Abstract
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.
Acknowledgements
We thank the group of Prof. Frauke Melchior and Dr. Annette Flotho, Heidelberg University, for sending recombinant RanGAP1-SUMO1 and a human RanGAP1 antibody. We thank Dr. Thomas Hermanns, University Cologne, for providing plasmids encoding for SnCE1-5, SENP1, SENP6 and of Ub/SUMO1/SUMO3 activity-based probes. We thank Felix Glinka for providing the plasmid encoding yeast Ulp1. We thank Kathrin Krassow for expert secretary assistance. This work was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)-grant No. 443535983 (Research Training Group 2719; RTG 2719; M.L.), Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) grant No. 445120888 (INST 292/156-1 FUGG; M.L.) and grant No. 441529220 (INST 292/154-1 FUGG; M.L.). Support for the publication fee was provided by University of Greifswald’s publication fund. We thank HZB/BESSY in Berlin and EMBL/DESY in Hamburg for continuous support in X-ray data collection.
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Schmöker, O., Girbardt, B., Schulze, S. et al. Reprogramming of bacterial virulence by lysine acetylation. Nat Commun (2026). https://doi.org/10.1038/s41467-026-72244-8
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DOI: https://doi.org/10.1038/s41467-026-72244-8
