Publicação
Virulence-linked mutations in rubredoxin reductase and glutaredoxin: impact on antibiotic susceptibility and phage therapy in Pseudomonas aeruginosa
| Resumo: | Pseudomonas 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. |
|---|---|
| Autores principais: | Sá, Sara |
| Outros Autores: | Silva, Carina; Dias, Maria Clara; Veiga, Marlene; Lopes, Sofia; Fernandes, Ruben; Rocha, Ana Catarina; Pais, Patrick J.; Oliveira, Marco; Mendes, João; Novais, Gonçalo; Luís, Carla; Gestoso, Álvaro; Macedo, José Mário; Martins-Mendes, Daniela; Pereira, Ana Cláudia; Baylina, Pilar |
| Assunto: | Quorum sensing Oxidative stress Antibiotic stress Biofilm production Virulence |
| Ano: | 2023 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Instituto Politécnico do Porto |
| Idioma: | inglês |
| Origem: | Repositório Científico do Instituto Politécnico do Porto |
| _version_ | 1868786539629117440 |
|---|---|
| author | Sá, Sara |
| author2 | Silva, Carina Dias, Maria Clara Veiga, Marlene Lopes, Sofia Fernandes, Ruben Rocha, Ana Catarina Pais, Patrick J. Oliveira, Marco Mendes, João Novais, Gonçalo Luís, Carla Gestoso, Álvaro Macedo, José Mário Martins-Mendes, Daniela Pereira, Ana Cláudia Baylina, Pilar |
| author2_role | author author author author author author author author author author author author author author author author |
| author_facet | Sá, Sara Silva, Carina Dias, Maria Clara Veiga, Marlene Lopes, Sofia Fernandes, Ruben Rocha, Ana Catarina Pais, Patrick J. Oliveira, Marco Mendes, João Novais, Gonçalo Luís, Carla Gestoso, Álvaro Macedo, José Mário Martins-Mendes, Daniela Pereira, Ana Cláudia Baylina, Pilar |
| author_role | author |
| contributor_name_str_mv | REPOSITÓRIO P.PORTO |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Sá, Sara\"},{\"Person.name\":\"Silva, Carina\"},{\"Person.name\":\"Dias, Maria Clara\"},{\"Person.name\":\"Veiga, Marlene\"},{\"Person.name\":\"Lopes, Sofia\"},{\"Person.name\":\"Fernandes, Ruben\"},{\"Person.name\":\"Rocha, Ana Catarina\"},{\"Person.name\":\"Pais, Patrick J.\"},{\"Person.name\":\"Oliveira, Marco\"},{\"Person.name\":\"Mendes, João\"},{\"Person.name\":\"Novais, Gonçalo\"},{\"Person.name\":\"Luís, Carla\"},{\"Person.name\":\"Gestoso, Álvaro\"},{\"Person.name\":\"Macedo, José Mário\"},{\"Person.name\":\"Martins-Mendes, Daniela\"},{\"Person.name\":\"Pereira, Ana Cláudia\"},{\"Person.name\":\"Baylina, Pilar\",\"Person.identifier.orcid\":\"0000-0002-3740-862X\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | REPOSITÓRIO P.PORTO |
| datacite.creators.creator.creatorName.fl_str_mv | Sá, Sara Silva, Carina Dias, Maria Clara Veiga, Marlene Lopes, Sofia Fernandes, Ruben Rocha, Ana Catarina Pais, Patrick J. Oliveira, Marco Mendes, João Novais, Gonçalo Luís, Carla Gestoso, Álvaro Macedo, José Mário Martins-Mendes, Daniela Pereira, Ana Cláudia Baylina, Pilar |
| datacite.date.Accepted.fl_str_mv | 2023-10-31T00:00:00Z |
| datacite.date.available.fl_str_mv | 2024-04-08T14:00:41Z |
| datacite.date.embargoed.fl_str_mv | 2024-04-08T14:00:41Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | Quorum sensing Oxidative stress Antibiotic stress Biofilm production Virulence |
| datacite.titles.title.fl_str_mv | Virulence-linked mutations in rubredoxin reductase and glutaredoxin: impact on antibiotic susceptibility and phage therapy in Pseudomonas aeruginosa |
| dc.contributor.none.fl_str_mv | REPOSITÓRIO P.PORTO |
| dc.creator.none.fl_str_mv | Sá, Sara Silva, Carina Dias, Maria Clara Veiga, Marlene Lopes, Sofia Fernandes, Ruben Rocha, Ana Catarina Pais, Patrick J. Oliveira, Marco Mendes, João Novais, Gonçalo Luís, Carla Gestoso, Álvaro Macedo, José Mário Martins-Mendes, Daniela Pereira, Ana Cláudia Baylina, Pilar |
| dc.date.Accepted.fl_str_mv | 2023-10-31T00:00:00Z |
| dc.date.available.fl_str_mv | 2024-04-08T14:00:41Z |
| dc.date.embargoed.fl_str_mv | 2024-04-08T14:00:41Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10400.22/25302 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | MDPI |
| dc.rights.cclincense.fl_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | Quorum sensing Oxidative stress Antibiotic stress Biofilm production Virulence |
| dc.title.fl_str_mv | Virulence-linked mutations in rubredoxin reductase and glutaredoxin: impact on antibiotic susceptibility and phage therapy in Pseudomonas aeruginosa |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | Pseudomonas 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. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://recipp.ipp.pt/bitstreams/9543b675-89a4-4bfa-aa04-04c95d4999bc/download |
