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

Autor: Le S; Department of Microbiology, College of Basic Medical Sciences, Key Laboratory of Microbial Engineering Under the Educational Committee in Chongqing, Army Medical University, Chongqing, China.; State Key Laboratory of Trauma and Chemical Poisoning, Chongqing, China., Wei L; Department of Laboratory Medicine, Daping Hospital, Army Medical University, Chongqing, China.; College of Medicine, Southern University of Science and Technology, Shenzhen, China., Wang J; Department of Microbiology, College of Basic Medical Sciences, Key Laboratory of Microbial Engineering Under the Educational Committee in Chongqing, Army Medical University, Chongqing, China.; State Key Laboratory of Trauma and Chemical Poisoning, Chongqing, China., Tian F; College of Medicine, Southern University of Science and Technology, Shenzhen, China., Yang Q; College of Life Sciences, Northwest University, Xi'an, China., Zhao J; College of Life Sciences, Northwest University, Xi'an, China., Zhong Z; Department of Microbiology, College of Basic Medical Sciences, Key Laboratory of Microbial Engineering Under the Educational Committee in Chongqing, Army Medical University, Chongqing, China.; State Key Laboratory of Trauma and Chemical Poisoning, Chongqing, China., Liu J; Department of Microbiology, College of Basic Medical Sciences, Key Laboratory of Microbial Engineering Under the Educational Committee in Chongqing, Army Medical University, Chongqing, China.; State Key Laboratory of Trauma and Chemical Poisoning, Chongqing, China., He X; The ADA Forsyth Institute, Cambridge, MA, USA., Zhong Q; Department of Laboratory Medicine, Daping Hospital, Army Medical University, Chongqing, China., Lu S; Department of Microbiology, College of Basic Medical Sciences, Key Laboratory of Microbial Engineering Under the Educational Committee in Chongqing, Army Medical University, Chongqing, China.; State Key Laboratory of Trauma and Chemical Poisoning, Chongqing, China., Liang H; College of Medicine, Southern University of Science and Technology, Shenzhen, China. lianghh@sustech.edu.cn.; University Laboratory of Metabolism and Health of Guangdong, Southern University of Science and Technology, Shenzhen, China. lianghh@sustech.edu.cn.
Jazyk: angličtina
Zdroj: Nature microbiology [Nat Microbiol] 2024 Jul; Vol. 9 (7), pp. 1828-1841. Date of Electronic Publication: 2024 Jun 17.
DOI: 10.1038/s41564-024-01719-5
Abstrakt: 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, PaoP5Δdap1 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.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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