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

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dc.contributor.author Pinto, Sandra N.
dc.contributor.author Dias, Susana A.
dc.contributor.author Cruz, Ana F.
dc.contributor.author Mil-Homens, Dalila
dc.contributor.author Fernandes, Fabio
dc.contributor.author Valle, Javier
dc.contributor.author Andreu Martínez, David
dc.contributor.author Prieto, Manuel
dc.contributor.author Castanho, Miguel A.R.B.
dc.contributor.author Coutinho, Ana
dc.contributor.author Salomé Veiga, Ana
dc.date.accessioned 2019-10-11T11:07:37Z
dc.date.available 2019-10-11T11:07:37Z
dc.date.issued 2019
dc.identifier.citation Pinto SN, Dias SA, Cruz AF, Mil-Homens D, Fernandes F, Valle J, Andreu D, Prieto M, Castanho MARB, Coutinho A, Veiga AS. The mechanism of action of pepR, a viral-derived peptide, against Staphylococcus aureus biofilms. J Antimicrob Chemother. 2019; 74(9):2617-2625. DOI 10.1093/jac/dkz223
dc.identifier.issn 0305-7453
dc.identifier.uri http://hdl.handle.net/10230/42434
dc.description.abstract Objectives: 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.
dc.description.sponsorship 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).
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Oxford University Press
dc.relation.ispartof J Antimicrob Chemother. 2019; 74(9):2617-2625
dc.rights © 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
dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
dc.title The mechanism of action of pepR, a viral-derived peptide, against Staphylococcus aureus biofilms
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1093/jac/dkz223
dc.subject.keyword Staphylococcus aureus
dc.subject.keyword Diffusion
dc.subject.keyword Biofilms
dc.subject.keyword Tissue membrane
dc.subject.keyword Peptides
dc.subject.keyword Bacteria
dc.subject.keyword Pharmacokinetics
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/AGL2014-5239-C2-2R
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/644167
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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