Skip to content
DraconiticResearch
Search Sources API
197,787 studies31 sourcesUpdated 26 min ago
Peer-reviewedCC BYNature

Pervasive phosphorylation by phage T7 kinase disarms bacterial defences

  • Tara K. Bartolec1
  • Karin Mitosch2
  • Clément M. Potel1
  • Federico Corona1
  • Alessio Ling Jie Yang3,1
  • Nicolai Karcher1
  • Mira Lea Burtscher3,1
  • Alexandra Koumoutsi2,4
  • Isabelle Becher1
  • Lena Sarah Müller1
  • Jacob Bobonis5,2
  • Manjeet Kumar6,1
3 more authors
  • Marco Galardini7,8
  • Athanasios Typas9,10
  • Mikhail M. Savitski11,12
12 affiliations
  1. 1Molecular Systems Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
  2. 2Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
  3. 3Collaboration for joint PhD degree between EMBL and Heidelberg University, Faculty of Biosciences, Heidelberg, Germany
  4. 4Microbial Automation & Culturomics Core Facility, European Molecular Biology Laboratory, Heidelberg, Germany
  5. 5Division of Microbial Ecology, Centre for Microbiology and Environmental Systems Science, University of Vienna, Vienna, Austria
  6. 6Florida Research and Innovation Center, Cleveland Clinic, Port St Lucie, FL, USA
  7. 7Cluster of Excellence RESIST (EXC 2155), Hannover Medical School (MHH), Hannover, Germany
  8. 8Institute for Molecular Bacteriology, TWINCORE Centre for Experimental and Clinical Infection Research, Hannover, Germany
  9. 9Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany. [email protected]
  10. 10Molecular Systems Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany. [email protected]
  11. 11Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany. [email protected]
  12. 12Molecular Systems Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany. [email protected]
Open at sourceDOICite

Abstract

Bacteria and bacteriophages are in a constant arms race to develop defence and anti-defence systems, respectively. Currently known phage-encoded anti-defence systems are specific to the activity of the targeted bacterial defence system. Here we identify a mechanism by which the T7 bacteriophage broadly counteracts bacterial defences using protein phosphorylation. Its kinase (T7K), which has been reported to redirect the function of a few host proteins 1–5 , is actually a hyperpromiscuous dual-specificity kinase that phosphorylates nearly all host and phage proteins during infection. The scale of phosphorylation vastly exceeds known phosphosites in Escherichia coli , has no sequence motif specificity and results in a higher proteome-wide phosphorylation density than mammalian cells with around 500 kinases. Stoichiometry analysis of phosphorylation sites revealed strong bias in T7K activity towards nucleic-acid-binding substrates mediated by its C-terminal DNA-binding domain. This highly stoichiometric phosphorylation enables the deactivation of DNA-targeting or DNA-containing bacterial defence systems. We provide mechanistic insights into how T7K weakens DNA-containing Retron-Eco9 through specific phosphorylation events, with single phosphomimetic mutations in key sites of the toxin abolishing defence. Moreover, by screening a large collection of E. coli strains, we provide evidence of broad anti-defence abilities of T7K in nature, as counteracted strains contain diverse bacterial defence systems. T7K homologues are found almost exclusively in phages, with hyperpromiscuous kinase activity probably being enabled by a divergent DFG-like motif in the catalytic centre.

