1/11 - With @KMitosch and Clément Potel + colleagues in @savitski_lab @TypasLab @embl, I’m very happy to share our discovery of a hyper-promiscuous phage protein kinase (T7K) which broadly deactivates bacterial defenses!

RT @TypasLab: Excited for New Approaches and Concepts in Microbiology 2025 (#EESMicrobiology) with sessions on Bacterial systems biology, B….

RT @savitski_lab: Want to know how the ligands interact with proteins beyond model human cell lines? Interested in membrane targets? Check….

RT @savitski_lab: We are very happy to present our work on N-glycoproteomics!🍬 Our method enables the selective enrichment and precise quan….

RT @savitski_lab: Exciting opening at the proteomics core facility at EMBL! Please spread, apply and reach out!

RT @savitski_lab: New preprint - our latest close collaboration with @TypasLab @embl on phage-host interactions, led by @TaraBartolec, @KMi….

RT @TypasLab: Excited to share our preprint with @savitski_lab led by @TaraBartolec, @KMitosch & Clément Potel! We uncovered a mechanism by….

11/11 - Thanks to all involved - what a super collaboration between @embl @savitski_lab and @TypasLab, with @YangAlessio, @Miralea10, @J_Bobonis, @NicolaiKarcher, @mgalactus, @EMBLHeidelberg / #phage #proteomics #phosphorylation #microbiology #PTMs.

10/11 - T7K affected infectivity in nearly half of tested strains! It sometimes even gave >1000-fold advantages to the phage. And none of these strains had Retron-Eco9 or DarTG1, so it is likely that there are many, many more T7K-sensitive systems to be described.

9/11 - So maybe the domesticated K-12 strain (which has lost many defense systems) wasn’t the best model for studying the function of T7K. We assessed this by screening a panel of natural isolates, which harbour a very diverse array of anti-phage defense systems.

8/11 - It seemed so, w/ clear phenotypes for T7K when we armed K-12 w/ plasmids encoding DNA-related defense systems Retron-Eco9 & DarTG1. Both had critical functional residues on their surface, and phosphorylation events deposited by T7K abolished their ability to defend!.

7/11 - The stoichiometry results gave us a major clue as to what was really going on - bacterial anti-phage defense systems often work by sensing and/or targeting the phage’s nucleic acids. Perhaps the kinase can brute-force deactivate bacterial defenses?.

6/11 - But the T7K gene was reported to be largely dispensable when T7 infected lab strain K-12. Why keep a hyper-promiscuous kinase around if its function is simply to optimise host takeover (translation, transcription)? Doesn’t this activity also hinder T7’s infection cycle?.

5/11 - This is achieved through the protein’s C-terminal domain - a long, highly charged and extended alpha-helical region which resembles a histone tail and binds DNA, which colocalises + focuses the loose-canon kinase’s activity towards nucleic acid-binding proteins.

4/11 - But how do you interpret a kinase’s role if it phosphorylates EVERYTHING? We tried estimating phosphorylation stoichiometry and found that there was some order to the madness - nucleic-acid binding proteins were much more heavily modified than the rest of the proteome.

3/11 - T7 infection induced a massive wave of phosphorylation - dependent on T7K! We found that T7K is incredibly promiscuous, exceeding the combined activity of 500+ human kinases in just 5 min! Promiscuity is achieved through dual-specificity (S/T & Y) + no sequence motif.

2/11 - T7K has been studied since the 70s w/ a handful of (v. abundant) substrates identified using traditional biochem (SDS-PAGE, radio-labelling, WBs). We studied T7 w/ modern bacterial phosphoproteomics (better sensitivity + specificity) and found a COMPLETELY different story.

RT @naturemethods: .@theliulab @MRuwolt @diogobor @milanzord @absea_bio @Julia_RtaAn introduce a XL-MS standard based on human proteins or….

RT @MRuwolt: Our DSSO xlinked PPI benchmarking dataset (PXD042173) and Scout ( are finally published ( https://t.co/….

RT @joeBondyDenomy: Did you know that bacteria remember their past for many generations? In this new preprint from us (@VillaniAlexis and S….