Antimicrobial Peptide Exposure Selects for Resistant and Fit Stenotrophomonas maltophilia Mutants That Show Cross-Resistance to Antibiotics

© 2020 Blanco et al.

Detalles Bibliográficos
Autores: Blanco, Paula, Hjort, Karin, Martínez, José L.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/228725
Acceso en línea:http://hdl.handle.net/10261/228725
Access Level:acceso abierto
Palabra clave:Stenotrophomonas
Antibiotic resistance
Antimicrobial peptides
Crossresistance
Drug resistance evolution
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spelling Antimicrobial Peptide Exposure Selects for Resistant and Fit Stenotrophomonas maltophilia Mutants That Show Cross-Resistance to AntibioticsBlanco, PaulaHjort, KarinMartínez, José L.StenotrophomonasAntibiotic resistanceAntimicrobial peptidesCrossresistanceDrug resistance evolution© 2020 Blanco et al.Antimicrobial peptides (AMPs) are essential components of the innate immune system and have been proposed as promising therapeutic agents against drug-resistant microbes. AMPs possess a rapid bactericidal mode of action and can interact with different targets, but bacteria can also avoid their effect through a variety of resistance mechanisms. Apart from hampering treatment by the AMP itself, or that by other antibiotics in the case of cross-resistance, AMP resistance might also confer cross-resistance to innate human peptides and impair the anti-infective capability of the human host. A better understanding of how resistance to AMPs is acquired and the genetic mechanisms involved is needed before using these compounds as therapeutic agents. Using experimental evolution and whole-genome sequencing, we determined the genetic causes and the effect of acquired de novo resistance to three different AMPs in the opportunistic pathogen Stenotrophomonas maltophilia, a bacterium that is intrinsically resistant to a wide range of antibiotics. Our results show that AMP exposure selects for high-level resistance, generally without any reduction in bacterial fitness, conferred by mutations in different genes encoding enzymes, transporters, transcriptional regulators, and other functions. Cross-resistance to AMPs and to other antibiotic classes not used for selection, as well as collateral sensitivity, was observed for many of the evolved populations. The relative ease by which high-level AMP resistance is acquired, combined with the occurrence of cross-resistance to conventional antibiotics and the maintained bacterial fitness of the analyzed mutants, highlights the need for careful studies of S. maltophilia resistance evolution to clinically valuable AMPs.This research was supported by a grant from the Swedish Research Council (grant 2017-01527) to D.I.A. and a grant from the Spanish Ministry of Economy and Competitiveness (BIO2017-83128-R) to J.L.M. P.B. is the recipient of an FPI fellowship from the Spanish Ministry of Economy, Industry and Competitivity, and her work was supported by an EMBO Short-Term Fellowship.American Society for MicrobiologySwedish Research CouncilMinisterio de Ciencia, Innovación y Universidades (España)Agencia Estatal de Investigación (España)EMBOMinisterio de Economía, Industria y Competitividad (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2021202120202021info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/228725reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/BIO2017-83128-RBIO2017-83128-R/AEI/10.13039/501100011033http://dx.doi.org/10.1128/mSphere.00717-20Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2287252026-05-22T06:33:51Z
dc.title.none.fl_str_mv Antimicrobial Peptide Exposure Selects for Resistant and Fit Stenotrophomonas maltophilia Mutants That Show Cross-Resistance to Antibiotics
title Antimicrobial Peptide Exposure Selects for Resistant and Fit Stenotrophomonas maltophilia Mutants That Show Cross-Resistance to Antibiotics
spellingShingle Antimicrobial Peptide Exposure Selects for Resistant and Fit Stenotrophomonas maltophilia Mutants That Show Cross-Resistance to Antibiotics
Blanco, Paula
Stenotrophomonas
Antibiotic resistance
Antimicrobial peptides
Crossresistance
Drug resistance evolution
title_short Antimicrobial Peptide Exposure Selects for Resistant and Fit Stenotrophomonas maltophilia Mutants That Show Cross-Resistance to Antibiotics
title_full Antimicrobial Peptide Exposure Selects for Resistant and Fit Stenotrophomonas maltophilia Mutants That Show Cross-Resistance to Antibiotics
title_fullStr Antimicrobial Peptide Exposure Selects for Resistant and Fit Stenotrophomonas maltophilia Mutants That Show Cross-Resistance to Antibiotics
title_full_unstemmed Antimicrobial Peptide Exposure Selects for Resistant and Fit Stenotrophomonas maltophilia Mutants That Show Cross-Resistance to Antibiotics
title_sort Antimicrobial Peptide Exposure Selects for Resistant and Fit Stenotrophomonas maltophilia Mutants That Show Cross-Resistance to Antibiotics
dc.creator.none.fl_str_mv Blanco, Paula
Hjort, Karin
Martínez, José L.
author Blanco, Paula
author_facet Blanco, Paula
Hjort, Karin
Martínez, José L.
author_role author
author2 Hjort, Karin
Martínez, José L.
author2_role author
author
dc.contributor.none.fl_str_mv Swedish Research Council
Ministerio de Ciencia, Innovación y Universidades (España)
Agencia Estatal de Investigación (España)
EMBO
Ministerio de Economía, Industria y Competitividad (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Stenotrophomonas
Antibiotic resistance
Antimicrobial peptides
Crossresistance
Drug resistance evolution
topic Stenotrophomonas
Antibiotic resistance
Antimicrobial peptides
Crossresistance
Drug resistance evolution
description © 2020 Blanco et al.
publishDate 2020
dc.date.none.fl_str_mv 2020
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/228725
url http://hdl.handle.net/10261/228725
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/BIO2017-83128-R
BIO2017-83128-R/AEI/10.13039/501100011033
http://dx.doi.org/10.1128/mSphere.00717-20
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
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