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高变异性铜绿假单胞菌囊性纤维化分离株中MutS的序列变异性及功能分析

Sequence variability and functional analysis of MutS of hypermutable Pseudomonas aeruginosa cystic fibrosis isolates.

作者信息

Hogardt Michael, Schubert Sören, Adler Kristin, Götzfried Monika, Heesemann Jürgen

机构信息

Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, Ludwig-Maximilians-Universität, Pettenkoferstrasse 9a, D-80336 München, Germany.

出版信息

Int J Med Microbiol. 2006 Aug;296(4-5):313-20. doi: 10.1016/j.ijmm.2005.12.018. Epub 2006 Mar 20.

Abstract

In this study, we investigated the variability of MutS among Pseudomonas aeruginosa recovered from cystic fibrosis (CF) patients. Sequencing of the mutS gene of 15 hypermutable P. aeruginosa isolates obtained from different patients revealed high rates of nucleotide substitutions as compared to that of strain PAO1. Significantly more synonymous than non-synonymous nucleotide substitutions have been found, indicating that generally MutS is highly conserved. The functional analysis of MutS variants by complementation of a PAO1 mutS mutant revealed 5 isolates with a defective MutS due to frameshift mutations or amino acid substitutions. This work supports the hypothesis that the respiratory tract of CF patients represents an environment that favors the selection of highly adaptive mutator phenotypes.

摘要

在本研究中,我们调查了从囊性纤维化(CF)患者分离出的铜绿假单胞菌中MutS的变异性。对从不同患者获得的15株高变异性铜绿假单胞菌分离株的mutS基因进行测序,结果显示与PAO1菌株相比,核苷酸替换率很高。发现同义核苷酸替换明显多于非同义核苷酸替换,这表明MutS通常高度保守。通过对PAO1 mutS突变体进行互补来对MutS变体进行功能分析,结果显示有5株分离株由于移码突变或氨基酸替换而导致MutS功能缺陷。这项工作支持了这样一种假说,即CF患者的呼吸道代表了一个有利于选择高度适应性突变体表型的环境。

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