{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:50:39Z","timestamp":1782280239000,"version":"3.54.5"},"posted":{"date-parts":[[2024,9,5]]},"group-title":"Microbiology","reference-count":65,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T00:00:00Z","timestamp":1725494400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health, U.S.","award":["AI139425"],"award-info":[{"award-number":["AI139425"]}]},{"name":"National Institute of Health, U.S.","award":["AI083359"],"award-info":[{"award-number":["AI083359"]}]},{"name":"National Institute of Health, U.S.","award":["AI137031"],"award-info":[{"award-number":["AI137031"]}]},{"name":"National Institute of Health, U.S.","award":["AI168107"],"award-info":[{"award-number":["AI168107"]}]},{"DOI":"10.13039\/100000928","name":"Welch Foundation","doi-asserted-by":"crossref","award":["I-1704"],"award-info":[{"award-number":["I-1704"]}],"id":[{"id":"10.13039\/100000928","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,7,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  A central signal that marshals host defense against many infections is the lymphocyte-derived cytokine interferon-gamma (IFN\u03b3). The IFN\u03b3 receptor is expressed on most human cells, and its activation leads to the expression of antimicrobial proteins that execute diverse cell-autonomous immune programs. One such immune program consists of the sequential detection, ubiquitylation, and destruction of intracellular pathogens. Recently, the IFN\u03b3-inducible ubiquitin E3 ligase RNF213 was identified as a pivotal mediator of such a defense axis. RNF213 provides host protection against viral, bacterial, and protozoan pathogens. To establish infections, potentially susceptible intracellular pathogens must have evolved mechanisms that subdue RNF213-controlled cell-autonomous immunity. In support of this hypothesis, we demonstrate here that a causative agent of bacillary dysentery,\n                  <jats:italic>Shigella flexneri,<\/jats:italic>\n                  uses the type III secretion system (T3SS) effector IpaH1.4 to induce the degradation of RNF213.\n                  <jats:italic>S. flexneri<\/jats:italic>\n                  mutants lacking IpaH1.4 expression are bound and ubiquitylated by RNF213 in the cytosol of IFN\u03b3-primed host cells. Linear (M1-) and lysine-linked ubiquitylation of\n                  <jats:italic>S. flexneri<\/jats:italic>\n                  requires RNF213 but is independent of the linear ubiquitin chain assembly complex (LUBAC). We find that ubiquitylation of\n                  <jats:italic>S. flexneri<\/jats:italic>\n                  is insufficient to kill intracellular bacteria, suggesting that\n                  <jats:italic>S. flexneri<\/jats:italic>\n                  employs additional virulence factors to escape from host defenses that operate downstream from RNF213-driven ubiquitylation. In brief, this study identified the bacterial IpaH1.4 protein as an inhibitor of mammalian RNF213 and highlights evasion of RNF213-driven immunity as a characteristic of the human-tropic pathogen\n                  <jats:italic>Shigella<\/jats:italic>\n                  .\n                <\/jats:p>","DOI":"10.1101\/2024.09.05.611450","type":"posted-content","created":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T23:55:10Z","timestamp":1725580510000},"source":"Crossref","is-referenced-by-count":4,"title":["The\n                  <i>Shigella flexneri<\/i>\n                  effector IpaH1.4 facilitates RNF213 degradation and protects cytosolic bacteria against interferon-induced ubiquitylation"],"prefix":"10.64898","author":[{"given":"Luz","family":"Saavedra-Sanchez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary 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