonas aeruginosa Population Diversity and Turnover in Cystic Fibrosis Chronic Infections
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DOI：
10.1164/rccm.201009-1430oc
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发表时间：
2011-06-15
影响因子：
24.7
通讯作者：
Winstanley, Craig
中科院分区：
文献类型：
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作者：
Mowat, Eilidh;Paterson, Steve;Winstanley, Craig
理由：从慢性囊性纤维化肺部感染中分离出来的铜绿假单胞菌表现出多种表型，表明存在广泛的种群多样性。目的：我们旨在研究这种多样性在患者体内和患者之间的分布情况，并研究多个患者中单菌株表型多样性随时间变化的动态。方法：对每个痰样本的 40 个铜绿假单胞菌分离株进行了分析 系列的表型和基因型特征。分析了患者之间、患者样本之间以及样本内分离株之间的群体分化。测量和主要结果：我们对 2009 年期间对 10 名囊性纤维化慢性感染患者进行多重采样的重要且广泛传播的铜绿假单胞菌流行菌株总共 1,720 个分离株的 15 个特征进行了分析。总体而言，分析了 43 个痰样本和 398 个单倍型。 利物浦发现流行毒株。大多数表型多样性发生在患者体内。这种多样性是高度动态的，显示出单倍型随时间的快速更替。每个痰样本中的铜绿假单胞菌种群都具有广泛的多样性。尽管我们观察到每隔几个月采集的样本之间患者体内单倍型组成发生了重大变化，但在恶化期间，尽管使用了静脉注射抗生素，但组成的变化要小得多。我们的数据还强调了肺部病情恶化时期与绿脓菌素（一种群体感应控制的毒力因子）过量产生之间的相关性。结论：这些结果显着增进了我们对囊性纤维化患者感染期间铜绿假单胞菌在宿主群体内生物学的理解，并为绿脓菌素产生与患者发病率之间的联系提供了体内证据。
Rationale: Pseudomonas aeruginosa isolates from chronic cystic fibrosis lung infections display multiple phenotypes indicating extensive population diversity.Objectives: We aimed to examine how such diversity is distributed within and between patients, and to study the dynamics of single-strain phenotypic diversity in multiple patients through time.Methods: Sets of 40 P. aeruginosa isolates per sputum samples were analyzed for a series of phenotypic and genotypic characteristics. Population differentiation between patients, between samples within patients, and between isolates within samples was analyzed.Measurements and Main Results: We characterized 15 traits for a total of 1,720 isolates of an important and widely disseminated epidemic strain of P. aeruginosa from 10 chronically infected patients with cystic fibrosis multiply sampled during 2009. Overall, 43 sputum samples were analyzed and 398 haplotypes of the Liverpool Epidemic Strain were identified. The majority of phenotypic diversity occurred within patients. Such diversity is highly dynamic, displaying rapid turnover of haplotypes through time. P. aeruginosa populations within each individual sputum sample harbored extensive diversity. Although we observed major changes in the haplotype composition within patients between samples taken at intervals of several months, the compositions varied much less during exacerbation periods, despite the use of intravenous antibiotics. Our data also highlight a correlation between periods of pulmonary exacerbation and the overproduction of pyocyanin, a quorum sensing-controlled virulence factor.Conclusions: These results significantly advance our understanding of the within-host population biology of P. aeruginosa during infection of patients with cystic fibrosis, and provide in vivo evidence for a link between pyocyanin production and patient morbidity.