Serine ubiquitination of SNAREs generates bacterial vacuoles and prevents their lysosomal fusion

Here we show that Legionella SidE effectors mediate phosphoribosyl-linked serine ubiquitination (PR-Ub) of the autophagic SNARE proteins STX17 and SNAP29. On the one hand, PR-Ub modification of STX17 enhances its interaction with ATG14L, which drives the recruitment of ER membranes to the bacterial vacuole in a PI3K-dependent manner and promotes the formation of bacterial replicative vacuoles. On the other hand, PR-Ub of SNAP29 inhibits the formation of the autophagosomal SNARE complex (STX17-SNAP29-VAMP8) by steric hindrance and thus prevents the fusion of STX17 + bacterial vacuoles with lysosomes.