A widespread phage-encoded kinase enables evasion of multiple host antiphage defence systems.

Autor: Jiang S; Department of Burn and Plastic Surgery, Shenzhen Key Laboratory of Microbiology in Genomic Modification and Editing and Application, Shenzhen Institute of Translational Medicine, Medical Innovation Technology Transformation Center of Shenzhen Second People's Hospital, Shenzhen University Medical School, The First Affiliated Hospital of Shenzhen University, Shenzhen, China.; Department of Gastroenterology, Ministry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Disease, TaiKang Center for Life and Medical Sciences, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan, China., Chen C; Department of Burn and Plastic Surgery, Shenzhen Key Laboratory of Microbiology in Genomic Modification and Editing and Application, Shenzhen Institute of Translational Medicine, Medical Innovation Technology Transformation Center of Shenzhen Second People's Hospital, Shenzhen University Medical School, The First Affiliated Hospital of Shenzhen University, Shenzhen, China., Huang W; Department of Burn and Plastic Surgery, Shenzhen Key Laboratory of Microbiology in Genomic Modification and Editing and Application, Shenzhen Institute of Translational Medicine, Medical Innovation Technology Transformation Center of Shenzhen Second People's Hospital, Shenzhen University Medical School, The First Affiliated Hospital of Shenzhen University, Shenzhen, China.; Department of Gastroenterology, Ministry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Disease, TaiKang Center for Life and Medical Sciences, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan, China., He Y; Department of Burn and Plastic Surgery, Shenzhen Key Laboratory of Microbiology in Genomic Modification and Editing and Application, Shenzhen Institute of Translational Medicine, Medical Innovation Technology Transformation Center of Shenzhen Second People's Hospital, Shenzhen University Medical School, The First Affiliated Hospital of Shenzhen University, Shenzhen, China.; Department of Gastroenterology, Ministry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Disease, TaiKang Center for Life and Medical Sciences, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan, China., Du X; Department of Burn and Plastic Surgery, Shenzhen Key Laboratory of Microbiology in Genomic Modification and Editing and Application, Shenzhen Institute of Translational Medicine, Medical Innovation Technology Transformation Center of Shenzhen Second People's Hospital, Shenzhen University Medical School, The First Affiliated Hospital of Shenzhen University, Shenzhen, China.; Department of Gastroenterology, Ministry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Disease, TaiKang Center for Life and Medical Sciences, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan, China., Wang Y; Department of Burn and Plastic Surgery, Shenzhen Key Laboratory of Microbiology in Genomic Modification and Editing and Application, Shenzhen Institute of Translational Medicine, Medical Innovation Technology Transformation Center of Shenzhen Second People's Hospital, Shenzhen University Medical School, The First Affiliated Hospital of Shenzhen University, Shenzhen, China.; Department of Gastroenterology, Ministry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Disease, TaiKang Center for Life and Medical Sciences, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan, China., Ou H; Department of Burn and Plastic Surgery, Shenzhen Key Laboratory of Microbiology in Genomic Modification and Editing and Application, Shenzhen Institute of Translational Medicine, Medical Innovation Technology Transformation Center of Shenzhen Second People's Hospital, Shenzhen University Medical School, The First Affiliated Hospital of Shenzhen University, Shenzhen, China., Deng Z; Department of Gastroenterology, Ministry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Disease, TaiKang Center for Life and Medical Sciences, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan, China., Xu C; Department of Gastroenterology, Ministry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Disease, TaiKang Center for Life and Medical Sciences, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan, China., Jiang L; Department of Burn and Plastic Surgery, Shenzhen Key Laboratory of Microbiology in Genomic Modification and Editing and Application, Shenzhen Institute of Translational Medicine, Medical Innovation Technology Transformation Center of Shenzhen Second People's Hospital, Shenzhen University Medical School, The First Affiliated Hospital of Shenzhen University, Shenzhen, China., Wang L; Department of Gastroenterology, Ministry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Disease, TaiKang Center for Life and Medical Sciences, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan, China.; Department of Respiratory Diseases, Institute of Pediatrics, Shenzhen Children's Hospital, Shenzhen, China., Chen S; Department of Burn and Plastic Surgery, Shenzhen Key Laboratory of Microbiology in Genomic Modification and Editing and Application, Shenzhen Institute of Translational Medicine, Medical Innovation Technology Transformation Center of Shenzhen Second People's Hospital, Shenzhen University Medical School, The First Affiliated Hospital of Shenzhen University, Shenzhen, China. shichen@email.szu.edu.cn.; Department of Gastroenterology, Ministry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Disease, TaiKang Center for Life and Medical Sciences, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan, China. shichen@email.szu.edu.cn.
Jazyk: angličtina
Zdroj: Nature microbiology [Nat Microbiol] 2024 Dec; Vol. 9 (12), pp. 3226-3239. Date of Electronic Publication: 2024 Nov 06.
DOI: 10.1038/s41564-024-01851-2
Abstrakt: DNA degradation (Dnd) is a widespread bacterial antiphage defence system that relies on DNA phosphorothioate (PT) modification for self/non-self discrimination and subsequent degradation of unmodified DNA. Phages employ counterstrategies to evade host immunity, but anti-Dnd immunity has not been characterized. Here we report an immune evasion protein encoded by the Salmonella phage JSS1 that contributes to subverting Dnd and other defence systems. Using quantitative proteomic and phosphoproteomic analyses, we show that the protein JSS1_004 employs N-terminal Ser/Thr/Tyr protein kinase activity to catalyse the multisite phosphorylation of host DndFGH. Notably, JSS1_004 also phosphorylates other bacterial immune systems to varying degrees, including CRISPR‒Cas, QatABCD, SIR2+HerA and DUF4297+HerA. Given that JSS1_004 and its homologues are widespread in phylogenetically diverse phages, we suggest that this strategy constitutes a family of immune evasion proteins that increases the chances of phage proliferation even when a host deploys multiple defence systems.
Competing Interests: Competing interests: Authors L.W., S.C., C.C. and S.J. have filed a Chinese patent application (202410735378X) on the basis of the findings in the paper. The other authors declare no competing interests.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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