Disruption of the Nitric Oxide Reductase Operon via norD Deletion Does Not Affect Brucella abortus 2308W Virulence
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Date
2025-12-18
Authors
Rasheed, FaisalZúñiga Ripa, Amaia
Salvador Bescós, Miriam
Irshad, Hamid
Peña Villafruela, Raquel
Muñoz Álvaro, Pilar María
Miguel López, María Jesús de
Ali, Qurban
Conde Álvarez, Raquel
Khan, Saeed-ul-Hassan
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MDPI
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texto , revista , artículo , artículo originalAbstract
Brucella 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.
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Bibliographic citation
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., 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
AGROVOC subjects
BrucellaBrucella abortus
Respiración celular
Denitrificación
Sponsorship
Esta 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).