Antimicrobial sensing coupled with cell membrane remodeling mediates antibiotic resistance and virulence in enterococcus faecalis

Bacteria have developed several evolutionary strategies to protect their cell membranes (CMs) from the attack of antibiotics and antimicrobial peptides (AMPs) produced by the innate immune system, including remodeling of phospholipid content and localization. Multidrug-resistant Enterococcus faecali...

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Autores:
Khan, Ayesha
Davlieva, Milya
Panesso, Diana
Rincon Núñez, Sandra
Millera, William R.
Diaz, Lorena
Reyes, Jinnethe
Cruz, Melissa R.
Pemberton, Orville
Nguyen, April H.
Siegel, Sara D.
Planet, Paul J.
Narechania, Apurva
Latorre, Mauricio
Rios, Rafael
Singh, Kavindra V.
Ton-That, Hung
Garsin, Danielle A.
Tran, Truc T.
Shamoo, Yousif
Arias, Cesar A
Tipo de recurso:
Fecha de publicación:
2020
Institución:
Universidad El Bosque
Repositorio:
Repositorio U. El Bosque
Idioma:
eng
OAI Identifier:
oai:repositorio.unbosque.edu.co:20.500.12495/2161
Acceso en línea:
http://hdl.handle.net/20.500.12495/2161
https://doi.org/10.1073/pnas.1916037116
Palabra clave:
Enterococos resistentes a la vancomicina
Farmacorresistencia microbiana
Estructuras de la membrana celular
Antibiotic resistance
Enterococcus faecalis
Daptomycin
Cell membrane adaptation
Antimicrobial
Peptides
Rights
License
Attribution-NonCommercial-NoDerivatives 4.0 International
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oai_identifier_str oai:repositorio.unbosque.edu.co:20.500.12495/2161
network_acronym_str UNBOSQUE2
network_name_str Repositorio U. El Bosque
repository_id_str
dc.title.spa.fl_str_mv Antimicrobial sensing coupled with cell membrane remodeling mediates antibiotic resistance and virulence in enterococcus faecalis
dc.title.translated.none.fl_str_mv Antimicrobial sensing coupled with cell membrane remodeling mediates antibiotic resistance and virulence in enterococcus faecalis
title Antimicrobial sensing coupled with cell membrane remodeling mediates antibiotic resistance and virulence in enterococcus faecalis
spellingShingle Antimicrobial sensing coupled with cell membrane remodeling mediates antibiotic resistance and virulence in enterococcus faecalis
Enterococos resistentes a la vancomicina
Farmacorresistencia microbiana
Estructuras de la membrana celular
Antibiotic resistance
Enterococcus faecalis
Daptomycin
Cell membrane adaptation
Antimicrobial
Peptides
title_short Antimicrobial sensing coupled with cell membrane remodeling mediates antibiotic resistance and virulence in enterococcus faecalis
title_full Antimicrobial sensing coupled with cell membrane remodeling mediates antibiotic resistance and virulence in enterococcus faecalis
title_fullStr Antimicrobial sensing coupled with cell membrane remodeling mediates antibiotic resistance and virulence in enterococcus faecalis
title_full_unstemmed Antimicrobial sensing coupled with cell membrane remodeling mediates antibiotic resistance and virulence in enterococcus faecalis
title_sort Antimicrobial sensing coupled with cell membrane remodeling mediates antibiotic resistance and virulence in enterococcus faecalis
dc.creator.fl_str_mv Khan, Ayesha
Davlieva, Milya
Panesso, Diana
Rincon Núñez, Sandra
Millera, William R.
Diaz, Lorena
Reyes, Jinnethe
Cruz, Melissa R.
Pemberton, Orville
Nguyen, April H.
Siegel, Sara D.
Planet, Paul J.
Narechania, Apurva
Latorre, Mauricio
Rios, Rafael
Singh, Kavindra V.
Ton-That, Hung
Garsin, Danielle A.
Tran, Truc T.
Shamoo, Yousif
Arias, Cesar A
dc.contributor.author.none.fl_str_mv Khan, Ayesha
Davlieva, Milya
Panesso, Diana
Rincon Núñez, Sandra
Millera, William R.
Diaz, Lorena
Reyes, Jinnethe
Cruz, Melissa R.
Pemberton, Orville
Nguyen, April H.
Siegel, Sara D.
Planet, Paul J.
Narechania, Apurva
Latorre, Mauricio
Rios, Rafael
Singh, Kavindra V.
Ton-That, Hung
Garsin, Danielle A.
Tran, Truc T.
