{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T14:07:14Z","timestamp":1770473234074,"version":"3.49.0"},"reference-count":59,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"6","funder":[{"DOI":"10.13039\/501100013129","name":"Ministry of SMEs and Startups","doi-asserted-by":"crossref","award":["RS-2025-16068671"],"award-info":[{"award-number":["RS-2025-16068671"]}],"id":[{"id":"10.13039\/501100013129","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation, South Korea","doi-asserted-by":"crossref","award":["RS-2025-00556716"],"award-info":[{"award-number":["RS-2025-00556716"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation, South Korea","doi-asserted-by":"crossref","award":["RS-2023-00217123"],"award-info":[{"award-number":["RS-2023-00217123"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Multi-Ministerial Research Project, South Korea","award":["RS-2023-KH140699"],"award-info":[{"award-number":["RS-2023-KH140699"]}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,2,6]]},"abstract":"<jats:p>\n                    Enterohemorrhagic\n                    <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                    (EHEC) causes thrombotic microangiopathy, yet the red blood cell (RBC)\u2013centered mechanism has remained unclear. We identify the RTX-family hemolysin EhxA as the driver of RBC-mediated thrombogenesis. Deletion of\n                    <jats:italic toggle=\"yes\">ehxA<\/jats:italic>\n                    abolishes Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx, phosphatidylserine (PS) exposure, progression from discocyte to echinocyte to spherocyte, thrombin generation, RBC-endothelium adhesion, and RBC aggregation. Genetic complementation restores these readouts to wild type, and purified EhxA in bacteria-free assays recapitulates them while localizing to intact RBC membranes. By contrast, \u0394\n                    <jats:italic toggle=\"yes\">stx2<\/jats:italic>\n                    mutants do not elicit these RBC phenotypes, distinguishing this pathway from Shiga toxin\u2013dependent effects. Multiple regression quantifies the link between PS exposure, morphology, and procoagulant outputs. In rats, infection with wild type increased RBC remodeling and venous thrombosis, whereas infection with \u0394\n                    <jats:italic toggle=\"yes\">ehxA<\/jats:italic>\n                    did not. Together, the data define an EhxA-Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -PS pathway that drives RBC structural remodeling and procoagulant activation during EHEC infection and nominate RTX toxins as targets for preventing toxin-induced coagulopathies.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.ady8284","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T18:59:10Z","timestamp":1770404350000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["RTX-family toxin EhxA drives morphological remodeling and thrombogenesis in RBCs during enterohemorrhagic\n                    <i>Escherichia coli<\/i>\n                    infection"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9435-3434","authenticated-orcid":true,"given":"Sungbin","family":"Choi","sequence":"first","affiliation":[{"name":"College of Pharmacy Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan 15588, Republic of Korea."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3670-1896","authenticated-orcid":true,"given":"Hanjin","family":"Park","sequence":"additional","affiliation":[{"name":"College of Pharmacy Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan 15588, Republic of Korea."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0583-2116","authenticated-orcid":true,"given":"Ok-Nam","family":"Bae","sequence":"additional","affiliation":[{"name":"College of Pharmacy Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan 15588, Republic of Korea."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0504-2846","authenticated-orcid":true,"given":"Yiying","family":"Bian","sequence":"additional","affiliation":[{"name":"School of Public Health, China Medical University, Shenyang 110122, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5191-1304","authenticated-orcid":true,"given":"Hanhyeok","family":"Im","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Duke University, Durham 27713, NC, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0524-8278","authenticated-orcid":true,"given":"Han Young","family":"Chung","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1089\/fpd.2013.1704"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.01027-24"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1701.P11101"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2666-5247(22)00089-1"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2014.05.069"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.3168\/jds.S0022-0302(05)72706-5"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.02119-10"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01202-8"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(11)70165-7"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.medj.2023.09.002"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2023.10.017"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.EHEC-0024-2013"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7592"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12546"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0602359103"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.4161\/viru.26143"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2006050419"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2011.04251.x"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2108739"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2012.196"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2010.06.006"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-03-745349"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI122881"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-05-427856"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14360"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32599-0"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2008.615"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-00974-4"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1516594112"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.109.200956"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09583"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1252809"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0807044106"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2012.00081"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.64.11.4665-4672.1996"},{"key":"e_1_3_2_37_2","first-page":"1073","article-title":"Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome","volume":"365","author":"Tarr P. I.","year":"2005","unstructured":"P. I. Tarr, C. A. Gordon, W. L. Chandler, Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. Lancet 365, 1073\u20131086 (2005).","journal-title":"Lancet"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2008.610"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.186.16.5311-5320.2004"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.03.018"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro.2015.3"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-842X(99)01530-9"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-micro-090110-102943"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2010.00231.x"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-1895-4"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2017.06.001"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-023-01915-4"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1111\/febs.14606"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms14059848"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-025-07784-w"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4400946"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhazmat.2025.138303"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198303243081203"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.3.1055-1061.1995"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.04023-14"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01144.2009"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.953404"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1080"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1128\/genomeA.00821-14"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.611020"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.ady8284","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T19:00:14Z","timestamp":1770404414000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.ady8284"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,6]]},"references-count":59,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,2,6]]}},"alternative-id":["10.1126\/sciadv.ady8284"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.ady8284","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,6]]},"assertion":[{"value":"2025-05-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eady8284"}}