OXA β-lactamases from Acinetobacter spp. are membrane bound and secreted into outer membrane vesicles

Autores
Capodimonte, Lucía Soledad; Teixeira Pinto Meireles, Fernando; Bahr, Guillermo; Bonomo, Robert A.; Dal Peraro, Matteo; López, María Carolina; Vila, Alejandro Jose
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
β-lactamases from Gram-negative bacteria are generally regarded as soluble, periplasmic enzymes. NDMs have been exceptionally characterized as lipoproteins anchored to the outer membrane. A bioinformatics study on all sequenced β-lactamases was performed that revealed a predominance of putative lipidated enzymes in the Class D OXAs. Namely, 60% of the OXA Class D enzymes contain a lipobox sequence in their signal peptide, that is expected to trigger lipidation and membrane anchoring. This contrasts with β-lactamases from other classes, which are predicted to be mostly soluble proteins. Almost all (>99%) putative lipidated OXAs are present in Acinetobacter spp. Importantly, we further demonstrate that OXA-23 and OXA-24/40 are lipidated, membrane-bound proteins in Acinetobacter baumannii. In contrast, OXA-48 (commonly produced by Enterobacterales) lacks a lipobox and is a soluble protein. Outer membrane vesicles (OMVs) from A. baumannii cells expressing OXA-23 and OXA-24/40 contain these enzymes in their active form. Moreover, OXA-loaded OMVs were able to protect A. baumannii, Escherichia coli, and Pseudomonas aeruginosa cells susceptible to piperacillin and imipenem. These results permit us to conclude that membrane binding is a bacterial host-specific phenomenon in OXA enzymes. These findings reveal that membrane-bound β-lactamases are more common than expected and support the hypothesis that OMVs loaded with lipidated β-lactamases are vehicles for antimicrobial resistance and its dissemination. This advantage could be crucial in polymicrobial infections, in which Acinetobacter spp. are usually involved, and underscore the relevance of identifying the cellular localization of lactamases to better understand their physiology and target them.
Fil: Capodimonte, Lucía Soledad. 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
Fil: Teixeira Pinto Meireles, Fernando. Ecole Polytechnique Federale de Lausanne; Francia
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
Fil: Bonomo, Robert A.. Case Western Reserve University; Estados Unidos
Fil: Dal Peraro, Matteo. Ecole Polytechnique Federale de Lausanne; Francia
Fil: López, María Carolina. 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
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
Materia
ACINETOBACTER SPP.
OXA BETA-LACTAMASES
DISSEMINATION OF ANTIMICROBIAL RESISTANCE
LIPIDATED BETA-LACTAMASES
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:11336/263133
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/263133
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling OXA β-lactamases from Acinetobacter spp. are membrane bound and secreted into outer membrane vesiclesCapodimonte, Lucía SoledadTeixeira Pinto Meireles, FernandoBahr, GuillermoBonomo, Robert A.Dal Peraro, MatteoLópez, María CarolinaVila, Alejandro JoseACINETOBACTER SPP.OXA BETA-LACTAMASESDISSEMINATION OF ANTIMICROBIAL RESISTANCELIPIDATED BETA-LACTAMASESOUTER MEMBRANE VESICLEShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1β-lactamases from Gram-negative bacteria are generally regarded as soluble, periplasmic enzymes. NDMs have been exceptionally characterized as lipoproteins anchored to the outer membrane. A bioinformatics study on all sequenced β-lactamases was performed that revealed a predominance of putative lipidated enzymes in the Class D OXAs. Namely, 60% of the OXA Class D enzymes contain a lipobox sequence in their signal peptide, that is expected to trigger lipidation and membrane anchoring. This contrasts with β-lactamases from other classes, which are predicted to be mostly soluble proteins. Almost all (>99%) putative lipidated OXAs are present in Acinetobacter spp. Importantly, we further demonstrate that OXA-23 and OXA-24/40 are lipidated, membrane-bound proteins in Acinetobacter baumannii. In