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A long-chain flavodoxin protects pseudomonas aeruginosa from oxidative stress and host bacterial clearance

dc.citation.titlePLoS Genetics
dc.citation.volume10
dc.creatorMoyano, Alejandro José
dc.creatorTobares, Romina Alín
dc.creatorRizzi, Yanina S.
dc.creatorKrapp, Adriana R.
dc.creatorMondotte, Juan Alberto
dc.creatorBocco, José Luis
dc.creatorSaleh, Maria-Carla
dc.creatorCarrillo, Néstor
dc.creatorSmania, Andrea M.
dc.date.accessioned2024-05-14T21:36:37Z
dc.date.available2024-05-14T21:36:37Z
dc.date.issued2014-02-13
dc.description.abstractLong-chain flavodoxins, ubiquitous electron shuttles containing flavin mononucleotide (FMN) as prosthetic group, play an important protective role against reactive oxygen species (ROS) in various microorganisms. Pseudomonas aeruginosa is an opportunistic pathogen which frequently has to face ROS toxicity in the environment as well as within the host. We identified a single ORF, hereafter referred to as fldP (for flavodoxin from P. aeruginosa), displaying the highest similarity in length, sequence identity and predicted secondary structure with typical long-chain flavodoxins. The gene was cloned and expressed in Escherichia coli. The recombinant product (FldP) could bind FMN and exhibited flavodoxin activity in vitro. Expression of fldP in P. aeruginosa was induced by oxidative stress conditions through an OxyR-independent mechanism, and an fldP-null mutant accumulated higher intracellular ROS levels and exhibited decreased tolerance to H2O2 toxicity compared to wild-type siblings. The mutant phenotype could be complemented by expression of a cyanobacterial flavodoxin. Overexpression of FldP in a mutT-deficient P. aeruginosa strain decreased H2O2-induced cell death and the hypermutability caused by DNA oxidative damage. FldP contributed to the survival of P. aeruginosa within cultured mammalian macrophages and in infected Drosophila melanogaster, which led in turn to accelerated death of the flies. Interestingly, the fldP gene is present in some but not all P. aeruginosa strains, constituting a component of the P. aeruginosa accessory genome. It is located in a genomic island as part of a self-regulated polycistronic operon containing a suite of stress-associated genes. The collected results indicate that the fldP gene encodes a long-chain flavodoxin, which protects the cell from oxidative stress, thereby expanding the capabilities of P. aeruginosa to thrive in hostile environments.
dc.description.filFil: Moyano, Alejandro José. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica. Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC-CONICET); Argentina.
dc.description.filFil: Tobares, Romina Alín. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica. Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC-CONICET); Argentina.
dc.description.filFil: Rizzi, Yanina S. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica. Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC-CONICET); Argentina.
dc.description.filFil: Smania, Andrea M. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica. Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC-CONICET); Argentina.
dc.description.filFil: Krapp, Adriana R. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.
dc.description.filFil: Carrillo, Néstor. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.
dc.description.filFil: Mondotte, Juan Alberto. Institut Pasteur. Centre National de la Recherche Scientifique. Department of Virology. Viruses and RNA Interference; France.
dc.description.filFil: Saleh, Maria-Carla. Institut Pasteur. Centre National de la Recherche Scientifique. Department of Virology. Viruses and RNA Interference; France.
dc.description.filFil: Bocco, José Luis. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica. Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET); Argentina.
dc.description.sponsorshipAgencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación (Agencia I+D+i): PICT-2012–2088, PICT-2011-2621, PICT-2012-2284
dc.description.sponsorshipUniversidad Nacional de Córdoba. Secretaría de Ciencia y Tecnología (SeCyT): grant 05/C532
dc.description.sponsorshipInstitut Pasteur. LabEx IBEID
dc.description.sponsorshipAXA Research Fund
dc.description.sponsorshipConsejo Nacional de Investigaciones Científicas y Técnicas (CONICET)
dc.description.versionpeerreviewed
dc.format.extent1-15
dc.identifier.e-issn1553-7404
dc.identifier.issn1553-7390
dc.identifier.urihttps://hdl.handle.net/2133/27040
dc.language.isoen
dc.publisherPublic Library of Science (PLOS)
dc.relation.publisherversionhttps://doi.org/10.1371/journal.pgen.1004163
dc.relation.publisherversionhttps://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004163
dc.rightsopenAccess
dc.rights.holderMoyano, Alejandro José
dc.rights.holderTobares, Romina Alín
dc.rights.holderRizzi, Yanina S.
dc.rights.holderKrapp, Adriana R.
dc.rights.holderMondotte, Juan Alberto
dc.rights.holderBocco, José Luis
dc.rights.holderSaleh, Maria-Carla
dc.rights.holderCarrillo, Néstor
dc.rights.holderSmania, Andrea M.
dc.rights.holderUniversidad Nacional de Rosario
dc.rights.textAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectPseudomonas aeruginosa
dc.subjectFlavodoxin
dc.subjectOxidative stress
dc.subjectGenes, bacterial
dc.subjectReactive oxygen species
dc.titleA long-chain flavodoxin protects pseudomonas aeruginosa from oxidative stress and host bacterial clearance
dc.typearticulo
dc.type.collectionarticulo
dc.type.versionpublishedVersion

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