Antimicrobial peptides can generate tolerance by lag and interfere with antimicrobial therapy

Antimicrobial peptides (AMPs) are widely distributed molecules secreted mostly by cells of the innate immune system to prevent bacterial proliferation at the site of infection. As with classic antibiotics, continued treatment with AMPs can create resistance in bacteria. However, whether AMPs can gen...

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Autores: Sandín, Daniel, Valle, Javier, Morata, Jordi, Andreu Martínez, David, Torrent Burgas, Marc
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/55172
Acceso en línea:http://hdl.handle.net/10230/55172
http://dx.doi.org/10.3390/pharmaceutics14102169
Access Level:acceso abierto
Palabra clave:Antimicrobial peptide LL-37
Antimicrobial peptides
Dermaseptin
Pleurocidin
Polymyxin B
Tolerance
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spelling Antimicrobial peptides can generate tolerance by lag and interfere with antimicrobial therapySandín, DanielValle, JavierMorata, JordiAndreu Martínez, DavidTorrent Burgas, MarcAntimicrobial peptide LL-37Antimicrobial peptidesDermaseptinPleurocidinPolymyxin BToleranceAntimicrobial peptides (AMPs) are widely distributed molecules secreted mostly by cells of the innate immune system to prevent bacterial proliferation at the site of infection. As with classic antibiotics, continued treatment with AMPs can create resistance in bacteria. However, whether AMPs can generate tolerance as an intermediate stage towards resistance is not known. Here, we show that the treatment of Escherichia coli with different AMPs induces tolerance by lag, particularly for those peptides that have internal targets. This tolerance can be detected as different morphological and physiological changes, which depend on the type of peptide molecule the bacterium has been exposed to. In addition, we show that AMP tolerance can also affect antibiotic treatment. The genomic sequencing of AMP-tolerant strains shows that different mutations alter membrane composition, DNA replication, and translation. Some of these mutations have also been observed in antibiotic-resistant strains, suggesting that AMP tolerance could be a relevant step in the development of antibiotic resistance. Monitoring AMP tolerance is relevant vis-á-vis the eventual therapeutic use of AMPs and because cross-tolerance might favor the emergence of resistance against conventional antibiotic treatments.Financial support from the Spanish Ministry of Economy and Innovation (PDC2021-121544-I00 funded by MCIN/AEI /10.13039/501100011033 and European Union Next GenerationEU/ PRTR to M.T.; project PID2020-114627RB-I00 funded by MCIN/ AEI /10.13039/501100011033 to M.T. and AGL2017-84097-C2-2-R to D.A.), and from La Caixa Banking Foundation (HR17-00409, to D.A.). Work at UPF was funded by the MCI María de Maeztu network of Units of Excellence. D.S. is recipient of pre-doctoral a FPI scholarship (PRE2018-083243) from the Spanish Ministerio de Ciencia e Innovación.MDPI202220222022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/55172http://dx.doi.org/10.3390/pharmaceutics14102169reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésPharmaceutics. 2022 Oct 11;14(10):2169info:eu-repo/grantAgreement/ES/3PE/PDC2021-121544-I00info:eu-repo/grantAgreement/ES/2PE/PID2020-114627RB-I00info:eu-repo/grantAgreement/ES/2PE/AGL2017-84097-C2-2-R© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/551722026-06-12T07:21:37Z
dc.title.none.fl_str_mv Antimicrobial peptides can generate tolerance by lag and interfere with antimicrobial therapy
title Antimicrobial peptides can generate tolerance by lag and interfere with antimicrobial therapy
spellingShingle Antimicrobial peptides can generate tolerance by lag and interfere with antimicrobial therapy
Sandín, Daniel
Antimicrobial peptide LL-37
Antimicrobial peptides
Dermaseptin
Pleurocidin
Polymyxin B
Tolerance
title_short Antimicrobial peptides can generate tolerance by lag and interfere with antimicrobial therapy
title_full Antimicrobial peptides can generate tolerance by lag and interfere with antimicrobial therapy
title_fullStr Antimicrobial peptides can generate tolerance by lag and interfere with antimicrobial therapy
title_full_unstemmed Antimicrobial peptides can generate tolerance by lag and interfere with antimicrobial therapy
title_sort Antimicrobial peptides can generate tolerance by lag and interfere with antimicrobial therapy
dc.creator.none.fl_str_mv Sandín, Daniel
Valle, Javier
Morata, Jordi
Andreu Martínez, David
Torrent Burgas, Marc
author Sandín, Daniel
author_facet Sandín, Daniel
Valle, Javier
Morata, Jordi
Andreu Martínez, David
Torrent Burgas, Marc
author_role author
author2 Valle, Javier
Morata, Jordi
Andreu Martínez, David
Torrent Burgas, Marc
author2_role author
author
author
author
dc.subject.none.fl_str_mv Antimicrobial peptide LL-37
Antimicrobial peptides
Dermaseptin
Pleurocidin
Polymyxin B
Tolerance
topic Antimicrobial peptide LL-37
Antimicrobial peptides
Dermaseptin
Pleurocidin
Polymyxin B
Tolerance
description Antimicrobial peptides (AMPs) are widely distributed molecules secreted mostly by cells of the innate immune system to prevent bacterial proliferation at the site of infection. As with classic antibiotics, continued treatment with AMPs can create resistance in bacteria. However, whether AMPs can generate tolerance as an intermediate stage towards resistance is not known. Here, we show that the treatment of Escherichia coli with different AMPs induces tolerance by lag, particularly for those peptides that have internal targets. This tolerance can be detected as different morphological and physiological changes, which depend on the type of peptide molecule the bacterium has been exposed to. In addition, we show that AMP tolerance can also affect antibiotic treatment. The genomic sequencing of AMP-tolerant strains shows that different mutations alter membrane composition, DNA replication, and translation. Some of these mutations have also been observed in antibiotic-resistant strains, suggesting that AMP tolerance could be a relevant step in the development of antibiotic resistance. Monitoring AMP tolerance is relevant vis-á-vis the eventual therapeutic use of AMPs and because cross-tolerance might favor the emergence of resistance against conventional antibiotic treatments.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/55172
http://dx.doi.org/10.3390/pharmaceutics14102169
url http://hdl.handle.net/10230/55172
http://dx.doi.org/10.3390/pharmaceutics14102169
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Pharmaceutics. 2022 Oct 11;14(10):2169
info:eu-repo/grantAgreement/ES/3PE/PDC2021-121544-I00
info:eu-repo/grantAgreement/ES/2PE/PID2020-114627RB-I00
info:eu-repo/grantAgreement/ES/2PE/AGL2017-84097-C2-2-R
dc.rights.none.fl_str_mv https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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