Control of lysogeny and antiphage defense by a prophage-encoded kinase-phosphatase module.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
23 Aug 2024
Historique:
received: 09 05 2024
accepted: 12 08 2024
medline: 23 8 2024
pubmed: 23 8 2024
entrez: 22 8 2024
Statut: epublish

Résumé

The filamentous 'Pf' bacteriophages of Pseudomonas aeruginosa play roles in biofilm formation and virulence, but mechanisms governing Pf prophage activation in biofilms are unclear. Here, we identify a prophage regulatory module, KKP (kinase-kinase-phosphatase), that controls virion production of co-resident Pf prophages and mediates host defense against diverse lytic phages. KKP consists of Ser/Thr kinases PfkA and PfkB, and phosphatase PfpC. The kinases have multiple host targets, one of which is MvaU, a host nucleoid-binding protein and known prophage-silencing factor. Characterization of KKP deletion and overexpression strains with transcriptional, protein-level and prophage-based approaches indicates that shifts in the balance between kinase and phosphatase activities regulate phage production by controlling MvaU phosphorylation. In addition, KKP acts as a tripartite toxin-antitoxin system that provides defense against some lytic phages. A conserved lytic phage replication protein inhibits the KKP phosphatase PfpC, stimulating toxic kinase activity and blocking lytic phage production. Thus, KKP represents a phosphorylation-based mechanism for prophage regulation and antiphage defense. The conservation of KKP gene clusters in >1000 diverse temperate prophages suggests that integrated control of temperate and lytic phage infection by KKP-like regulatory modules may play a widespread role in shaping host cell physiology.

Identifiants

pubmed: 39174532
doi: 10.1038/s41467-024-51617-x
pii: 10.1038/s41467-024-51617-x
doi:

Substances chimiques

Phosphoric Monoester Hydrolases EC 3.1.3.2
Viral Proteins 0
Protein Serine-Threonine Kinases EC 2.7.11.1

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

7244

Informations de copyright

© 2024. The Author(s).

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Auteurs

Yunxue Guo (Y)

Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, Innovation Academy of South China Sea Ecology and Environmental Engineering, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China.
Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou, China.
University of Chinese Academy of Sciences, Beijing, China.

Kaihao Tang (K)

Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, Innovation Academy of South China Sea Ecology and Environmental Engineering, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China.
Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou, China.

Brandon Sit (B)

Department of Microbiology, Harvard Medical School, Boston, MA, USA.
Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA.
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.

Jiayu Gu (J)

Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, Innovation Academy of South China Sea Ecology and Environmental Engineering, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China.
University of Chinese Academy of Sciences, Beijing, China.

Ran Chen (R)

Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, Innovation Academy of South China Sea Ecology and Environmental Engineering, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China.
Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou, China.

Xinqi Shao (X)

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, CAMS Key Laboratory for Prevention and Control of Hematological Disease Treatment Related Infection, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.

Shituan Lin (S)

Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, Innovation Academy of South China Sea Ecology and Environmental Engineering, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China.
University of Chinese Academy of Sciences, Beijing, China.

Zixian Huang (Z)

Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, Innovation Academy of South China Sea Ecology and Environmental Engineering, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China.
University of Chinese Academy of Sciences, Beijing, China.

Zhaolong Nie (Z)

Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, Innovation Academy of South China Sea Ecology and Environmental Engineering, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China.

Jianzhong Lin (J)

Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, Innovation Academy of South China Sea Ecology and Environmental Engineering, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China.
University of Chinese Academy of Sciences, Beijing, China.

Xiaoxiao Liu (X)

Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, Innovation Academy of South China Sea Ecology and Environmental Engineering, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China.
Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou, China.

Weiquan Wang (W)

Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, Innovation Academy of South China Sea Ecology and Environmental Engineering, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China.
University of Chinese Academy of Sciences, Beijing, China.

Xinyu Gao (X)

Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, Innovation Academy of South China Sea Ecology and Environmental Engineering, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China.
University of Chinese Academy of Sciences, Beijing, China.

Tianlang Liu (T)

Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, Innovation Academy of South China Sea Ecology and Environmental Engineering, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China.
University of Chinese Academy of Sciences, Beijing, China.

Fei Liu (F)

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, CAMS Key Laboratory for Prevention and Control of Hematological Disease Treatment Related Infection, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.

Hongbo R Luo (HR)

Boston Children's Hospital, Dana-Farber/Harvard Cancer Center, Boston, MA, USA.

Matthew K Waldor (MK)

Department of Microbiology, Harvard Medical School, Boston, MA, USA. mwaldor@bwh.harvard.edu.
Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA. mwaldor@bwh.harvard.edu.
Howard Hughes Medical Institute, Bethesda, MD, USA. mwaldor@bwh.harvard.edu.

Xiaoxue Wang (X)

Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, Innovation Academy of South China Sea Ecology and Environmental Engineering, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China. xxwang@scsio.ac.cn.
Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou, China. xxwang@scsio.ac.cn.
University of Chinese Academy of Sciences, Beijing, China. xxwang@scsio.ac.cn.

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