The mechanism of action of pepR, a viral-derived peptide, against Staphylococcus aureus biofilms

Detalhes bibliográficos
Autor(a) principal: Pinto, Sandra
Data de Publicação: 2019
Outros Autores: 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
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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spelling 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
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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
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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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