title: Active escape of Orientia tsutsugamushi from cellular autophagy.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, Seoul National University College of Medicine, Jongno-Gu, Seoul, Republic of Korea.
authors.forename: Youngho
authors.initials: Y
authors.lastname: Ko
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Choi
authors.forename: Na-Young
authors.initials: NY
authors.lastname: Ha
authors.forename: Ik-Sang
authors.initials: IS
authors.lastname: Kim
authors.forename: Nam-Hyuk
authors.initials: NH
authors.lastname: Cho
authors.forename: Myung-Sik
authors.initials: MS
authors.lastname: Choi
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D012285:Orientia tsutsugamushi / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D012612:Scrub Typhus / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents