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...
- 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
- 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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|
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 |
dc.format.mimetype.none.fl_str_mv |
application/pdf |
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 |
bitstream.url.fl_str_mv |
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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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 |