A designed cyclic analogue of gomesin has potent activity against Staphylococcus aureus biofilms
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2022 |
| 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/10451/54640 |
Resumo: | © The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https:// 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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A designed cyclic analogue of gomesin has potent activity against Staphylococcus aureus biofilms© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https:// 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.comBackground: Infections caused by bacterial biofilms are very difficult to treat. The use of currently approved antibiotics even at high dosages often fails, making the treatment of these infections very challenging. Novel antimicrobial agents that use distinct mechanisms of action are urgently needed. Objectives: To explore the use of [G1K,K8R]cGm, a designed cyclic analogue of the antimicrobial peptide gomesin, as an alternative approach to treat biofilm infections. Methods: We studied the activity of [G1K,K8R]cGm against biofilms of Staphylococcus aureus, a pathogen associated with several biofilm-related infections. A combination of atomic force and real-time confocal laser scanning microscopies was used to study the mechanism of action of the peptide. Results: The peptide demonstrated potent activity against 24 h-preformed biofilms through a concentration-dependent ability to kill biofilm-embedded cells. Mechanistic studies showed that [G1K,K8R]cGm causes morphological changes on bacterial cells and permeabilizes their membranes across the biofilm with a half-time of 65 min. We also tested an analogue of [G1K,K8R]cGm without disulphide bonds, and a linear unfolded analogue, and found both to be inactive. Conclusions: The results suggest that the 3D structure of [G1K,K8R]cGm and its stabilization by disulphide bonds are essential for its antibacterial and antibiofilm activities. Moreover, our findings support the potential application of this stable cyclic antimicrobial peptide to fight bacterial biofilms.This project received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 828774. This work was supported by project grants funded by Fundação para a Ciência e a Tecnologia (FCT-MCTES, Portugal; UIDB/04565/2020 and PPBI-POCI-01-0145-FEDER-022122). S.A.D. acknowledges FCT for the fellowship PD/BD/114425/2016. S.T.H. is an Australian Research Council (ARC) Future Fellow (FT150100398) and is supported by the ARC Centre of Excellence for Innovations in Peptide & Protein Science (CE200100012).Oxford University PressRepositório da Universidade de LisboaDias, SusanaPinto, SandraSilva-Herdade, Ana S.Cheneval, OlivierCraik, David JCoutinho, AnaCastanho, Miguel A. R. B.Henriques, Sónia T.Veiga, Ana Salomé2022-09-30T14:32:39Z20222022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/54640engJ Antimicrob Chemother. 2022 Sep 29;dkac3090305-745310.1093/jac/dkac3091460-2091info: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:RCAAP2023-11-08T17:01:09Zoai:repositorio.ul.pt:10451/54640Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:05:26.031832Repositório 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 |
A designed cyclic analogue of gomesin has potent activity against Staphylococcus aureus biofilms |
| title |
A designed cyclic analogue of gomesin has potent activity against Staphylococcus aureus biofilms |
| spellingShingle |
A designed cyclic analogue of gomesin has potent activity against Staphylococcus aureus biofilms Dias, Susana |
| title_short |
A designed cyclic analogue of gomesin has potent activity against Staphylococcus aureus biofilms |
| title_full |
A designed cyclic analogue of gomesin has potent activity against Staphylococcus aureus biofilms |
| title_fullStr |
A designed cyclic analogue of gomesin has potent activity against Staphylococcus aureus biofilms |
| title_full_unstemmed |
A designed cyclic analogue of gomesin has potent activity against Staphylococcus aureus biofilms |
| title_sort |
A designed cyclic analogue of gomesin has potent activity against Staphylococcus aureus biofilms |
| author |
Dias, Susana |
| author_facet |
Dias, Susana Pinto, Sandra Silva-Herdade, Ana S. Cheneval, Olivier Craik, David J Coutinho, Ana Castanho, Miguel A. R. B. Henriques, Sónia T. Veiga, Ana Salomé |
| author_role |
author |
| author2 |
Pinto, Sandra Silva-Herdade, Ana S. Cheneval, Olivier Craik, David J Coutinho, Ana Castanho, Miguel A. R. B. Henriques, Sónia T. Veiga, Ana Salomé |
| author2_role |
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 |
Dias, Susana Pinto, Sandra Silva-Herdade, Ana S. Cheneval, Olivier Craik, David J Coutinho, Ana Castanho, Miguel A. R. B. Henriques, Sónia T. Veiga, Ana Salomé |
| description |
© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https:// 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 |
2022 |
| dc.date.none.fl_str_mv |
2022-09-30T14:32:39Z 2022 2022-01-01T00:00:00Z |
| 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/10451/54640 |
| url |
http://hdl.handle.net/10451/54640 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
J Antimicrob Chemother. 2022 Sep 29;dkac309 0305-7453 10.1093/jac/dkac309 1460-2091 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Oxford University Press |
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Oxford University Press |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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