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染色体DNA缺失赋予铜绿假单胞菌噬菌体抗性。

Chromosomal DNA deletion confers phage resistance to Pseudomonas aeruginosa.

作者信息

Le Shuai, Yao Xinyue, Lu Shuguang, Tan Yinling, Rao Xiancai, Li Ming, Jin Xiaolin, Wang Jing, Zhao Yan, Wu Nicholas C, Lux Renate, He Xuesong, Shi Wenyuan, Hu Fuquan

机构信息

1] Department of Microbiology, Third Military Medical University, Chongqing, 400038, China [2] School of Dentistry, University of California, Los Angeles, CA, 90095, USA.

Department of Microbiology, Third Military Medical University, Chongqing, 400038, China.

出版信息

Sci Rep. 2014 Apr 28;4:4738. doi: 10.1038/srep04738.

Abstract

Bacteria develop a broad range of phage resistance mechanisms, such as prevention of phage adsorption and CRISPR/Cas system, to survive phage predation. In this study, Pseudomonas aeruginosa PA1 strain was infected with lytic phage PaP1, and phage-resistant mutants were selected. A high percentage (~30%) of these mutants displayed red pigmentation phenotype (Red mutant). Through comparative genomic analysis, one Red mutant PA1r was found to have a 219.6 kb genomic fragment deletion, which contains two key genes hmgA and galU related to the observed phenotypes. Deletion of hmgA resulted in the accumulation of a red compound homogentisic acid; while A galU mutant is devoid of O-antigen, which is required for phage adsorption. Intriguingly, while the loss of galU conferred phage resistance, it significantly attenuated PA1r in a mouse infection experiment. Our study revealed a novel phage resistance mechanism via chromosomal DNA deletion in P. aeruginosa.

摘要

细菌进化出多种噬菌体抗性机制,如防止噬菌体吸附和CRISPR/Cas系统,以在噬菌体捕食中存活。在本研究中,铜绿假单胞菌PA1菌株被裂解性噬菌体PaP1感染,并筛选出噬菌体抗性突变体。这些突变体中高比例(约30%)表现出红色色素沉着表型(红色突变体)。通过比较基因组分析,发现一个红色突变体PA1r有一个219.6 kb的基因组片段缺失,其中包含与观察到的表型相关的两个关键基因hmgA和galU。hmgA的缺失导致红色化合物尿黑酸积累;而galU突变体缺乏噬菌体吸附所需的O抗原。有趣的是,虽然galU的缺失赋予了噬菌体抗性,但在小鼠感染实验中它显著减弱了PA1r的致病性。我们的研究揭示了铜绿假单胞菌中一种通过染色体DNA缺失产生的新型噬菌体抗性机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/133d/4001099/d395245375e6/srep04738-f1.jpg

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