| id | recipp_c818bd22ba2bb65cc0dc375b5d3cd577 |
| identifier.url.fl_str_mv | http://hdl.handle.net/10400.22/25302 |
| instacron_str | recipp |
| institution | Instituto Politécnico do Porto |
| instname_str | Instituto Politécnico do Porto |
| language | eng |
| network_acronym_str | recipp |
| network_name_str | Repositório Científico do Instituto Politécnico do Porto |
| oai_identifier_str | oai:recipp.ipp.pt:10400.22/25302 |
| organization_str_mv | urn:organizationAcronym:recipp |
| person_str_mv | Sá, Sara Silva, Carina Dias, Maria Clara Veiga, Marlene Lopes, Sofia Fernandes, Ruben Rocha, Ana Catarina Pais, Patrick J. Oliveira, Marco Mendes, João Novais, Gonçalo Luís, Carla Gestoso, Álvaro Macedo, José Mário Martins-Mendes, Daniela Pereira, Ana Cláudia Baylina, Pilar Baylina, Pilar https://www.ciencia-id.pt/1419-F23D-4920 1419-F23D-4920 http://orcid.org/0000-0002-3740-862X 0000-0002-3740-862X |
| publishDate | 2023 |
| publisher.none.fl_str_mv | MDPI |
| reponame_str | Repositório Científico do Instituto Politécnico do Porto |
| repository_id_str | urn:repositoryAcronym:recipp |
| service_str_mv | urn:repositoryAcronym:recipp |
| spelling | engMDPIpt_PTPseudomonas 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.application/pdfpt_PTVirulence-linked mutations in rubredoxin reductase and glutaredoxin: impact on antibiotic susceptibility and phage therapy in Pseudomonas aeruginosaSá, SaraSilva, CarinaDias, Maria ClaraVeiga, MarleneLopes, SofiaFernandes, RubenRocha, Ana CatarinaPais, Patrick J.Oliveira, MarcoMendes, JoãoNovais, GonçaloLuís, CarlaGestoso, ÁlvaroMacedo, José MárioMartins-Mendes, DanielaPereira, Ana CláudiaPersonalBaylina, PilarDSpacehttp://dspace.org/items/b1482a24-d9d8-419d-af68-6df1a75afb3fDSpacehttp://dspace.org/items/b1482a24-d9d8-419d-af68-6df1a75afb3fBAYLINA MACHADOPILARCiência IDhttps://www.ciencia-id.pt1419-F23D-4920ORCIDhttp://orcid.org0000-0002-3740-862XResearcher IDhttps://www.researcherid.comB-5134-2010Scopus Author IDhttps://www.scopus.com56534079700HostingInstitutionOrganizationalREPOSITÓRIO P.PORTOe-mailmailto:recipp@sc.ipp.ptrecipp@sc.ipp.ptDOIIsPartOf10.3390/app1321119182024-04-08T14:00:41Z2023-10-312023-10-31T00:00:00ZHandlehttp://hdl.handle.net/10400.22/25302http://purl.org/coar/access_right/c_abf2open accessQuorum sensingOxidative stressAntibiotic stressBiofilm productionVirulence2552067 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal article2023-10-31http://creativecommons.org/licenses/by/4.0/http://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://recipp.ipp.pt/bitstreams/9543b675-89a4-4bfa-aa04-04c95d4999bc/downloadApplied Sciences13(21)115 |
| spellingShingle | Virulence-linked mutations in rubredoxin reductase and glutaredoxin: impact on antibiotic susceptibility and phage therapy in Pseudomonas aeruginosa Sá, Sara Quorum sensing Oxidative stress Antibiotic stress Biofilm production Virulence |
| status | SINGLETON |
| subject.fl_str_mv | Quorum sensing Oxidative stress Antibiotic stress Biofilm production Virulence |
| title | Virulence-linked mutations in rubredoxin reductase and glutaredoxin: impact on antibiotic susceptibility and phage therapy in Pseudomonas aeruginosa |
| title_full | Virulence-linked mutations in rubredoxin reductase and glutaredoxin: impact on antibiotic susceptibility and phage therapy in Pseudomonas aeruginosa |
| title_fullStr | Virulence-linked mutations in rubredoxin reductase and glutaredoxin: impact on antibiotic susceptibility and phage therapy in Pseudomonas aeruginosa |
| title_full_unstemmed | Virulence-linked mutations in rubredoxin reductase and glutaredoxin: impact on antibiotic susceptibility and phage therapy in Pseudomonas aeruginosa |
| title_short | Virulence-linked mutations in rubredoxin reductase and glutaredoxin: impact on antibiotic susceptibility and phage therapy in Pseudomonas aeruginosa |
| title_sort | Virulence-linked mutations in rubredoxin reductase and glutaredoxin: impact on antibiotic susceptibility and phage therapy in Pseudomonas aeruginosa |
| topic | Quorum sensing Oxidative stress Antibiotic stress Biofilm production Virulence |
| topic_facet | Quorum sensing Oxidative stress Antibiotic stress Biofilm production Virulence |
| url | http://hdl.handle.net/10400.22/25302 |
| visible | 1 |