Reprogramming of bacterial virulence by lysine acetylation
Gram-negative bacteria use a plethora of virulence factors to infect eukaryotic cells. CE-clan protease-related virulence factors were reported to act as deubiquitinases/ubiquitin-like specific proteases. Some have an additional acetyl-transferase activity. The molecular mechanisms underlying this dual activity and the physiological consequences are only marginally understood. Here, we report crystal structures for the Simkania negevensis virulence factor SnCE1 in apo-states and in complex with SUMO1. We confirm SnCE1 acting as an efficient deSUMOylase and discover an intrinsic autoacetyltransferase activity. Acetylation impairs SnCE1 tetramer formation structurally being incompatible with SUMO1 binding. We provide a model for regulation of SnCE1-mediated virulence by lysine acetylation modulating autoproteolytic processing and its subcellular distribution in the host cell. SnCE1 localizes to the endoplasmic reticulum in human cells and increases fragmentation of mitochondria. Our data provide mechanistic insights into how lysine acetylation of virulence factors is used to reprogram virulence adjusting it to the host cells' metabolic state.
Authors
- N. Kara (ORCID: https://orcid.org/0000-0002-6618-379X)
- Marcus Krüger (ORCID: https://orcid.org/0000-0002-5846-6941)
- Leif Steil (ORCID: https://orcid.org/0000-0002-0733-8421)
- Vera Kozjak‐Pavlovic (ORCID: https://orcid.org/0000-0001-9658-7018)
- Christian Hentschker
- Jens Hoppen
- Uwe T. Bornscheuer (ORCID: https://orcid.org/0000-0003-0685-2696)
- Leona Berndt (ORCID: https://orcid.org/0000-0002-2864-6386)
- Michael Lammers (ORCID: https://orcid.org/0000-0003-4168-4640)
- Jan‐Wilm Lackmann (ORCID: https://orcid.org/0000-0001-8182-8034)
- Sabrina Schulze (ORCID: https://orcid.org/0000-0002-0122-5688)
- Britta Girbardt
- Lea-Maria Mayer
- Ruba Al‐Abdulla (ORCID: https://orcid.org/0000-0002-5194-9801)
- Mark Doerr (ORCID: https://orcid.org/0000-0003-3270-6895)
- Stefan Kemnitz
- Uwe Völker (ORCID: https://orcid.org/0000-0002-5689-3448)
- Kay Hofmann (ORCID: https://orcid.org/0000-0002-2289-9083)
- Heike Junker
- Gottfried J. Palm
- Elke Krüger (ORCID: https://orcid.org/0000-0002-2551-242X)
- Ole Schmöker (ORCID: https://orcid.org/0009-0005-4754-8246)
- Klara Garz
- Katrin Schoknecht
- Leonie Speth
- Xenia Schöps
- Vanessa Lachmayer
- Sophie Wolfgramm
- Stefan Müller
Institutions
- University of Cologne (DE)
- University of Würzburg (DE)
- Universitätsmedizin Greifswald (DE)
- Universität Greifswald (DE)
- Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (DE)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-04-27
- DOI
- https://doi.org/10.1038/s41467-026-72244-8
- Citations
- 1
- Primary Topic
- Ubiquitin and proteasome pathways
- Type
- article
- Field-Weighted Citation Impact
- 11.47
Funders
- Deutsche Forschungsgemeinschaft
- Universität Greifswald
- Deutsches Elektronen-Synchrotron