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How the pathogen modulates cellular functions to support its growth is poorly understood. The unfolded protein response (UPR) is a cytoprotective pathway that relieves endoplasmic reticulum (ER) stress by promoting ER-associated degradation (ERAD) of misfolded proteins. Here, we show that\n            <jats:named-content content-type=\"genus-species\">O. tsutsugamushi<\/jats:named-content>\n            invokes the UPR in the first 48 h and benefits from ER stress in an amino acid-dependent manner.\n            <jats:named-content content-type=\"genus-species\">O. tsutsugamushi<\/jats:named-content>\n            also impedes ERAD during this time period. By 72 h, ER stress is alleviated and ERAD proceeds unhindered. Sustained inhibition of ERAD using RNA interference results in an\n            <jats:named-content content-type=\"genus-species\">O. tsutsugamushi<\/jats:named-content>\n            growth defect at 72 h that can be rescued by amino acid supplementation. Thus,\n            <jats:named-content content-type=\"genus-species\">O. tsutsugamushi<\/jats:named-content>\n            temporally stalls ERAD until ERAD-derived amino acids are needed to support its growth. The\n            <jats:named-content content-type=\"genus-species\">O. tsutsugamushi<\/jats:named-content>\n            effector Ank4 is linked to this phenomenon. Ank4 interacts with Bat3, a eukaryotic chaperone that is essential for ERAD, and is transiently expressed by\n            <jats:named-content content-type=\"genus-species\">O. tsutsugamushi<\/jats:named-content>\n            during the infection period when it inhibits ERAD. Ectopically expressed Ank4 blocks ERAD to phenocopy\n            <jats:named-content content-type=\"genus-species\">O. tsutsugamushi<\/jats:named-content>\n            infection. Our data reveal a novel mechanism by which an obligate intracellular bacterial pathogen modulates ERAD to satisfy its nutritional virulence requirements.\n          <\/jats:p>","DOI":"10.1128\/iai.00596-17","type":"journal-article","created":{"date-parts":[[2017,11,6]],"date-time":"2017-11-06T16:25:11Z","timestamp":1509985511000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":31,"title":["Orientia tsutsugamushi Modulates Endoplasmic Reticulum-Associated Degradation To Benefit Its Growth"],"prefix":"10.1128","volume":"86","author":[{"given":"Kyle G.","family":"Rodino","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"VieBrock","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Virginia 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