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Defense arsenal of the strict anaerobe Clostridioides difficile against reactive oxygen species encountered during its infection cycle

2025-03-20Artigo científico Acesso aberto
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dc.contributor.authorLotoux, Aurélie
dc.contributor.authorCaulat, Léo
dc.contributor.authorAlves, Catarina Martins
dc.contributor.authorFeliciano, Carolina Alves
dc.contributor.authorMorvan, Claire
dc.contributor.authorFolgosa, Filipe
dc.contributor.authorMartin-Verstraete, Isabelle
dc.contributor.institutionInstituto de Tecnologia Química e Biológica António Xavier (ITQB)
dc.contributor.pblAmerican Society for Microbiology
dc.date.accessioned2025-10-02T22:01:08Z
dc.date.available2025-10-02T22:01:08Z
dc.date.issued2025-03-20
dc.descriptionFunding Information: We thank Angela Guillem Vernia for its help with experiments and Bruno Dupuy, Miguel Teixeira, and Cyril Anjou for helpful discussions. This work was supported by the ANR Difox (ANR-22-CE15-0026-01) and by the Institut Universitaire de France for Isabelle Martin-Verstraete. This work was financially supported by the Portuguese Funda\u00E7\u00E3o para a Ci\u00EAncia e Tecnologia (FCT), PTDC/ BIA-BQM/0562/2020 project, MOSTMICRO-ITQB R&D Unit (references UIDB/04612/2020 and UIDP/04612/2020), and LS4FUTURE Associated Laboratory (LA/P/0087/2020). C.M.A. is recipient of FCT PhD grant UI/BD/154601/2022. Portuguese FCT PTDC/BIA-BQM/0562/2020 Filipe Folgosa LS4Future associated Laboratory LA/P/0087/2020 Filipe Folgosa Portuguese FCT UIDB/04612/2020 Filipe Folgosa Portuguese FCT UIDP/04612/2020 Filipe Folgosa Portuguese FCT UI/BD/154601/2022 Catarina Martins Alves Publisher Copyright: Copyright © 2025 Lotoux et al.
dc.description.abstractClostridioides difficile, a strict anaerobe, is the major cause of antibiotic-associated diarrhea. This enteropathogen must adapt to oxidative stress mediated by reactive oxygen species (ROS), notably those released by the neutrophils and macrophages recruited to the site of infection or those endogenously produced upon high oxygen (O2) exposure. C. difficile uses a superoxide reductase, Sor, and several peroxidases to detoxify ROS. We showed that Sor has a superoxide reductase activity in vitro and protects the bacterium from exposure to menadione, a superoxide donor. After confirming the peroxidase activity of the rubrerythrin, Rbr, we showed that this enzyme together with the peroxiredoxin, Bcp, plays a central role in the detoxification of H2O2 and promotes the survival of C. difficile in the presence of not only H2O2 but also air or 4% O2. Under high O2 concentrations encountered in the gastrointestinal tract, the bacterium generated endogenous H2O2. The two O2 reductases, RevRbr2 and FdpF, have also a peroxidase activity and participate in H2O2 resistance. The CD0828 gene, which also contributes to H2O2 protection, forms an operon with rbr, sor, and perR encoding a H2O2-sensing repressor. The expression of the genes encoding the ROS reductases and the CD0828 protein was induced upon exposure to either H2O2 or air. We showed that the induction of the rbr operon is mediated not only by PerR but also by OseR, a recently identified O2-responsive regulator of C.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent2220005
dc.identifier.doi10.1128/mbio.03753-24
dc.identifier.issn2161-2129
dc.identifier.otherPURE: 118418330
dc.identifier.otherPURE UUID: 9d7c5061-97b7-4fdf-906d-45a7850e8c83
dc.identifier.otherScopus: 105002783661
dc.identifier.otherPubMed: 40111048
dc.identifier.urihttp://hdl.handle.net/10362/188916
dc.identifier.urlhttps://www.scopus.com/pages/publications/105002783661
dc.language.isoeng
dc.peerreviewedyes
dc.subjectperoxidase
dc.subjectPerR
dc.subjectrubrerythrin
dc.subjectSigma B
dc.subjectSpx
dc.subjectstress response
dc.subjectsuperoxide reductase
dc.subjectMicrobiology
dc.subjectVirology
dc.subjectSDG 3 - Good Health and Well-being
dc.titleDefense arsenal of the strict anaerobe Clostridioides difficile against reactive oxygen species encountered during its infection cycleen
dc.typejournal article
degois.publication.issue4
degois.publication.titlemBio
degois.publication.volume16
dspace.entity.typePublication
rcaap.rightsopenAccess

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