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