The mechanism of action of pepR, a viral-derived peptide, against Staphylococcus aureus biofilms
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10451/50777 |
Resumo: | © The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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The mechanism of action of pepR, a viral-derived peptide, against Staphylococcus aureus biofilms© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.comObjectives: To investigate the mechanism of action at the molecular level of pepR, a multifunctional peptide derived from the Dengue virus capsid protein, against Staphylococcus aureus biofilms. Methods: Biofilm mass, metabolic activity and viability were quantified using conventional microbiology techniques, while fluorescence imaging methods, including a real-time calcein release assay, were employed to investigate the kinetics of pepR activity at different biofilm depths. Results: Using flow cytometry-based assays, we showed that pepR is able to prevent staphylococcal biofilm formation due to a fast killing of planktonic bacteria, which in turn resulted from a peptide-induced increase in the permeability of the bacterial membranes. The activity of pepR against pre-formed biofilms was evaluated through the application of a quantitative live/dead confocal laser scanning microscopy (CLSM) assay. The results show that the bactericidal activity of pepR on pre-formed biofilms is dose and depth dependent. A CLSM-based assay of calcein release from biofilm-embedded bacteria was further developed to indirectly assess the diffusion and membrane permeabilization properties of pepR throughout the biofilm. A slower diffusion and delayed activity of the peptide at deeper layers of the biofilm were quantified. Conclusions: Overall, our results show that the activity of pepR on pre-formed biofilms is controlled by its diffusion along the biofilm layers, an effect that can be counteracted by an additional administration of peptide. Our study sheds new light on the antibiofilm mechanism of action of antimicrobial peptides, particularly the importance of their diffusion properties through the biofilm matrix on their activity.This work was supported by the Fundação para a Ciência e a Tecnologia (FCT)/Ministério da Ciência, Tecnologia e Ensino Superior (MCTES) (projects PTDC/QEQ-MED/4412/2014, FAPESP/20107/2014, SAICTPAC/0019/2015, PPBI-POCI-01-0145-FEDER-022122); by the Spanish Ministry of Economy and Competitiveness (MINECO) (grant AGL2014-5239-C2-2R); and by the Marie Skłodowska-Curie Research and Innovation Staff Exchange (grant H2020-MSCA-RISE-2014–644167). We also acknowledge project UID/BIM/50005/2019, funded by FCT/MCTES through Fundos do Orçamento de Estado. S. N. P., S. A. D., A. F. C. and D. M.-H. are the recipients of fellowships from the FCT (SFRH/BPD/92409/2013, PD/BD/114425/2016, PD/BD/136866/2018 and SFRH/BPD/91831/2012, respectively). A. S. V. and F. F. are FCT Researchers (IF/00803/2012 and IF/00386/2015, respectively).Oxford University PressRepositório da Universidade de LisboaPinto, SandraDias, SusanaCruz, Ana FMil-Homens, DalilaFernandes, FabioValle, JavierAndreu, DavidPrieto, ManuelCastanho, Miguel A. R. B.Coutinho, AnaVeiga, Ana Salomé2022-01-11T16:27:19Z20192019-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/50777engJ Antimicrob Chemother. 2019 Sep 1;74(9):2617-26250305-745310.1093/jac/dkz2231460-2091info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:55:07Zoai:repositorio.ul.pt:10451/50777Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:02:10.205362Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
The mechanism of action of pepR, a viral-derived peptide, against Staphylococcus aureus biofilms |
title |
The mechanism of action of pepR, a viral-derived peptide, against Staphylococcus aureus biofilms |
spellingShingle |
The mechanism of action of pepR, a viral-derived peptide, against Staphylococcus aureus biofilms Pinto, Sandra |
title_short |
The mechanism of action of pepR, a viral-derived peptide, against Staphylococcus aureus biofilms |
title_full |
The mechanism of action of pepR, a viral-derived peptide, against Staphylococcus aureus biofilms |
title_fullStr |
The mechanism of action of pepR, a viral-derived peptide, against Staphylococcus aureus biofilms |
title_full_unstemmed |
The mechanism of action of pepR, a viral-derived peptide, against Staphylococcus aureus biofilms |
title_sort |
The mechanism of action of pepR, a viral-derived peptide, against Staphylococcus aureus biofilms |
author |
Pinto, Sandra |
author_facet |
Pinto, Sandra Dias, Susana Cruz, Ana F Mil-Homens, Dalila Fernandes, Fabio Valle, Javier Andreu, David Prieto, Manuel Castanho, Miguel A. R. B. Coutinho, Ana Veiga, Ana Salomé |
author_role |
author |
author2 |
Dias, Susana Cruz, Ana F Mil-Homens, Dalila Fernandes, Fabio Valle, Javier Andreu, David Prieto, Manuel Castanho, Miguel A. R. B. Coutinho, Ana Veiga, Ana Salomé |
author2_role |
author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
dc.contributor.author.fl_str_mv |
Pinto, Sandra Dias, Susana Cruz, Ana F Mil-Homens, Dalila Fernandes, Fabio Valle, Javier Andreu, David Prieto, Manuel Castanho, Miguel A. R. B. Coutinho, Ana Veiga, Ana Salomé |
description |
© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019 2019-01-01T00:00:00Z 2022-01-11T16:27:19Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10451/50777 |
url |
http://hdl.handle.net/10451/50777 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
J Antimicrob Chemother. 2019 Sep 1;74(9):2617-2625 0305-7453 10.1093/jac/dkz223 1460-2091 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Oxford University Press |
publisher.none.fl_str_mv |
Oxford University Press |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799134571258707968 |