Autophagy induction stimulates the development of the coxiella-replicative vacuole

VÁZQUEZ CRISTINA, GUTIÉRREZ MAXIMILIANO, MUNAFÓ DANIELA, ZOPPINO MARTÍN, BERÓN WALTER, RABINOVITCH M, AND COLOMBO MARÍA ISABEL

Iguazu Misiones Argentina

Congreso; XL Reunión Anual de la Sociedad Argentina de Bioquímica y Biología Molecular (SAIB); 2004

SAIB

Pathogens evolved mechanisms to invade host cellsand to multiply in the cytosol or in compositionallyand functionally customized membrane-bound compartments.Coxiella burnetii, the agent of Q fever inman is a Gram-negativeg-proteobacterium whichmultiplies in large, acidified, hydrolase-rich andfusogenic vacuoles with phagolysosomal-likecharacteristics. We reported previously thatC. burnetiiphase II replicative compartments are labelled byLC3, a protein specifically localized to autophagicvesicles. We show here that autophagy in Chinesehamster ovary cells, induced by amino acid deprivationprior to infection withCoxiellaincreased thenumber of infected cells, the size of the vacuoles, andtheir bacterial load. Furthermore, overexpression ofGFP-LC3 or of GFP-Rab24 – a protein also localizedto autophagic vacuoles – likewise accelerated thedevelopment ofCoxiella-vacuoles at early times afterinfection. However, overexpression of mutants ofthose proteins that cannot be targeted to autophagosomesdramatically decreased the number and sizeof the vacuoles in the first hours of infection, althoughby 48 h the infection was similar to that of non-transfectedcontrols. Overall, the results suggest that transitthrough the autophagic pathway increases theinfection withCoxiellaby providing a niche morefavourable to their initial survival and multiplication.