Bacteriophage protein Dap1 regulates evasion of antiphage immunity and Pseudomonas aeruginosa virulence impacting phage therapy in mice

Le, Shuai1,2; Wei, Leilei3,4; Wang, Jing1,2; Tian, Fang4; Yang, Qian5; Zhao, Jingru5; Zhong, Zhuojun1,2; Liu, Jiazhen1,2; He, Xuesong6; Zhong, Qiu3; Lu, Shuguang1,2; Liang, Haihua4,7

2024-06-01

10.1038/s41564-024-01719-5

NATURE MICROBIOLOGY   影响因子和分区

2058-5276

Bacteriophages have evolved diverse strategies to overcome host defence mechanisms and to redirect host metabolism to ensure successful propagation. Here we identify a phage protein named Dap1 from Pseudomonas aeruginosa phage PaoP5 that both modulates bacterial host behaviour and contributes to phage fitness. We show that expression of Dap1 in P. aeruginosa reduces bacterial motility and promotes biofilm formation through interference with DipA, a c-di-GMP phosphodiesterase, which causes an increase in c-di-GMP levels that trigger phenotypic changes. Results also show that deletion of dap1 in PaoP5 significantly reduces genome packaging. In this case, Dap1 directly binds to phage HNH endonuclease, prohibiting host Lon-mediated HNH degradation and promoting phage genome packaging. Moreover, PaoP5 Delta dap1 fails to rescue P. aeruginosa-infected mice, implying the significance of dap1 in phage therapy. Overall, these results highlight remarkable dual functionality in a phage protein, enabling the modulation of host behaviours and ensuring phage fitness.

SCI

英语

通讯

National Natural Science Foundation of China (National Science Foundation of China)["2021YFA0911200","2022YFC2304400","2022YFC2304401"] ; National Key Research and Development Program of China["32170188","32270175"] ; National Natural Science Foundation of China[20231120104808001]

Microbiology

Microbiology

WOS:001249554600001

NATURE PORTFOLIO

Web of Science

1.Army Med Univ, Key Lab Microbial Engn Educ Comm Chongqing, Coll Basic Med Sci, Dept Microbiol, Chongqing, Peoples R China
2.State Key Lab Trauma & Chem Poisoning, Chongqing, Peoples R China
3.Army Med Univ, Daping Hosp, Dept Lab Med, Chongqing, Peoples R China
4.Southern Univ Sci & Technol, Coll Med, Shenzhen, Peoples R China
5.Northwest Univ, Coll Life Sci, Xian, Peoples R China
6.ADA Forsyth Inst, Cambridge, MA USA
7.Southern Univ Sci & Technol, Univ Lab Metab & Hlth Guangdong, Shenzhen, Peoples R China

Le, Shuai,Wei, Leilei,Wang, Jing,et al. Bacteriophage protein Dap1 regulates evasion of antiphage immunity and Pseudomonas aeruginosa virulence impacting phage therapy in mice[J]. NATURE MICROBIOLOGY,2024.

Le, Shuai.,Wei, Leilei.,Wang, Jing.,Tian, Fang.,Yang, Qian.,...&Liang, Haihua.(2024).Bacteriophage protein Dap1 regulates evasion of antiphage immunity and Pseudomonas aeruginosa virulence impacting phage therapy in mice.NATURE MICROBIOLOGY.

Le, Shuai,et al."Bacteriophage protein Dap1 regulates evasion of antiphage immunity and Pseudomonas aeruginosa virulence impacting phage therapy in mice".NATURE MICROBIOLOGY (2024).