000144792 001__ 144792
000144792 005__ 20250923084420.0
000144792 0247_ $$2doi$$a10.1111/febs.17156
000144792 0248_ $$2sideral$$a139588
000144792 037__ $$aART-2024-139588
000144792 041__ $$aeng
000144792 100__ $$aFernández-Otal, Ángela
000144792 245__ $$aFunctional characterization of Fur from the strict anaerobe <i>Clostridioides difficile</i> provides insight into its redox-driven regulatory capacity
000144792 260__ $$c2024
000144792 5060_ $$aAccess copy available to the general public$$fUnrestricted
000144792 5203_ $$aClostridioides (formerly Clostridium) difficile 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 fur gene in C. difficile 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 C. difficile Fur and describe an additional oxidation sensing Fur‐mediated mechanism independent of iron, which affects Fur DNA‐binding. Using electrophoretic mobility shift assays, we show that Fur binding to the promoters of fur, feoA and fldX genes, identified as iron and Fur‐regulated genes in vivo, is specific and does not require co‐regulator metal under reducing conditions. Fur treatment with H2O2 produces dose‐dependent 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‐thioredoxin reductase/thioredoxin from Escherichia coli reduces inactive oligomerized C. difficile 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 C. difficile during infection.
000144792 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B18$$9info:eu-repo/grantAgreement/ES/DGA/E35-23R$$9info:eu-repo/grantAgreement/ES/FIS/PI11-02578$$9info:eu-repo/grantAgreement/ES/MEC/FPU2018-03619$$9info:eu-repo/grantAgreement/ES/MINECO/BFU2016-77671-P
000144792 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc$$uhttp://creativecommons.org/licenses/by-nc/3.0/es/
000144792 590__ $$a4.2$$b2024
000144792 592__ $$a2.212$$b2024
000144792 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b99 / 319 = 0.31$$c2024$$dQ2$$eT1
000144792 593__ $$aBiochemistry$$c2024$$dQ1
000144792 593__ $$aMolecular Biology$$c2024$$dQ1
000144792 593__ $$aCell Biology$$c2024$$dQ1
000144792 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000144792 700__ $$0(orcid)0000-0002-0474-255X$$aGuío, Jorge
000144792 700__ $$0(orcid)0000-0002-1960-2672$$aSarasa-Buisan, Cristina
000144792 700__ $$0(orcid)0000-0002-2742-3711$$aPeleato, M. Luisa
000144792 700__ $$0(orcid)0000-0001-8644-4574$$aFillat, María F.$$uUniversidad de Zaragoza
000144792 700__ $$0(orcid)0000-0001-5932-2889$$aLanas, Ángel$$uUniversidad de Zaragoza
000144792 700__ $$0(orcid)0000-0002-8181-2689$$aBes, M. Teresa$$uUniversidad de Zaragoza
000144792 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000144792 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000144792 773__ $$g291, 16 (2024), 3604-3627$$pFEBS J.$$tFEBS Journal$$x1742-464X
000144792 8564_ $$s4992084$$uhttps://zaguan.unizar.es/record/144792/files/texto_completo.pdf$$yVersión publicada
000144792 8564_ $$s2304736$$uhttps://zaguan.unizar.es/record/144792/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000144792 909CO $$ooai:zaguan.unizar.es:144792$$particulos$$pdriver
000144792 951__ $$a2025-09-22-14:35:20
000144792 980__ $$aARTICLE