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Publication : Active escape of Orientia tsutsugamushi from cellular autophagy.

First Author  Ko Y Year  2013
Journal  Infect Immun Volume  81
Issue  2 Pages  552-9
PubMed ID  23230293 Mgi Jnum  J:192546
Mgi Id  MGI:5465362 Doi  10.1128/IAI.00861-12
Citation  Ko Y, et al. (2013) Active Escape of Orientia tsutsugamushi from Cellular Autophagy. Infect Immun 81(2):552-9
abstractText  Orientia tsutsugamushi, the causative agent of scrub typhus, is an obligate intracellular pathogen. After entry into host cells, the bacterium rapidly escapes from the endosomal pathway and replicates in the cytosol of eukaryotic host cells. Here we show that O. tsutsugamushi infection efficiently promotes cellular autophagy, a cell-autonomous defense mechanism of innate immunity. However, most of the internalized bacteria barely colocalized with the induced autophagosomes, even when stimulated with rapamycin, a chemical inducer of autophagy. Treatment of infected cells with tetracycline suppressed bacterial evasion from autophagy and facilitated O. tsutsugamushi targeting to autophagosomes, suggesting that the intracellular pathogen may be equipped with a bacterial factor or factors that block autophagic recognition. Finally, we also found that chemical modulators of cellular autophagy or genetic knockout of the atg3 gene does not significantly affect the intracellular growth of O. tsutsugamushi in vitro. These results suggest that O. tsutsugamushi has evolved to block autophagic microbicidal defense by evading autophagic recognition even though it activates the autophagy pathway during the early phase of infection.
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