contrast, OXA-48 (commonly produced by Enterobacterales) lacks a lipobox and is a soluble protein. Outer membrane vesicles (OMVs) from A. baumannii cells expressing OXA-23 and OXA-24/40 contain these enzymes in their active form. Moreover, OXA-loaded OMVs were able to protect A. baumannii, Escherichia coli, and Pseudomonas aeruginosa cells susceptible to piperacillin and imipenem. These results permit us to conclude that membrane binding is a bacterial host-specific phenomenon in OXA enzymes. These findings reveal that membrane-bound β-lactamases are more common than expected and support the hypothesis that OMVs loaded with lipidated β-lactamases are vehicles for antimicrobial resistance and its dissemination. This advantage could be crucial in polymicrobial infections, in which Acinetobacter spp. are usually involved, and underscore the relevance of identifying the cellular localization of lactamases to better understand their physiology and target them.Fil: Capodimonte, Lucía Soledad. 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; ArgentinaFil: Teixeira Pinto Meireles, Fernando. Ecole Polytechnique Federale de Lausanne; FranciaFil: 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; ArgentinaFil: Bonomo, Robert A.. Case Western Reserve University; Estados UnidosFil: Dal Peraro, Matteo. Ecole Polytechnique Federale de Lausanne; FranciaFil: López, María Carolina. 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; ArgentinaFil: 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; ArgentinaAmerican Society for Microbiology2024-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/263133Capodimonte, Lucía Soledad; Teixeira Pinto Meireles, Fernando; Bahr, Guillermo; Bonomo, Robert A.; Dal Peraro, Matteo; et al.; OXA β-lactamases from Acinetobacter spp. are membrane bound and secreted into outer membrane vesicles; American Society for Microbiology; mBio; 16; 2; 12-2024; 1-192150-7511CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://journals.asm.org/doi/10.1128/mbio.03343-24info:eu-repo/semantics/altIdentifier/doi/10.1128/mbio.03343-24info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:57:56Zoai:ri.conicet.gov.ar:11336/263133instacron: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 09:57:56.408CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv OXA β-lactamases from Acinetobacter spp. are membrane bound and secreted into outer membrane vesicles
title OXA β-lactamases from Acinetobacter spp. are membrane bound and secreted into outer membrane vesicles
spellingShingle OXA β-lactamases from Acinetobacter spp. are membrane bound and secreted into outer membrane vesicles
Capodimonte, Lucía Soledad
ACINETOBACTER SPP.
OXA BETA-LACTAMASES
DISSEMINATION OF ANTIMICROBIAL RESISTANCE
LIPIDATED BETA-LACTAMASES
OUTER MEMBRANE VESICLES
title_short OXA β-lactamases from Acinetobacter spp. are membrane bound and secreted into outer membrane vesicles
title_full OXA β-lactamases from Acinetobacter spp. are membrane bound and secreted into outer membrane vesicles
title_fullStr OXA β-lactamases from Acinetobacter spp. are membrane bound and secreted into outer membrane vesicles
title_full_unstemmed OXA β-lactamases from Acinetobacter spp. are membrane bound and secreted into outer membrane vesicles
title_sort OXA β-lactamases from Acinetobacter spp. are membrane bound and secreted into outer membrane vesicles
dc.creator.none.fl_str_mv Capodimonte, Lucía Soledad
Teixeira Pinto Meireles, Fernando
Bahr, Guillermo
Bonomo, Robert A.
Dal Peraro, Matteo
López, María Carolina
Vila, Alejandro Jose
author Capodimonte, Lucía Soledad
author_facet Capodimonte, Lucía Soledad
Teixeira Pinto Meireles, Fernando
Bahr, Guillermo
Bonomo, Robert A.
Dal Peraro, Matteo
López, María Carolina
Vila, Alejandro Jose
author_role author
author2 Teixeira Pinto Meireles, Fernando
Bahr, Guillermo
Bonomo, Robert A.
Dal Peraro, Matteo
López, María Carolina
Vila, Alejandro Jose
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv ACINETOBACTER SPP.
OXA BETA-LACTAMASES
DISSEMINATION OF ANTIMICROBIAL RESISTANCE
LIPIDATED BETA-LACTAMASES
OUTER MEMBRANE VESICLES
topic ACINETOBACTER SPP.
