Disruption of the Nitric Oxide Reductase Operon via norD Deletion Does Not Affect Brucella abortus 2308W Virulence

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dc.contributor.authorRasheed, Faisal
dc.contributor.authorZúñiga Ripa, Amaia
dc.contributor.authorSalvador Bescós, Miriam
dc.contributor.authorIrshad, Hamid
dc.contributor.authorPeña Villafruela, Raquel
dc.contributor.authorMuñoz Álvaro, Pilar María
dc.contributor.authorMiguel López, María Jesús de
dc.contributor.authorAli, Qurban
dc.contributor.authorConde Álvarez, Raquel
dc.contributor.authorKhan, Saeed-ul-Hassan
dc.contributor.orcidMuñoz Álvaro, Pilar María [0000-0002-7970-4929]
dc.date.accessioned2025-12-19T12:48:14Z
dc.date.available2025-12-19T12:48:14Z
dc.date.issued2025-12-18
dc.date.updated2025-12-19T09:22:53Z
dc.description.abstractBrucella are intracellular pathogens that use flexible respiratory strategies to adapt to oxygen-limited conditions. The nor operon encodes components of nitric oxide reductase (Nor), which are involved in denitrification and nitric oxide (NO) detoxification. In this study, the role of the norD gene in nitrate-dependent respiration, resistance to nitrosative stress, and intracellular persistence in B. abortus was evaluated. A non-polar ΔnorD mutant was generated in strain 2308W and its survival and growth under aerobic and anaerobic conditions, with and without nitrate, as well as its tolerance to NO donors, were analyzed. In addition, its behavior was evaluated in activated and non-activated murine RAW264.7 and human THP-1 macrophages and in a murine infection model. The deletion of norD did not affect viability or growth under any of the conditions tested, nor did it alter resistance to NO in vitro or within activated macrophages. Furthermore, the mutant showed virulence comparable to the wild-type strain in BALB/c mice. These results contrast with those described for other Brucella species, suggesting that norD is dispensable in B. abortus 2308W virulence and that in the Brucella genus, there are species-specific differences in the role of the nor operon during infection.
dc.description.peerreviewedSi
dc.description.sponsorshipEsta investigación ha sido financiada por MCIN/AEI/10.1303910.13039/501100011033 y FEDER, UE en el marco de los proyectos PID2023-146797OB-C31, PID2023-146797OB-C32, PID2019-107601RB-C31 y PID2019-107601RA-C32. La estancia de F.R. en la Universidad de Navarra fue financiada por la Comisión de Educación Superior de Pakistán. R.P.-V. es beneficiario de la beca de doctorado financiada por PREP2023-000737. El trabajo de P.M.M. y M.J.d.M. (CITA) también contó con el apoyo del Gobierno de Aragón (Grupo de Investigación A21_23R).
dc.identifier.citationRasheed, F., Zúñiga-Ripa, A., Salvador-Bescós, M., Irshad, H., Peña-Villafruela, R., Muñoz, P. M., Miguel, M. J. de, Ali, Q., Conde-Álvarez, R., Khan, S.-H., Rasheed, F., Zúñiga-Ripa, A., Salvador-Bescós, M., Irshad, H., Peña-Villafruela, R., Muñoz, P. M., Miguel, M. J. de, Ali, Q., Conde-Álvarez, R., & Khan, S.-H. (2025). Disruption of the Nitric Oxide Reductase Operon via norD Deletion Does Not Affect Brucella abortus 2308W Virulence. Microorganisms, 13(12). https://doi.org/10.3390/microorganisms13122875
dc.identifier.doi10.3390/microorganisms13122875
dc.identifier.issn2076-2607
dc.identifier.urihttps://doi.org/10.3390/microorganisms13122875
dc.identifier.urihttps://hdl.handle.net/10532/8061
dc.language.isoen
dc.publisherMDPI
dc.relationinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2023-146797OB-C32/ES/AVANZANDO EN VACUNAS SEGURAS CONTRA LA BRUCELOSIS OVINA: EFICACIA DE CANDIDATOS VACUNALES MEJORADOS DE B. MELITENSIS Y B. OVIS Y MODELOS IN VITRO INNOVADORES/BruVac-Cell
dc.relationinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-107601RB-C31/ES/Brucellosis ovina: vacunas seguras y estrategias DIVA frente a B. melitensis y B. ovis/Bru-DIsafe
dc.relation.citaSi
dc.relation.publisherversionhttps://doi.org/10.3390/microorganisms13122875
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Spainen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
dc.subject.agrovocBrucella
dc.subject.agrovocBrucella abortus
dc.subject.agrovocRespiración celular
dc.subject.agrovocDenitrificación
dc.subject.sdgHambre cero
dc.subject.sdgSalud y bienestar
dc.titleDisruption of the Nitric Oxide Reductase Operon via norD Deletion Does Not Affect Brucella abortus 2308W Virulence
dc.typetexto
dc.typerevista
dc.typeartículo
dc.typeartículo original
dc.type.hasVersionversión publicada

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