AUTHOR=Mansilla Pareja María E. , Bongiovanni Antonino , Lafont Frank , Colombo María I. 

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

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 7 - 2017

YEAR=2017

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2017.00112

DOI=10.3389/fcimb.2017.00112

ISSN=2235-2988

ABSTRACT=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.