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Virulence-linked mutations in rubredoxin reductase and glutaredoxin: impact on antibiotic susceptibility and phage therapy in Pseudomonas aeruginosa

dc.contributor.authorSá, Sara
dc.contributor.authorSilva, Carina
dc.contributor.authorDias, Maria Clara
dc.contributor.authorVeiga, Marlene
dc.contributor.authorLopes, Sofia
dc.contributor.authorFernandes, Ruben
dc.contributor.authorRocha, Ana Catarina
dc.contributor.authorPais, Patrick J.
dc.contributor.authorOliveira, Marco
dc.contributor.authorMendes, João
dc.contributor.authorNovais, Gonçalo
dc.contributor.authorLuís, Carla
dc.contributor.authorGestoso, Álvaro
dc.contributor.authorMacedo, José Mário
dc.contributor.authorMartins-Mendes, Daniela
dc.contributor.authorPereira, Ana Cláudia
dc.contributor.authorBaylina, Pilar
dc.date.accessioned2024-04-08T14:00:41Z
dc.date.available2024-04-08T14:00:41Z
dc.date.issued2023-10-31
dc.description.abstractPseudomonas aeruginosa (PAO1) is an opportunistic pathogen, lethal in immunocompromised individuals. The clinical management of PAO1 infections still depends deeply on antibiotic therapy. However, this therapy has been alarmingly overpowered by growing bacterial resistance mechanisms over the years. One of these bacterial mechanisms is quorum sensing (QS). QS is involved in the production of biofilm, rhamnolipids and pyocyanin, among other factors. The present study aimed to study the effect of the mutations in the genes of rubredoxin (Rub A1 and Rub A2) and glutaredoxin (GLRx) in the production of virulence traits and susceptibility of PAO1 to the antibiotic ciprofloxacin (CIP) and to infection by a phage cocktail. Rub A1, Rub A2, and GLRx showed a decrease in the expression of genes lasI, lasR, mvfR, and rpsL when compared to the wild type, PAO1. Rub A1 and Rub A2 also showed a decrease in the expression of the gene pqsA, while the mutant GLRx showed an increase of over 200% in expression compared to PAO1. The biofilm produced by the mutants Rub A1, Rub A2, and GLRx increased more than 1.5 times in comparison to PAO1, with statistical significance (p < 0.0001). In the viability assay, the mutant strain Rub A2 was the most susceptible to ciprofloxacin in both concentrations tested (p < 0.0001). The production of proteases increased in the mutant strains when compared to PAO1 (p < 0.05). However, there was a decrease in the production of rhamnolipids and pyocyanins in the mutant strains. In the phage assay, we could perceive a reduction in the growth of the mutant strains when compared to PAO1. Additionally, after the addition of the phages, all the strains showed susceptibility to the phage assay (p < 0.0001), observed in the decrease in the absorbance values. These results may highlight the relevance of the genes Rub A1, Rub A2, and GLRX in the proliferation and treatment of infections with PAO1. Overall, this study gives preliminary insights into how gene expression may be helpful in strategies to overcome antibiotic resistance.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationSá, S., Silva, C., Dias, M. C., Veiga, M., Lopes, S., Fernandes, R., Rocha, A. C., Pais, P. J., Oliveira, M., Mendes, J., Novais, G., Luís, C., Gestoso, Á., Macedo, J. M., Martins-Mendes, D., Pereira, A. C., & Baylina, P. (2023). Virulence-linked mutations in rubredoxin reductase and glutaredoxin: Impact on antibiotic susceptibility and phage therapy in Pseudomonas aeruginosa. Applied Sciences, 13(21), Artigo 21. https://doi.org/10.3390/app132111918pt_PT
dc.identifier.doi10.3390/app132111918pt_PT
dc.identifier.eissn2076-3417
dc.identifier.urihttp://hdl.handle.net/10400.22/25302
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relationPilar Baylina (PB) acknowledges on the behalf of the authors the support of Fundação para a Ciência e Tecnologia (FCT), Portuguese Government, under the Strategic Project Reference: UID/BIM/04293/2013. PB was also supported by FEDER/02/SAICT/2020/072560. Marco Oliveira was funded by LaBMI, grant number PORTIC/IPP4COVID/BI/2021/01. Gonçalo Novais was funded by LaBMI, grant number PORTIC/LABMI/BII/2021/01. Patrick J. Pais was funded by FCT, grant number 2021.09498.BD. Ana Catarina Rocha was funded by FCT, grant number 2021.06521.BD.pt_PT
dc.relation.publisherversionhttps://www.mdpi.com/2076-3417/13/21/11918pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectQuorum sensingpt_PT
dc.subjectOxidative stresspt_PT
dc.subjectAntibiotic stresspt_PT
dc.subjectBiofilm productionpt_PT
dc.subjectVirulencept_PT
dc.titleVirulence-linked mutations in rubredoxin reductase and glutaredoxin: impact on antibiotic susceptibility and phage therapy in Pseudomonas aeruginosapt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage15pt_PT
oaire.citation.startPage1pt_PT
oaire.citation.titleApplied Sciencespt_PT
oaire.citation.volume13(21)pt_PT
person.familyNameBAYLINA MACHADO
person.givenNamePILAR
person.identifier.ciencia-id1419-F23D-4920
person.identifier.orcid0000-0002-3740-862X
person.identifier.ridB-5134-2010
person.identifier.scopus-author-id56534079700
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicationb1482a24-d9d8-419d-af68-6df1a75afb3f
relation.isAuthorOfPublication.latestForDiscoveryb1482a24-d9d8-419d-af68-6df1a75afb3f

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