Shamoo, Yousif
Arias, Cesar A
dc.contributor.orcid.none.fl_str_mv Panesso, Diana [0000-0002-4049-9702]
Rincon Núñez, Sandra [0000-0002-8482-4554]
dc.subject.decs.spa.fl_str_mv Enterococos resistentes a la vancomicina
Farmacorresistencia microbiana
Estructuras de la membrana celular
topic Enterococos resistentes a la vancomicina
Farmacorresistencia microbiana
Estructuras de la membrana celular
Antibiotic resistance
Enterococcus faecalis
Daptomycin
Cell membrane adaptation
Antimicrobial
Peptides
dc.subject.keywords.spa.fl_str_mv Antibiotic resistance
Enterococcus faecalis
Daptomycin
Cell membrane adaptation
Antimicrobial
Peptides
description Bacteria have developed several evolutionary strategies to protect their cell membranes (CMs) from the attack of antibiotics and antimicrobial peptides (AMPs) produced by the innate immune system, including remodeling of phospholipid content and localization. Multidrug-resistant Enterococcus faecalis, an opportunistic human pathogen, evolves resistance to the lipopeptide daptomycin and AMPs by diverting the antibiotic away from critical septal targets using CM anionic phospholipid redistribution. The LiaFSR stress response system regulates this CM remodeling via the LiaR response regulator by a previously unknown mechanism. Here, we characterize a LiaR-regulated protein, LiaX, that senses daptomycin or AMPs and triggers protective CM remodeling. LiaX is surface exposed, and in daptomycin-resistant clinical strains, both LiaX and the N-terminal domain alone are released into the extracellular milieu. The N-terminal domain of LiaX binds daptomycin and AMPs (such as human LL-37) and functions as an extracellular sentinel that activates the cell envelope stress response. The C-terminal domain of LiaX plays a role in inhibiting the LiaFSR system, and when this domain is absent, it leads to activation of anionic phospholipid redistribution. Strains that exhibit LiaX-mediated CM remodeling and AMP resistance show enhanced virulence in the Caenorhabditis elegans model, an effect that is abolished in animals lacking an innate immune pathway crucial for producing AMPs. In conclusion, we report a mechanism of antibiotic and AMP resistance that couples bacterial stress sensing to major changes in CM architecture, ultimately also affecting host–pathogen interactions.
publishDate 2020
dc.date.accessioned.none.fl_str_mv 2020-03-26T22:48:02Z
dc.date.available.none.fl_str_mv 2020-03-26T22:48:02Z
dc.date.issued.none.fl_str_mv 2020
dc.type.spa.fl_str_mv article
dc.type.coarversion.fl_str_mv http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.coar.fl_str_mv http://purl.org/coar/resource_type/c_6501
dc.type.local.spa.fl_str_mv artículo
dc.identifier.issn.none.fl_str_mv 1091-6490
dc.identifier.uri.none.fl_str_mv http://hdl.handle.net/20.500.12495/2161
dc.identifier.doi.none.fl_str_mv https://doi.org/10.1073/pnas.1916037116
dc.identifier.instname.spa.fl_str_mv instname:Universidad El Bosque
dc.identifier.reponame.spa.fl_str_mv reponame:Repositorio Institucional Universidad El Bosque
dc.identifier.repourl.none.fl_str_mv repourl:https://repositorio.unbosque.edu.co
identifier_str_mv 1091-6490
instname:Universidad El Bosque
reponame:Repositorio Institucional Universidad El Bosque
repourl:https://repositorio.unbosque.edu.co
url http://hdl.handle.net/20.500.12495/2161
https://doi.org/10.1073/pnas.1916037116
dc.language.iso.none.fl_str_mv eng
language eng
dc.relation.ispartofseries.spa.fl_str_mv Proceedings of the National Academy of Sciences, 1091-6490, Vol 116, Núm 52, pag 26925–26932
dc.relation.uri.none.fl_str_mv https://www.pnas.org/content/116/52/26925
dc.rights.*.fl_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.coar.fl_str_mv http://purl.org/coar/access_right/c_abf2
dc.rights.uri.*.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.local.spa.fl_str_mv Acceso abierto
dc.rights.accessrights.none.fl_str_mv http://purl.org/coar/access_right/c_abf184
dc.rights.creativecommons.none.fl_str_mv 2019
rights_invalid_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
Acceso abierto
http://purl.org/coar/access_right/c_abf184
2019
http://purl.org/coar/access_right/c_abf2
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dc.publisher.spa.fl_str_mv National Academy of Sciences
dc.publisher.journal.spa.fl_str_mv Proceedings of the National Academy of Sciences
institution Universidad El Bosque
