IHEM   20887
INSTITUTO DE HISTOLOGIA Y EMBRIOLOGIA DE MENDOZA DR. MARIO H. BURGOS
Unidad Ejecutora - UE
artículos
Título:
The autophagic pathway is actively modulated by phase II Coxiella burnetii to efficiently replicate in the host cell.
Autor/es:
ROMANO, PATRICIA S.; GUTIERREZ, MAXIMILIANO G.; BERÓN, W.; RABINOVITCH, M.; COLOMBO, M. I.
Revista:
CELLULAR MICROBIOLOGY (PRINT)
Referencias:
Año: 2007 vol. 9 p. 891 - 909
ISSN:
1462-5814
Resumen:
The etiologic agent of Q fever Coxiella burnetii, is an intracellular obligate parasite that develops large vacuoles with phagolysosomal characteristics, containing multiple replicating bacteria. We have previously shown that Phase II Coxiella burnetii replicative vacuoles generated after 24-48 h post infection are decorated with the autophagic protein LC3. The aim of the present study was to examine, at earlier stages of infection, the distribution and roles of the small GTPases Rab5 and Rab7, markers of early and late endosomes, respectively, as well as of the protein LC3 on C. burnetii trafficking. Our results indicate that: 1) Coxiella phagosomes (CPh) acquire the two rab proteins sequentially during infection; 2) overexpression of a dominant negative mutant form of Rab5, but not of Rab7, impaired Coxiella entry, whereas both Rab5 and Rab7 dominant negative mutants inhibited vacuole formation; 3) Cph colocalized with the protein LC3 as early as 5 min after infection; acquisition of the protein appeared to be a bacterially driven process, since it was inhibited by the bacteriostatic antibiotic chloramphenicol; 4) C. burnetii delayed the arrival of the typical lysosomal protease cathepsin D to the CPh, a process that is increased by starvation-induced autophagy. Based on our results we propose that C. burnetii transits through the normal endo/phagocytic pathway but actively interacts with autophagosomes at early times after infection. This intersection with the autophagic pathway delays fusion with the lysosomal compartment possibly favoring the intracellular differentiation and survival of the bacteria.