Alterations of the Coxiella burnetii Replicative Vacuole Membrane Integrity and Interplay with the Autophagy Pathway

Frontiers in Cellular and Infection Microbiology

a I.²  Mansilla Pareja, Marí³  Lafont, Frank⁴  a E.⁵  Bongiovanni, Antonino⁶  Colombo, Marí⁸ 

[1] Et de la Recherche MéCellular Microbiology and Physics of Infection Group—Center of Infection and Immunity of Lille, Centre National de la Recherche Scientifique, Institut Pasteur of Lille, UMR8204, Institut National de la SantéLaboratorio de Biología (IHEM), Universidad Nacional de Cuyo, CONICET, Facultad de Ciencias Méa Celular y Molecular—Instituto de Histología y Embriologídical U1019, Lille Regional Hospital, University Center, Universite Lille, Lille, France;dicas, Mendoza, Argentina

关键词: Coxiella burnetii;    Autophagy;    Galectins;    damage detection;    vacuole membrane;   

DOI  :  10.3389/fcimb.2017.00112

学科分类：生物科学（综合）

来源: Frontiers

【 摘 要 】

Coxiella burnetii, the etiologic agent of Q fever, is a Gram-negative obligate intracellular bacterium. It has been previously described that both the endocytic and autophagic pathways contribute to the Coxiella replicative vacuole (CRV) generation. Galectins are β-galactoside-binding lectins that accumulate in the cytosol before being secreted via a non-convencional secretory pathway. It has been shown that Galectin-3, -8, -9 monitor endosomal and lysosomal integrity and detects bacterial invasion by binding host glycans exposed on damaged vacuoles. Using microinjection of fluorescence-coupled dextrans, a FRET assay, and galectins distribution, we demonstrate that Coxiella infection actually damages the phagosomal/CRV membrane in a Dot/Icm-dependent manner. We have also shown the association of different adaptor molecules involved in autophagy to the limiting membrane of the CRV. Our results suggest that a population of the CRV loses transiently its acidic pH likely due to a membrane damage leading to recruitment of galectins. We show that these adaptor molecules allow the association of components of the autophagy machinery and, as a consequence we propose that the fusion of autophagic vesicles, facilitate the resealing of the damaged membranes.

【 授权许可】

CC BY