A new publication published in Nature Communications describes how bacterial virulence can be adopted to the cellular metabolic state by lysine acetylation of virulence factors.
The study was conducted by PhD student Ole Schmöker in the group of Prof. Michael Lammers in course of the research training group RTG-PRO “Proteases in pathogen and host: importance in infection and inflammation“ with contributions of several research groups of University of Greifswald, including Prof. Uwe Bornscheuer, Prof. Uwe Völker and Prof. Elke Krüger, as well as Prof. Kozjak-Pavlovic from University Würzburg and Prof. Kay Hofmann from University of Cologne.
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 acetyltransferase 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.
Link to the publication: https://www.nature.com/articles/s41467-026-72244-8