{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T10:54:20Z","timestamp":1780397660716,"version":"3.54.1"},"reference-count":69,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2024,5,22]],"date-time":"2024-05-22T00:00:00Z","timestamp":1716336000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["FIS: PI11\/02578"],"award-info":[{"award-number":["FIS: PI11\/02578"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["FI12\/00482"],"award-info":[{"award-number":["FI12\/00482"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["BFU2016\u201077671\u2010P"],"award-info":[{"award-number":["BFU2016\u201077671\u2010P"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:p><jats:italic>Clostridioides<\/jats:italic> (formerly <jats:italic>Clostridium<\/jats:italic>) <jats:italic>difficile<\/jats:italic> is a leading cause of infectious diarrhea associated with antibiotic therapy. The ability of this anaerobic pathogen to acquire enough iron to proliferate under iron limitation conditions imposed by the host largely determines its pathogenicity. However, since high intracellular iron catalyzes formation of deleterious reactive hydroxyl radicals, iron uptake is tightly regulated at the transcriptional level by the ferric uptake regulator Fur. Several studies relate lacking a functional <jats:italic>fur<\/jats:italic> gene in <jats:italic>C.\u2009difficile<\/jats:italic> cells to higher oxidative stress sensitivity, colonization defect and less toxigenicity, although Fur does not appear to directly regulate either oxidative stress response genes or pathogenesis genes. In this work, we report the functional characterization of <jats:italic>C.\u2009difficile<\/jats:italic> Fur and describe an additional oxidation sensing Fur\u2010mediated mechanism independent of iron, which affects Fur DNA\u2010binding. Using electrophoretic mobility shift assays, we show that Fur binding to the promoters of <jats:italic>fur<\/jats:italic>, <jats:italic>feoA<\/jats:italic> and <jats:italic>fldX<\/jats:italic> genes, identified as iron and Fur\u2010regulated genes <jats:italic>in vivo<\/jats:italic>, is specific and does not require co\u2010regulator metal under reducing conditions. Fur treatment with H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> produces dose\u2010dependent soluble high molecular weight species unable to bind to target promoters. Moreover, Fur oligomers are dithiotreitol sensitive, highlighting the importance of some interchain disulfide bond(s) for Fur oligomerization, and hence for activity. Additionally, the physiological electron transport chain NADPH\u2010thioredoxin reductase\/thioredoxin from <jats:italic>Escherichia coli<\/jats:italic> reduces inactive oligomerized <jats:italic>C.\u2009difficile<\/jats:italic> Fur that recovers activity. In conjunction with available transcriptomic data, these results suggest a previously underappreciated complexity in the control of some members of the Fur regulon that is based on Fur redox properties and might be fundamental for the adaptive response of <jats:italic>C.\u2009difficile<\/jats:italic> during infection.<\/jats:p>","DOI":"10.1111\/febs.17156","type":"journal-article","created":{"date-parts":[[2024,5,22]],"date-time":"2024-05-22T09:44:56Z","timestamp":1716371096000},"page":"3604-3627","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Functional characterization of Fur from the strict anaerobe <i>Clostridioides difficile<\/i> provides insight into its redox\u2010driven regulatory capacity"],"prefix":"10.1111","volume":"291","author":[{"given":"\u00c1ngela","family":"Fern\u00e1ndez\u2010Otal","sequence":"first","affiliation":[{"name":"Department of Biochemistry &amp; Molecular and Cellular Biology University of Zaragoza  Spain"},{"name":"Institute for Biocomputation and Physics of Complex Systems (BIFI), Mariano Esquillor (Edif. I+D)  Zaragoza Spain"},{"name":"Aragon Institute for Health Research (IIS Arag\u00f3n)  Zaragoza Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Gu\u00edo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry &amp; Molecular and Cellular Biology University of Zaragoza  Spain"},{"name":"Institute for Biocomputation and Physics of Complex Systems (BIFI), Mariano Esquillor (Edif. I+D)  Zaragoza Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Sarasa\u2010Buisan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry &amp; Molecular and Cellular Biology University of Zaragoza  Spain"},{"name":"Institute for Biocomputation and Physics of Complex Systems (BIFI), Mariano Esquillor (Edif. I+D)  Zaragoza Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Luisa","family":"Peleato","sequence":"additional","affiliation":[{"name":"Department of Biochemistry &amp; Molecular and Cellular Biology University of Zaragoza  Spain"},{"name":"Institute for Biocomputation and Physics of Complex Systems (BIFI), Mariano Esquillor (Edif. I+D)  Zaragoza Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda F.","family":"Fillat","sequence":"additional","affiliation":[{"name":"Department of Biochemistry &amp; Molecular and Cellular Biology University of Zaragoza  Spain"},{"name":"Institute for Biocomputation and Physics of Complex Systems (BIFI), Mariano Esquillor (Edif. I+D)  Zaragoza Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1ngel","family":"Lanas","sequence":"additional","affiliation":[{"name":"Aragon Institute for Health Research (IIS Arag\u00f3n)  Zaragoza Spain"},{"name":"Digestive Diseases Service University Clinic Hospital Lozano Blesa  Zaragoza Spain"},{"name":"CIBERehd  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8181-2689","authenticated-orcid":false,"given":"M. Teresa","family":"Bes","sequence":"additional","affiliation":[{"name":"Department of Biochemistry &amp; Molecular and Cellular Biology University of Zaragoza  Spain"},{"name":"Institute for Biocomputation