Resistance to the Bacteriocin Lcn972 Deciphered by Genome Sequencing

In view of the current threat of antibiotic resistance, new antimicrobials with low risk of resistance development are demanded. Lcn972 is a lactococcal bacteriocin that inhibits septum formation by binding to the cell wall precursor lipid II in Lactococcus. It has a species-specific spectrum of act...

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Autores: Escobedo, Susana, Campelo, Ana B., Umu, Özgün C. O., López-González, María Jesús, Rodríguez González, Ana, Diep, Dzung B., Martínez Fernández, Beatriz
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:dnet:digitalcsic_::99219225058e09861d55f8056160160d
Acceso en línea:http://hdl.handle.net/10261/295604
Access Level:acceso abierto
Palabra clave:Lactococcus
Bacteriocin
Resistance
Adaptive evolution
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spelling Resistance to the Bacteriocin Lcn972 Deciphered by Genome SequencingEscobedo, SusanaCampelo, Ana B.Umu, Özgün C. O.López-González, María JesúsRodríguez González, AnaDiep, Dzung B.Martínez Fernández, BeatrizLactococcusBacteriocinResistanceAdaptive evolutionIn view of the current threat of antibiotic resistance, new antimicrobials with low risk of resistance development are demanded. Lcn972 is a lactococcal bacteriocin that inhibits septum formation by binding to the cell wall precursor lipid II in Lactococcus. It has a species-specific spectrum of activity, making Lcn972 an attractive template to develop or improve existing antibiotics. The aim of this work was to identify mutations present in the Lcn972-resistant clone Lactococcus cremoris D1-20, previously evolved from the sensitive strain L. cremoris MG1614. Whole-genome sequencing and comparison over the reference genome L. cremoris MG1363 identified several unexpected mutations in the parental strain MG1614, likely selected during in-house propagation. In the Lcn972R clone, two previously identified mutations were mapped and confirmed. Additionally, another transposition event deregulating cellobiose uptake was identified along with three point mutations of unknown consequences for Lcn972 resistance. Two new independent evolution experiments exposing L. cremoris MG1614 to Lcn972 revealed transposition of IS981 into the LLMG_RS12285 locus as the predominant mutation selected by Lcn972. This event occurs early during evolution and was found in 100% of the evolved clones, while other mutations were not selected. Therefore, activation of LLMG_RS12285 coding for a putative anti-ECF (extra-cytoplasmic function) sigma factor is regarded as the main Lcn972 resistance factor in L. cremoris MG1614.This work was funded by grant PID2020-119697RB-I00 funded by MCIN/AEI/10.13039/501100011033 and grant AYUD/2021/52120 (Program of Science, Technology and Innovation 2018–2022, Principado de Asturias, FICYT, FEDER-UE). Ö.C.O. Umu, D.B. Diep and B. Martínez were recipients of a mobility grant Spain-Norway, supported by EEA Coordinated Mobility of Researchers NILS Science and Sustainability Project 017-CM-01-2013.Peer reviewedMolecular Diversity Preservation InternationalAgencia Estatal de Investigación (España)Ministerio de Ciencia, Innovación y Universidades (España)Fundación para la Investigación y la Innovación Biosanitaria del Principado de AsturiasEuropean CommissionPrincipado de AsturiasUmu, Özgün C. O. [0000-0003-4060-7766]Martínez Fernández, Beatriz [0000-0001-7692-1963]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202320232023info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/295604reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-119697RB-I00The underlying dataset has been published as supplementary material of the article in the publisher platform at https://doi.org/10.3390/microorganisms11020501https://doi.org/10.3390/microorganisms11020501Síinfo:eu-repo/semantics/openAccessoai:dnet:digitalcsic_::99219225058e09861d55f8056160160d2026-05-22T06:33:51Z
dc.title.none.fl_str_mv Resistance to the Bacteriocin Lcn972 Deciphered by Genome Sequencing
title Resistance to the Bacteriocin Lcn972 Deciphered by Genome Sequencing
spellingShingle Resistance to the Bacteriocin Lcn972 Deciphered by Genome Sequencing
Escobedo, Susana
Lactococcus
Bacteriocin
Resistance
Adaptive evolution
title_short Resistance to the Bacteriocin Lcn972 Deciphered by Genome Sequencing
title_full Resistance to the Bacteriocin Lcn972 Deciphered by Genome Sequencing
title_fullStr Resistance to the Bacteriocin Lcn972 Deciphered by Genome Sequencing
title_full_unstemmed Resistance to the Bacteriocin Lcn972 Deciphered by Genome Sequencing
title_sort Resistance to the Bacteriocin Lcn972 Deciphered by Genome Sequencing
dc.creator.none.fl_str_mv Escobedo, Susana
Campelo, Ana B.
Umu, Özgün C. O.
López-González, María Jesús
Rodríguez González, Ana
Diep, Dzung B.
Martínez Fernández, Beatriz
author Escobedo, Susana
author_facet Escobedo, Susana
Campelo, Ana B.
Umu, Özgün C. O.
López-González, María Jesús
Rodríguez González, Ana
Diep, Dzung B.
Martínez Fernández, Beatriz
author_role author
author2 Campelo, Ana B.
Umu, Özgün C. O.
López-González, María Jesús
Rodríguez González, Ana
Diep, Dzung B.
Martínez Fernández, Beatriz
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Agencia Estatal de Investigación (España)
Ministerio de Ciencia, Innovación y Universidades (España)
Fundación para la Investigación y la Innovación Biosanitaria del Principado de Asturias
European Commission
Principado de Asturias
Umu, Özgün C. O. [0000-0003-4060-7766]
Martínez Fernández, Beatriz [0000-0001-7692-1963]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Lactococcus
Bacteriocin
Resistance
Adaptive evolution
topic Lactococcus
Bacteriocin
Resistance
Adaptive evolution
description In view of the current threat of antibiotic resistance, new antimicrobials with low risk of resistance development are demanded. Lcn972 is a lactococcal bacteriocin that inhibits septum formation by binding to the cell wall precursor lipid II in Lactococcus. It has a species-specific spectrum of activity, making Lcn972 an attractive template to develop or improve existing antibiotics. The aim of this work was to identify mutations present in the Lcn972-resistant clone Lactococcus cremoris D1-20, previously evolved from the sensitive strain L. cremoris MG1614. Whole-genome sequencing and comparison over the reference genome L. cremoris MG1363 identified several unexpected mutations in the parental strain MG1614, likely selected during in-house propagation. In the Lcn972R clone, two previously identified mutations were mapped and confirmed. Additionally, another transposition event deregulating cellobiose uptake was identified along with three point mutations of unknown consequences for Lcn972 resistance. Two new independent evolution experiments exposing L. cremoris MG1614 to Lcn972 revealed transposition of IS981 into the LLMG_RS12285 locus as the predominant mutation selected by Lcn972. This event occurs early during evolution and was found in 100% of the evolved clones, while other mutations were not selected. Therefore, activation of LLMG_RS12285 coding for a putative anti-ECF (extra-cytoplasmic function) sigma factor is regarded as the main Lcn972 resistance factor in L. cremoris MG1614.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023
2023
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/10261/295604
url http://hdl.handle.net/10261/295604
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-119697RB-I00
The underlying dataset has been published as supplementary material of the article in the publisher platform at https://doi.org/10.3390/microorganisms11020501
https://doi.org/10.3390/microorganisms11020501
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Molecular Diversity Preservation International
publisher.none.fl_str_mv Molecular Diversity Preservation International
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
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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