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铜绿假单胞菌在囊性纤维化慢性感染中的种群多样性和更替。

Pseudomonas aeruginosa population diversity and turnover in cystic fibrosis chronic infections.

机构信息

Institute of Infection and Global Health, University of Liverpool, Liverpool L69 3GA, UK.

出版信息

Am J Respir Crit Care Med. 2011 Jun 15;183(12):1674-9. doi: 10.1164/rccm.201009-1430OC. Epub 2011 Feb 4.

DOI:10.1164/rccm.201009-1430OC
PMID:21297072
Abstract

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.

摘要

背景

来自慢性囊性纤维化肺部感染的铜绿假单胞菌分离株表现出多种表型,表明其种群多样性广泛。

目的

我们旨在研究这种多样性在患者体内和患者之间是如何分布的,并通过时间研究多个患者中单菌株表型多样性的动态变化。

方法

对来自 10 名慢性囊性纤维化感染患者的 40 个痰液样本的铜绿假单胞菌分离株进行了一系列表型和基因型特征分析。分析了患者之间、患者内样本之间和样本内分离株之间的种群分化。

测量和主要结果

我们对来自广泛传播的流行株铜绿假单胞菌的 15 个特征进行了表征,这些菌株来自于 10 名慢性感染囊性纤维化的患者,这些患者在 2009 年被多次采样。总共分析了 43 个痰液样本,鉴定了 398 个利物浦流行株的单倍型。大多数表型多样性发生在患者体内。这种多样性具有高度动态性,表现为单倍型随时间快速转换。每个个体痰液样本中的铜绿假单胞菌种群都具有广泛的多样性。尽管我们观察到患者内样本之间的单倍型组成在几个月的间隔时间内发生了重大变化,但在加重期间,尽管使用了静脉内抗生素,其组成变化要小得多。我们的数据还突出了铜绿假单胞菌肺部感染期间患者体内种群生物学的一个重要特征,即肺部恶化期与群体感应控制的毒力因子吡咯喹啉醌过度产生之间存在相关性。

结论

这些结果大大提高了我们对囊性纤维化患者感染期间铜绿假单胞菌体内种群生物学的理解,并为吡咯喹啉醌产生与患者发病率之间的联系提供了体内证据。

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