Cholesterol transporters and their role in the biogenesis of the vacuole where coxiella burnetii residence and multiplies

ORTIZ FLORES RM; DISTEL JS; BERÓN W,; ALBANES M

Mendoza

Congreso; XXXIV Reunión Científica Anual organizada por la Sociedad de Biología de Cuyo; 2016

Sociedad de Biología de Cuyo

Coxiella burnetii (Cb), the causative agent of ?Q fever? in humans, is an intracellular obligate pathogen that transits through the phagocytic pathway of host cell to form a Coxiella-containing vacuole (CCV). Very little is known about the relationship between CCV formation and host cell lipids during the intracellular bacterium trafficking. It is known that the membrane of CCV contains a high cholesterol concentration. The Niemann-Pick C1 (NPC1) is a glycoprotein located in the membrane of endolisosomal compartments. At steady state, NPC1 is synthesized in the ER and traffics toward the middle endolysosomal compartment where cholesterol is sorted to different intracellular compartment mediated by NPC1. ORP5 belong to a protein family called oxysterol-binding protein-related proteins. It is placed on cytosolic face of the endoplasmic reticulum. This protein is responsible for the transport of cholesterol and other lipids from the reticulum to endocytic compartment. The focus of this work is to study the effect of NPC1 and ORP5 overexpression on the biogenesis of the CCV. Considering the cells that overexpress NPC1 WT (wild type), small phagosomes containng Cb were observed. Similar results were obtained in cells overexpressing ORP5 WT. The overexpression of negative mutants of NPC1 or ORP5, a typical large vacuoles containing Cb were observed. We can conclude that the cholesterol transport proteins are involved in the formation of the vacuole where Coxiella burnetii reside and multiply.