Related

  1. Phosphorylation by the PknB Serine/Threonine Kinase Stimulates Dimer Formation by WalR.
    Marina Suppi, Ian R Monk, Liam K R Sharkey +9
    BiochemistryPeer-reviewedCC BY-NC-NDFull textGenetics & genomicsEurope PMC
  2. Map-based cloning and functional validation of Xa50, a wall-associated kinase gene conferring broad-spectrum bacterial blight resistance in rice
    Meng Zhang, Meng Yuan
    Molecular Breeding : New Strategies in Plant ImprovementPeer-reviewedLicence not statedFull textPlant biologyPMC
  3. Hopeaphenol targets histidine kinase signaling across kingdoms to suppress bacterial virulence and potentiate plant immunity
    J. Kang, N. Yoo, T. Karasov +4
    bioRxivPreprintCC BY-NC-NDFull textPlant biologybioRxiv
  4. Early maturation of host antimicrobial peptide defences is associated with host–pathogen coexistence
    Phillip A. Jervis, Gonçalo M. Rosa, Kieran A. Bates +21
    Nature Chemical BiologyPeer-reviewedCC BY 4.0Full textMicrobiologyPMC
  5. Calcium Tunneling: A Pervasive Signaling Module Mediated by Coupling Store-Operated Ca2+ Entry and Endoplasmic Reticulum Ca2+ Release
    Raphael Courjaret, Khaled Machaca
    Cold Spring Harbor Perspectives in BiologyPreprintLicence not statedFull text2 citedCell biologyPMC

Cite

BibTeXRIS
BibTeX
@article{bartolec2026pervasive,
  title = {{Pervasive phosphorylation by phage T7 kinase disarms bacterial defences}},
  author = {Tara K. Bartolec and Karin Mitosch and Clément M. Potel and Federico Corona and Alessio Ling Jie Yang and Nicolai Karcher and Mira Lea Burtscher and Alexandra Koumoutsi and Isabelle Becher and Lena Sarah Müller and Jacob Bobonis and Manjeet Kumar and Marco Galardini and Athanasios Typas and Mikhail M. Savitski},
  journal = {Nature},
  year = {2026},
  month = aug,
  doi = {10.1038/s41586-026-10934-5},
  url = {https://doi.org/10.1038/s41586-026-10934-5},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Pervasive phosphorylation by phage T7 kinase disarms bacterial defences
AU  - Tara K. Bartolec
AU  - Karin Mitosch
AU  - Clément M. Potel
AU  - Federico Corona
AU  - Alessio Ling Jie Yang
AU  - Nicolai Karcher
AU  - Mira Lea Burtscher
AU  - Alexandra Koumoutsi
AU  - Isabelle Becher
AU  - Lena Sarah Müller
AU  - Jacob Bobonis
AU  - Manjeet Kumar
AU  - Marco Galardini
AU  - Athanasios Typas
AU  - Mikhail M. Savitski
PY  - 2026
DA  - 2026/08/19
JO  - Nature
DO  - 10.1038/s41586-026-10934-5
UR  - https://doi.org/10.1038/s41586-026-10934-5
AB  - Bacteria and bacteriophages are in a constant arms race to develop defence and anti-defence systems, respectively. Currently known phage-encoded anti-defence systems are specific to the activity of the targeted bacterial defence system. Here we identify a mechanism by which the T7 bacteriophage broadly counteracts bacterial defences using protein phosphorylation. Its kinase (T7K), which has been reported to redirect the function of a few host proteins 1–5 , is actually a hyperpromiscuous dual-specificity kinase that phosphorylates nearly all host and phage proteins during infection. The scale of phosphorylation vastly exceeds known phosphosites in Escherichia coli , has no sequence motif specificity and results in a higher proteome-wide phosphorylation density than mammalian cells with around 500 kinases. Stoichiometry analysis of phosphorylation sites revealed strong bias in T7K activity towards nucleic-acid-binding substrates mediated by its C-terminal DNA-binding domain. This highly stoichiometric phosphorylation enables the deactivation of DNA-targeting or DNA-containing bacterial defence systems. We provide mechanistic insights into how T7K weakens DNA-containing Retron-Eco9 through specific phosphorylation events, with single phosphomimetic mutations in key sites of the toxin abolishing defence. Moreover, by screening a large collection of E. coli strains, we provide evidence of broad anti-defence abilities of T7K in nature, as counteracted strains contain diverse bacterial defence systems. T7K homologues are found almost exclusively in phages, with hyperpromiscuous kinase activity probably being enabled by a divergent DFG-like motif in the catalytic centre.
SN  - 0028-0836
SN  - 1476-4687
ER  -