Legionella Manipulates Non-canonical SNARE Pairing Using a Bacterial Deubiquitinase

Tomoe Kitao,Kyoichiro Taguchi,Shintaro Seto,Kohei Arasaki,Hiroki Ando,Hiroki Nagai,Tomoko Kubori

doi:10.1016/j.celrep.2020.108107

Abstract

The intracellular bacterial pathogen Legionella pneumophila uses many effector proteins delivered by the bacterial type IV secretion system (T4SS) to hijack the early secretory pathway to establish its replicative niche, known as the Legionella-containing vacuole (LCV). On LCV biogenesis, the endoplasmic reticulum (ER) vesicular soluble N-ethylmaleimide-sensitive factor attachment protein receptors (v-SNARE) Sec22b is recruited to the bacterial phagosome and forms non-canonical pairings with target membrane SNAREs (t-SNAREs) from the plasma membrane. Here, we identify a Legionella deubiquitinase (DUB), LotB, that can modulate the early secretory pathway by interacting with coatomer protein complex I (COPI) vesicles when ectopically expressed. We show that Sec22b is ubiquitinated upon L.pneumophila infection in a T4SS-dependent manner and that, subsequently, LotB deconjugates K63-linked ubiquitins from Sec22b. The DUB activity of LotB stimulates dissociation of the t-SNARE syntaxin 3 (Stx3) from Sec22b, which resides on the LCV. Our study highlights a bacterial strategy manipulating the dynamics of infection-induced SNARE pairing using a bacterial DUB.

Highlights

Legionella pneumophila is an intravacuolar bacterial pathogen that causes a severe form of pneumonia known as Legionnaires’ disease
After the COPII coat is removed from the COPII vesicles, the vesicles fuse with ERGolgi intermediate compartments (ERGICs), which are implicated in cargo sorting in mammalian cells
LotB Is a DUB Specific to K63-Linked Ubiquitin Chains LotB/Lpg1621/Ceg23 is translocated into host cells in a T4SSdependent manner (Zusman et al, 2007)

Summary

Introduction

Legionella pneumophila is an intravacuolar bacterial pathogen that causes a severe form of pneumonia known as Legionnaires’ disease. To survive in host cells, L. pneumophila creates a specialized vacuole as a replicative niche by hijacking host trafficking pathways It intercepts the traffic of early secretory vesicles between the endoplasmic reticulum (ER) and the Golgi apparatus (Asrat et al, 2014; Derreand Isberg, 2004; Kagan and Roy, 2002). These early secretory vesicles fuse with the bacterial phagosome and convert it into an ER-like organelle known as a Legionella-containing vacuole (LCV) (Horwitz, 1983a, 1983b; Robinson and Roy, 2006; Swanson and Isberg, 1995; Tilney et al, 2001). Given the crucial roles of Sar, ARF, and Rab in LCV biogenesis (Kagan and Roy, 2002), it is thought that L. pneumophila intercepts ER-Golgi traffic

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