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.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.identifier.citation Pinto SN, Dias SA, Cruz AF, Mil-Homens D, Fernandes F, Valle J et al. The mechanism of action of pepR, a viral-derived peptide, against Staphylococcus aureus biofilms. J Antimicrob Chemother. 2019;74(9):2617-25. DOI: 10.1093/jac/dkz223
  • dc.identifier.doi http://dx.doi.org/10.1093/jac/dkz223
  • dc.identifier.issn 0305-7453
  • dc.identifier.uri http://hdl.handle.net/10230/42434
  • dc.language.iso eng
  • dc.publisher Oxford University Press
  • dc.relation.ispartof Journal of Antimicrobial Chemotherapy. 2019;74(9):2617-25
  • 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 © 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.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
  • 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.title The mechanism of action of pepR, a viral-derived peptide, against Staphylococcus aureus biofilms
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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