Coxiella effector protein CvpF subverts RAB26-dependent autophagy to promote vacuole biogenesis and virulence

Fernande Ayenoue Siadous (1) , Franck Cantet (1) , Erin van Schaik (2) , Mélanie Burette (1) , Julie Allombert (3, 1) , Anissa Lakhani (1) , Boris Bonaventure (1) , Caroline Goujon (1) , James Samuel (2) , Matteo Bonazzi (1) , Eric Martinez (1)

1 IRIM - Institut de Recherche en Infectiologie de Montpellier
2 Texas A&M University Health Science Center
3 LegioPath - Pathogenèse des légionelles- Legionella pathogenesis

Coxiella burnetii, the etiological agent of the zoonosis Q fever, replicates inside host cells within a large vacuole displaying autolysosomal characteristics. The development of this compartment is mediated by bacterial effectors, which interfere with a number of host membrane trafficking pathways. By screening a Coxiella transposon mutant library, we observed that transposon insertions in cbu0626 led to intra- cellular replication and vacuole biogenesis defects. Here, we demonstrate that CBU0626 is a novel member of the Coxiella vacuolar protein (Cvp) family of effector proteins, which is translocated by the Dot/Icm secretion system and localizes to vesicles with autolysosomal features as well as Coxiella- containing vacuoles (CCVs). We thus renamed this effector CvpF for Coxiella vacuolar protein F. CvpF specifically interacts with the host small GTPase RAB26, leading to the recruitment of the autophago- somal marker MAP1LC3B/LC3B (microtubule associated protein 1 light chain 3 beta) to CCVs. Importantly, cvpF::Tn mutants were highly attenuated compared to wild-type bacteria in the SCID mouse model of infection, highlighting the importance of CvpF for Coxiella virulence. These results suggest that CvpF manipulates endosomal trafficking and macroautophagy/autophagy induction for optimal C. burnetii vacuole biogenesis.

Domaines: Biochimie, Biologie Moléculaire; Biologie cellulaire; Microbiologie et Parasitologie

Fernande Ayenoue Siadous, Franck Cantet, Erin van Schaik, Mélanie Burette, Julie Allombert, et al.. Coxiella effector protein CvpF subverts RAB26-dependent autophagy to promote vacuole biogenesis and virulence. Autophagy, 2020, pp.1 - 17. ⟨10.1080/15548627.2020.1728098⟩. ⟨hal-02988654⟩