Antimicrobial peptides can generate tolerance by lag and interfere with antimicrobial therapy
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- dc.contributor.author Sandín, Daniel
- dc.contributor.author Valle, Javier
- dc.contributor.author Morata, Jordi
- dc.contributor.author Andreu Martínez, David
- dc.contributor.author Torrent Burgas, Marc
- dc.date.accessioned 2022-12-20T07:01:15Z
- dc.date.available 2022-12-20T07:01:15Z
- dc.date.issued 2022
- dc.description.abstract 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.
- dc.description.sponsorship 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.
- dc.format.mimetype application/pdf
- dc.identifier.citation Sandín D, Valle J, Morata J, Andreu D, Torrent M. Antimicrobial peptides can generate tolerance by lag and interfere with antimicrobial therapy. Pharmaceutics. 2022 Oct 11;14(10):2169. DOI: 10.3390/pharmaceutics14102169
- dc.identifier.doi http://dx.doi.org/10.3390/pharmaceutics14102169
- dc.identifier.issn 1999-4923
- dc.identifier.uri http://hdl.handle.net/10230/55172
- dc.language.iso eng
- dc.publisher MDPI
- dc.relation.ispartof Pharmaceutics. 2022 Oct 11;14(10):2169
- dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PDC2021-121544-I00
- dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2020-114627RB-I00
- dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/AGL2017-84097-C2-2-R
- dc.rights © 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/).
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri https://creativecommons.org/licenses/by/4.0/
- dc.subject.keyword Antimicrobial peptide LL-37
- dc.subject.keyword Antimicrobial peptides
- dc.subject.keyword Dermaseptin
- dc.subject.keyword Pleurocidin
- dc.subject.keyword Polymyxin B
- dc.subject.keyword Tolerance
- dc.title Antimicrobial peptides can generate tolerance by lag and interfere with antimicrobial therapy
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion