Membrane anchoring stabilizes and favors secretion of New Delhi metallo-β-lactamase

Autores
Gonzalez, Lisandro Javier; Bahr, Guillermo; Nakashige, Toshiki G.; Nolan, Elizabeth M.; Bonomo, Robert A.; Vila, Alejandro Jose
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Carbapenems, 'last-resort' β-lactam antibiotics, are inactivated by zinc-dependent metallo-β-lactamases (MBLs). The host innate immune response withholds nutrient metal ions from microbial pathogens by releasing metal-chelating proteins such as calprotectin. We show that metal sequestration is detrimental for the accumulation of MBLs in the bacterial periplasm, because those enzymes are readily degraded in their nonmetallated form. However, the New Delhi metallo-β-lactamase (NDM-1) can persist under conditions of metal depletion. NDM-1 is a lipidated protein that anchors to the outer membrane of Gram-negative bacteria. Membrane anchoring contributes to the unusual stability of NDM-1 and favors secretion of this enzyme in outer-membrane vesicles (OMVs). OMVs containing NDM-1 can protect nearby populations of bacteria from otherwise lethal antibiotic levels, and OMVs from clinical pathogens expressing NDM-1 can carry this MBL and the blaNDM gene. We show that protein export into OMVs can be targeted, providing possibilities of new antibacterial therapeutic strategies.
Fil: Gonzalez, Lisandro Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Biológica. Área Biofísica; Argentina
Fil: Bahr, Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Biológica. Área Biofísica; Argentina
Fil: Nakashige, Toshiki G.. Massachusetts Institute of Technology; Estados Unidos
Fil: Nolan, Elizabeth M.. Massachusetts Institute of Technology; Estados Unidos
Fil: Bonomo, Robert A.. Louis Stokes Cleveland Department of Veterans Affairs Medical Center; Estados Unidos. Case Western Reserve University; Estados Unidos
Fil: Vila, Alejandro Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Biológica. Área Biofísica; Argentina
Materia
Ndm-1
Metallo-Beta-Lactamase
Carbapenemase
Beta-Lactam Antibiotic
Membrane Anchoring
Outer Membrane Vesicles
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/52885
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/52885
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Membrane anchoring stabilizes and favors secretion of New Delhi metallo-β-lactamaseGonzalez, Lisandro JavierBahr, GuillermoNakashige, Toshiki G.Nolan, Elizabeth M.Bonomo, Robert A.Vila, Alejandro JoseNdm-1Metallo-Beta-LactamaseCarbapenemaseBeta-Lactam AntibioticMembrane AnchoringOuter Membrane Vesicleshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Carbapenems, 'last-resort' β-lactam antibiotics, are inactivated by zinc-dependent metallo-β-lactamases (MBLs). The host innate immune response withholds nutrient metal ions from microbial pathogens by releasing metal-chelating proteins such as calprotectin. We show that metal sequestration is detrimental for the accumulation of MBLs in the bacterial periplasm, because those enzymes are readily degraded in their nonmetallated form. However, the New Delhi metallo-β-lactamase (NDM-1) can persist under conditions of metal depletion. NDM-1 is a lipidated protein that anchors to the outer membrane of Gram-negative bacteria. Membrane anchoring contributes to the unusual stability of NDM-1 and favors secretion of this enzyme in outer-membrane vesicles (OMVs). OMVs containing NDM-1 can protect nearby populations of bacteria from otherwise lethal antibiotic levels, and OMVs from clinical pathogens expressing NDM-1 can carry this MBL and the blaNDM gene. We show that protein export into OMVs can be targeted, providing possibilities of new antibacterial therapeutic strategies.Fil: Gonzalez, Lisandro Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Biológica. Área Biofísica; ArgentinaFil: Bahr, Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Biológica. Área Biofísica; ArgentinaFil: Nakashige, Toshiki G.. Massachusetts Institute of Technology; Estados UnidosFil: Nolan, Elizabeth M.. Massachusetts Institute of Technology; Estados UnidosFil: Bonomo, Robert A.. Louis Stokes Cleveland Department of Veterans Affairs Medical Center; Estados Unidos. Case Western Reserve University; Estados UnidosFil: Vila, Alejandro Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Biológica. Área Biofísica; ArgentinaNature Publishing Group2016-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/52885Gonzalez, Lisandro Javier; Bahr, Guillermo; Nakashige, Toshiki G.; Nolan, Elizabeth M.; Bonomo, Robert A.; et al.; Membrane anchoring stabilizes and favors secretion of New Delhi metallo-β-lactamase; Nature Publishing Group; Nature Chemical Biology; 12; 7; 7-2016; 516-5221552-4450CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1038/nchembio.2083info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/nchembio.2083info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4912412/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:57:44Zoai:ri.conicet.gov.ar:11336/52885instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:57:44.743CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Membrane anchoring stabilizes and favors secretion of New Delhi metallo-β-lactamase
title Membrane anchoring stabilizes and favors secretion of New Delhi metallo-β-lactamase
spellingShingle Membrane anchoring stabilizes and favors secretion of New Delhi metallo-β-lactamase
Gonzalez, Lisandro Javier
Ndm-1
Metallo-Beta-Lactamase
Carbapenemase
Beta-Lactam Antibiotic
Membrane Anchoring
Outer Membrane Vesicles
title_short Membrane anchoring stabilizes and favors secretion of New Delhi metallo-β-lactamase
title_full Membrane anchoring stabilizes and favors secretion of New Delhi metallo-β-lactamase
title_fullStr Membrane anchoring stabilizes and favors secretion of New Delhi metallo-β-lactamase
title_full_unstemmed Membrane anchoring stabilizes and favors secretion of New Delhi metallo-β-lactamase
title_sort Membrane anchoring stabilizes and favors secretion of New Delhi metallo-β-lactamase
dc.creator.none.fl_str_mv Gonzalez, Lisandro Javier
Bahr, Guillermo
Nakashige, Toshiki G.