OXA BETA-LACTAMASES
DISSEMINATION OF ANTIMICROBIAL RESISTANCE
LIPIDATED BETA-LACTAMASES
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 β-lactamases from Gram-negative bacteria are generally regarded as soluble, periplasmic enzymes. NDMs have been exceptionally characterized as lipoproteins anchored to the outer membrane. A bioinformatics study on all sequenced β-lactamases was performed that revealed a predominance of putative lipidated enzymes in the Class D OXAs. Namely, 60% of the OXA Class D enzymes contain a lipobox sequence in their signal peptide, that is expected to trigger lipidation and membrane anchoring. This contrasts with β-lactamases from other classes, which are predicted to be mostly soluble proteins. Almost all (>99%) putative lipidated OXAs are present in Acinetobacter spp. Importantly, we further demonstrate that OXA-23 and OXA-24/40 are lipidated, membrane-bound proteins in Acinetobacter baumannii. In contrast, OXA-48 (commonly produced by Enterobacterales) lacks a lipobox and is a soluble protein. Outer membrane vesicles (OMVs) from A. baumannii cells expressing OXA-23 and OXA-24/40 contain these enzymes in their active form. Moreover, OXA-loaded OMVs were able to protect A. baumannii, Escherichia coli, and Pseudomonas aeruginosa cells susceptible to piperacillin and imipenem. These results permit us to conclude that membrane binding is a bacterial host-specific phenomenon in OXA enzymes. These findings reveal that membrane-bound β-lactamases are more common than expected and support the hypothesis that OMVs loaded with lipidated β-lactamases are vehicles for antimicrobial resistance and its dissemination. This advantage could be crucial in polymicrobial infections, in which Acinetobacter spp. are usually involved, and underscore the relevance of identifying the cellular localization of lactamases to better understand their physiology and target them.
Fil: Capodimonte, Lucía Soledad. 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
Fil: Teixeira Pinto Meireles, Fernando. Ecole Polytechnique Federale de Lausanne; Francia
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
Fil: Bonomo, Robert A.. Case Western Reserve University; Estados Unidos
Fil: Dal Peraro, Matteo. Ecole Polytechnique Federale de Lausanne; Francia
Fil: López, María Carolina. 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
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
description β-lactamases from Gram-negative bacteria are generally regarded as soluble, periplasmic enzymes. NDMs have been exceptionally characterized as lipoproteins anchored to the outer membrane. A bioinformatics study on all sequenced β-lactamases was performed that revealed a predominance of putative lipidated enzymes in the Class D OXAs. Namely, 60% of the OXA Class D enzymes contain a lipobox sequence in their signal peptide, that is expected to trigger lipidation and membrane anchoring. This contrasts with β-lactamases from other classes, which are predicted to be mostly soluble proteins. Almost all (>99%) putative lipidated OXAs are present in Acinetobacter spp. Importantly, we further demonstrate that OXA-23 and OXA-24/40 are lipidated, membrane-bound proteins in Acinetobacter baumannii. In contrast, OXA-48 (commonly produced by Enterobacterales) lacks a lipobox and is a soluble protein. Outer membrane vesicles (OMVs) from A. baumannii cells expressing OXA-23 and OXA-24/40 contain these enzymes in their active form. Moreover, OXA-loaded OMVs were able to protect A. baumannii, Escherichia coli, and Pseudomonas aeruginosa cells susceptible to piperacillin and imipenem. These results permit us to conclude that membrane binding is a bacterial host-specific phenomenon in OXA enzymes. These findings reveal that membrane-bound β-lactamases are more common than expected and support the hypothesis that OMVs loaded with lipidated β-lactamases are vehicles for antimicrobial resistance and its dissemination. This advantage could be crucial in polymicrobial infections, in which Acinetobacter spp. are usually involved, and underscore the relevance of identifying the cellular localization of lactamases to better understand their physiology and target them.
publishDate 2024
dc.date.none.fl_str_mv 2024-12
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/11336/263133
Capodimonte, Lucía Soledad; Teixeira Pinto Meireles, Fernando; Bahr, Guillermo; Bonomo, Robert A.; Dal Peraro, Matteo; et al.; OXA β-lactamases from Acinetobacter spp. are membrane bound and secreted into outer membrane vesicles; American Society for Microbiology; mBio; 16; 2; 12-2024; 1-19
2150-7511
CONICET Digital
CONICET
url http://hdl.handle.net/11336/263133
identifier_str_mv Capodimonte, Lucía Soledad; Teixeira Pinto Meireles, Fernando; Bahr, Guillermo; Bonomo, Robert A.; Dal Peraro, Matteo; et al.; OXA β-lactamases from Acinetobacter spp. are membrane bound and secreted into outer membrane vesicles; American Society for Microbiology; mBio; 16; 2; 12-2024; 1-19
2150-7511
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://journals.asm.org/doi/10.1128/mbio.03343-24
info:eu-repo/semantics/altIdentifier/doi/10.1128/mbio.03343-24
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
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: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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score 13.13397

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