Legionella employs the multimodal ubiquitination of Sec22b to modulate SNARE pairing

Legionella pneumophila establishes its replicative niche through the deployment of multiple effector proteins. During this process, the host v-SNARE Sec22b is recruited from the endoplasmic reticulum to bacterial phagosomes and engages in non-canonical pairings with plasma membrane syntaxins. We previously reported that Sec22b undergoes polyubiquitination at early stages of infection and that the Legionella deubiquitinase LotB cleaves polyubiquitin chains from Sec22b, resulting in Sec22b dissociating from syntaxin 3. The current study investigates the molecular mechanisms underlying Sec22b ubiquitination and its physiological function during L. pneumophila infection. SdeA, a Legionella ubiquitin ligase, is identified as a crucial factor in promoting Sec22b polyubiquitination. SdeA catalyzes the conjugation of phosphoribosyl-linked ubiquitin to serine 137 of Sec22b; subsequently, the canonical ubiquitin system appears to polyubiquitinate Sec22b. Additionally, multimodal ubiquitination of Sec22b facilitates non-canonical SNARE pairing during early infection. This research outlines a bacterial strategy for modulating SNARE protein dynamics via reversible post-translational modifications.