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spelling Khan, AyeshaDavlieva, MilyaPanesso, DianaRincon Núñez, SandraMillera, William R.Diaz, LorenaReyes, JinnetheCruz, Melissa R.Pemberton, OrvilleNguyen, April H.Siegel, Sara D.Planet, Paul J.Narechania, ApurvaLatorre, MauricioRios, RafaelSingh, Kavindra V.Ton-That, HungGarsin, Danielle A.Tran, Truc T.Shamoo, YousifArias, Cesar APanesso, Diana [0000-0002-4049-9702]Rincon Núñez, Sandra [0000-0002-8482-4554]2020-03-26T22:48:02Z2020-03-26T22:48:02Z20201091-6490http://hdl.handle.net/20.500.12495/2161https://doi.org/10.1073/pnas.1916037116instname:Universidad El Bosquereponame:Repositorio Institucional Universidad El Bosquerepourl:https://repositorio.unbosque.edu.coapplication/pdfengNational Academy of SciencesProceedings of the National Academy of SciencesProceedings of the National Academy of Sciences, 1091-6490, Vol 116, Núm 52, pag 26925–26932https://www.pnas.org/content/116/52/26925Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/Acceso abiertohttp://purl.org/coar/access_right/c_abf1842019http://purl.org/coar/access_right/c_abf2Antimicrobial sensing coupled with cell membrane remodeling mediates antibiotic resistance and virulence in enterococcus faecalisAntimicrobial sensing coupled with cell membrane remodeling mediates antibiotic resistance and virulence in enterococcus faecalisarticleartículohttp://purl.org/coar/version/c_970fb48d4fbd8a85http://purl.org/coar/resource_type/c_6501Enterococos resistentes a la vancomicinaFarmacorresistencia microbianaEstructuras de la membrana celularAntibiotic resistanceEnterococcus faecalisDaptomycinCell membrane adaptationAntimicrobialPeptidesBacteria have developed several evolutionary strategies to protect their cell membranes (CMs) from the attack of antibiotics and antimicrobial peptides (AMPs) produced by the innate immune system, including remodeling of phospholipid content and localization. Multidrug-resistant Enterococcus faecalis, an opportunistic human pathogen, evolves resistance to the lipopeptide daptomycin and AMPs by diverting the antibiotic away from critical septal targets using CM anionic phospholipid redistribution. The LiaFSR stress response system regulates this CM remodeling via the LiaR response regulator by a previously unknown mechanism. Here, we characterize a LiaR-regulated protein, LiaX, that senses daptomycin or AMPs and triggers protective CM remodeling. LiaX is surface exposed, and in daptomycin-resistant clinical strains, both LiaX and the N-terminal domain alone are released into the extracellular milieu. The N-terminal domain of LiaX binds daptomycin and AMPs (such as human LL-37) and functions as an extracellular sentinel that activates the cell envelope stress response. The C-terminal domain of LiaX plays a role in inhibiting the LiaFSR system, and when this domain is absent, it leads to activation of anionic phospholipid redistribution. Strains that exhibit LiaX-mediated CM remodeling and AMP resistance show enhanced virulence in the Caenorhabditis elegans model, an effect that is abolished in animals lacking an innate immune pathway crucial for producing AMPs. In conclusion, we report a mechanism of antibiotic and AMP resistance that couples bacterial stress sensing to major changes in CM architecture, ultimately also affecting host–pathogen interactions.ORIGINALKhan, Ayesha.pdfKhan, Ayesha.pdfapplication/pdf1462371https://repositorio.unbosque.edu.co/bitstreams/7ce361c3-8a8f-44da-8f7b-456db24a7642/downloadcaffd1fd99c01bdae66f9aa3c6f16d9fMD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8805https://repositorio.unbosque.edu.co/bitstreams/13d3e153-357b-4db5-bb7a-eef4bd00b241/download4460e5956bc1d1639be9ae6146a50347MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-81748https://repositorio.unbosque.edu.co/bitstreams/150f21de-2d43-40b4-be38-ee221dbd64a3/download8a4605be74aa9ea9d79846c1fba20a33MD53THUMBNAILKhan, Ayesha.pdf.jpgKhan, Ayesha.pdf.jpgIM Thumbnailimage/jpeg15227https://repositorio.unbosque.edu.co/bitstreams/726e6514-0a16-44b0-b012-77cfcb724f72/download285e800473f490d92ed16a6fb6626974MD54TEXTKhan, Ayesha.pdf.txtKhan, Ayesha.pdf.txtExtracted texttext/plain59128https://repositorio.unbosque.edu.co/bitstreams/4b36a64a-041f-454c-8a50-9ed7b156d462/download30be94a8956dd8cff09eb337cbc6d5e9MD5520.500.12495/2161oai:repositorio.unbosque.edu.co:20.500.12495/21612024-02-06 23:20:34.862http://creativecommons.org/licenses/by-nc-nd/4.0/Attribution-NonCommercial-NoDerivatives 4.0 Internationalopen.accesshttps://repositorio.unbosque.edu.coRepositorio Institucional Universidad El Bosquebibliotecas@biteca.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