BOCCO JOSE LUIS
Congresos y reuniones científicas
Título:
Microorganisms and Autophagy: the Autophagic response, a pathogen driven process
Autor/es:
ROMANO, P; SAKA, HA.; GUTIERREZ, M.; ZOPPINO, M.; BOCCO, J. L.; COLOMBO, M. I.
Lugar:
Centro Cultural Parque de España - Rosario, Argentina.
Reunión:
Congreso; XLII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2006
Institución organizadora:
Sociedad Argentina de Investigación en Bioquímica y Biología Molecular
Resumen:
Coxiella burnetii is an intracellular obligate parasite that resides and replicates in large vacuoles with autophagolysosomal characteristics. We have examined, at earlier stages of infection, the distribution and roles of the small GTPases Rab5 and Rab7 on C. burnetii trafficking. Coxiella phagosomes (CPh) acquire these two Rab proteins sequentially during infection and overexpression of Rab5 and Rab7 dominant negative mutants inhibited vacuole formation. Interestingly, CPh colocalized with the autophagy protein LC3 as early as 5 min after infection and this recruitment was dependent on the microorganism protein synthesis. Our results indicate that C. burnetii actively interacts with autophagosomes at early times after infection. Though interactions of whole pathogens with the autophagy pathway have been described, specific bacterial components modulating autophagy have not been identified so far. We have evidence of a link of autophagy with extracellular pathogens, like Vibrio cholerae, through a secreted molecule termed V. cholerae cytolysin (VCC).VCC-induced vacuoles colocalized with LC3, indicating the interaction with autophagic vesicles. In cells knock out for the autophagy protein Atg5, VCC failed to induce vacuolization and cell survival was dramatically impaired, indicating that autophagy also acts as a cellular defense pathway against a secreted bacterial toxin.