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 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 and as a consequence being structurally incompatible with SUMO1 binding. We provide a model for regulation of SnCE1-mediated virulence by lysine acetylation modulating autoproteolytic processing and subcellular distribution in the host cell. SnCE1 localizes to the endoplasmic reticulum in human cells and results in formation of fragmented mitochondria. Our data provide mechanistic insights how lysine acetylation of virulence factors is used to reprogram virulence adjusting it to the host cells’ metabolic state.