Nolan, Elizabeth M.
Bonomo, Robert A.
Vila, Alejandro Jose
author Gonzalez, Lisandro Javier
author_facet Gonzalez, Lisandro Javier
Bahr, Guillermo
Nakashige, Toshiki G.
Nolan, Elizabeth M.
Bonomo, Robert A.
Vila, Alejandro Jose
author_role author
author2 Bahr, Guillermo
Nakashige, Toshiki G.
Nolan, Elizabeth M.
Bonomo, Robert A.
Vila, Alejandro Jose
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Ndm-1
Metallo-Beta-Lactamase
Carbapenemase
Beta-Lactam Antibiotic
Membrane Anchoring
Outer Membrane Vesicles
topic Ndm-1
Metallo-Beta-Lactamase
Carbapenemase
Beta-Lactam Antibiotic
Membrane Anchoring
Outer Membrane Vesicles
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Carbapenems, 'last-resort' β-lactam antibiotics, are inactivated by zinc-dependent metallo-β-lactamases (MBLs). The host innate immune response withholds nutrient metal ions from microbial pathogens by releasing metal-chelating proteins such as calprotectin. We show that metal sequestration is detrimental for the accumulation of MBLs in the bacterial periplasm, because those enzymes are readily degraded in their nonmetallated form. However, the New Delhi metallo-β-lactamase (NDM-1) can persist under conditions of metal depletion. NDM-1 is a lipidated protein that anchors to the outer membrane of Gram-negative bacteria. Membrane anchoring contributes to the unusual stability of NDM-1 and favors secretion of this enzyme in outer-membrane vesicles (OMVs). OMVs containing NDM-1 can protect nearby populations of bacteria from otherwise lethal antibiotic levels, and OMVs from clinical pathogens expressing NDM-1 can carry this MBL and the blaNDM gene. We show that protein export into OMVs can be targeted, providing possibilities of new antibacterial therapeutic strategies.
Fil: Gonzalez, Lisandro Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Biológica. Área Biofísica; Argentina
Fil: Bahr, Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Biológica. Área Biofísica; Argentina
Fil: Nakashige, Toshiki G.. Massachusetts Institute of Technology; Estados Unidos
Fil: Nolan, Elizabeth M.. Massachusetts Institute of Technology; Estados Unidos
Fil: Bonomo, Robert A.. Louis Stokes Cleveland Department of Veterans Affairs Medical Center; Estados Unidos. Case Western Reserve University; Estados Unidos
Fil: Vila, Alejandro Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Biológica. Área Biofísica; Argentina
description Carbapenems, 'last-resort' β-lactam antibiotics, are inactivated by zinc-dependent metallo-β-lactamases (MBLs). The host innate immune response withholds nutrient metal ions from microbial pathogens by releasing metal-chelating proteins such as calprotectin. We show that metal sequestration is detrimental for the accumulation of MBLs in the bacterial periplasm, because those enzymes are readily degraded in their nonmetallated form. However, the New Delhi metallo-β-lactamase (NDM-1) can persist under conditions of metal depletion. NDM-1 is a lipidated protein that anchors to the outer membrane of Gram-negative bacteria. Membrane anchoring contributes to the unusual stability of NDM-1 and favors secretion of this enzyme in outer-membrane vesicles (OMVs). OMVs containing NDM-1 can protect nearby populations of bacteria from otherwise lethal antibiotic levels, and OMVs from clinical pathogens expressing NDM-1 can carry this MBL and the blaNDM gene. We show that protein export into OMVs can be targeted, providing possibilities of new antibacterial therapeutic strategies.
publishDate 2016
dc.date.none.fl_str_mv 2016-07
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/52885
Gonzalez, Lisandro Javier; Bahr, Guillermo; Nakashige, Toshiki G.; Nolan, Elizabeth M.; Bonomo, Robert A.; et al.; Membrane anchoring stabilizes and favors secretion of New Delhi metallo-β-lactamase; Nature Publishing Group; Nature Chemical Biology; 12; 7; 7-2016; 516-522
1552-4450
CONICET Digital
CONICET
url http://hdl.handle.net/11336/52885
identifier_str_mv Gonzalez, Lisandro Javier; Bahr, Guillermo; Nakashige, Toshiki G.; Nolan, Elizabeth M.; Bonomo, Robert A.; et al.; Membrane anchoring stabilizes and favors secretion of New Delhi metallo-β-lactamase; Nature Publishing Group; Nature Chemical Biology; 12; 7; 7-2016; 516-522
1552-4450
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1038/nchembio.2083
info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/nchembio.2083
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4912412/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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