Chromosomal DNA deletion confers phage resistance to Pseudomonas aeruginosa

被引:86
作者
Le, Shuai [1 ,2 ]
Yao, Xinyue [1 ]
Lu, Shuguang [1 ]
Tan, Yinling [1 ]
Rao, Xiancai [1 ]
Li, Ming [1 ]
Jin, Xiaolin [1 ]
Wang, Jing [1 ]
Zhao, Yan [1 ]
Wu, Nicholas C. [3 ]
Lux, Renate [2 ]
He, Xuesong [2 ]
Shi, Wenyuan [2 ]
Hu, Fuquan [1 ]
机构
[1] Third Mil Med Univ, Dept Microbiol, Chongqing 400038, Peoples R China
[2] Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90095 USA
[3] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA
基金
中国国家自然科学基金;
关键词
BACTERIOPHAGE THERAPY; CAMPYLOBACTER-JEJUNI; GENOME; ADAPTATION; INFECTION; SYSTEM; GENE; GALU; LIPOPOLYSACCHARIDE; COEVOLUTION;
D O I
10.1038/srep04738
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 (similar to 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.
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页数:8
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