and Physics of Complex Systems (BIFI), Mariano Esquillor (Edif. I+D)  Zaragoza Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,22]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anaerobe.2016.06.008"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.161.4.525"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2006.01580.x"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/19485565.2016.1172957"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.02250-16"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0082622"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02350-14"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00515-13"},{"key":"e_1_2_10_10_1","doi-asserted-by":"crossref","unstructured":"DeshpandeA OlaitanAO McKelveyAM RutherfordJT&HurdleJG(2022)The ferrous iron transporter FeoB1 is essential forClostridioides difficiletoxin production and pathogenesis in mice.bioRxiv10.1101\/2022.03.03.482942[PREPRINT]","DOI":"10.1101\/2022.03.03.482942"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/femspd\/fty009"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2013.00059"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1369-5274(00)00184-3"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5910"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2015.03.024"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0111168"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/pcp\/pcq148"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku123"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0151384"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.181.20.6223-6229.1999"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-4274(95)03532-X"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.182.21.5948-5953.2000"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/jz301689b"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2014.01.029"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2010.07517.x"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1118321109"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2014.6175"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00098-15"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.03183"},{"key":"e_1_2_10_30_1","article-title":"Clostridioides difficile strain\u2010dependent and strain\u2010independent adaptations to a microaerobic environment","volume":"7","author":"Weiss A","year":"2021","journal-title":"Microb Genom"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0053757"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2016-312388.43"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.1996.tb08345.x"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00337769"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.procbio.2009.09.019"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2012.08606.x"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj20020135"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1999.3091"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2003.03337.x"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8642"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.071365-0"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(85)90409-9"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001677"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1021\/ic401072d"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi9004396"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2003.03757.x"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.2006\/000620-0"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1039\/C8MT00097B"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1104\/pp.73.3.724"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1128\/jb.169.6.2624-2630.1987"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genet-102108-134201"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10060913"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molp.2016.06.019"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2008.11.046"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00040.2012"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.07.009"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.27581-0"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.187.11.3687-3692.2005"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01026-13"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.27404-0"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.74.1.602-614.2006"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.187.18.6596-6598.2005"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.02014"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anaerobe.2018.05.018"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi982788s"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.H120.016190"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA120.014814"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10534-022-00390-9"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2009.01.055"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(59)90090-6"}],"container-title":["The FEBS Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/febs.17156","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T15:12:01Z","timestamp":1723648321000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1111\/febs.17156"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,22]]},"references-count":69,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["10.1111\/febs.17156"],"URL":"https:\/\/doi.org\/10.1111\/febs.17156","archive":["Portico"],"relation":{},"ISSN":["1742-464X","1742-4658"],"issn-type":[{"value":"1742-464X","type":"print"},{"value":"1742-4658","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,22]]},"assertion":[{"value":"2023-12-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}