Hetero-antagonism of avibactam and sulbactam with cefiderocol in carbapenem-resistant Acinetobacter spp
- Autores
- Wong, Olivia; Mezcord, Vyanka; Lopez, Christina; Traglia, German Matias; Pasteran, Fernando; Tuttobene, Marisel Romina; Corso, Alejandra; Tolmasky, Marcelo E.; Bonomo, Robert A.; Ramirez, María Soledad
- Año de publicación
- 2024
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Cefiderocol, a siderophore-cephalosporine conjugate antibiotic, shows promise as a therapeutic option for carbapenem-resistant (CR) Acinetobacter infections. While resistance has already been reported in A. baumannii, combination therapies with avibactam or sulbactam reduce MICs of cefiderocol, extending its efficacy. However, careful consideration is necessary when using these combinations. In our experiments, exposure of A. baumannii and A. lwoffii to cefiderocol and sulbactam or avibactam led to the selection of cefiderocol-resistant strains. Three of those were subjected to whole genome sequencing and transcriptomic analysis. The strains all possessed synonymous and non-synonymous substitutions and short deletions. The most significant mutations affected efflux pumps, transcriptional regulators, and iron homeostasis genes. Transcriptomics showed significant alterations in expression levels of outer membrane proteins, iron homeostasis, and β-lactamases, suggesting adaptive responses to selective pressure. This study underscores the importance of carefully assessing drug synergies, as they may inadvertently foster the selection of resistant variants and complicate the management of CR Acinetobacter infections.
Fil: Wong, Olivia. California State University; Estados Unidos
Fil: Mezcord, Vyanka. California State University; Estados Unidos
Fil: Lopez, Christina. California State University; Estados Unidos
Fil: Traglia, German Matias. Universidad de la República; Uruguay
Fil: Pasteran, Fernando. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; Argentina
Fil: Tuttobene, Marisel Romina. 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: Corso, Alejandra. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; Argentina
Fil: Tolmasky, Marcelo E.. California State University; Estados Unidos
Fil: Bonomo, Robert A.. No especifíca;
Fil: Ramirez, María Soledad. California State University; Estados Unidos - Materia
-
ACINETOBACTER BAUMANNII
CEFIDEROCOL
AVIBACTAM - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/266347
Ver los metadatos del registro completo
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oai:ri.conicet.gov.ar:11336/266347 |
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3498 |
network_name_str |
CONICET Digital (CONICET) |
spelling |
Hetero-antagonism of avibactam and sulbactam with cefiderocol in carbapenem-resistant Acinetobacter sppWong, OliviaMezcord, VyankaLopez, ChristinaTraglia, German MatiasPasteran, FernandoTuttobene, Marisel RominaCorso, AlejandraTolmasky, Marcelo E.Bonomo, Robert A.Ramirez, María SoledadACINETOBACTER BAUMANNIICEFIDEROCOLAVIBACTAMhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Cefiderocol, a siderophore-cephalosporine conjugate antibiotic, shows promise as a therapeutic option for carbapenem-resistant (CR) Acinetobacter infections. While resistance has already been reported in A. baumannii, combination therapies with avibactam or sulbactam reduce MICs of cefiderocol, extending its efficacy. However, careful consideration is necessary when using these combinations. In our experiments, exposure of A. baumannii and A. lwoffii to cefiderocol and sulbactam or avibactam led to the selection of cefiderocol-resistant strains. Three of those were subjected to whole genome sequencing and transcriptomic analysis. The strains all possessed synonymous and non-synonymous substitutions and short deletions. The most significant mutations affected efflux pumps, transcriptional regulators, and iron homeostasis genes. Transcriptomics showed significant alterations in expression levels of outer membrane proteins, iron homeostasis, and β-lactamases, suggesting adaptive responses to selective pressure. This study underscores the importance of carefully assessing drug synergies, as they may inadvertently foster the selection of resistant variants and complicate the management of CR Acinetobacter infections.Fil: Wong, Olivia. California State University; Estados UnidosFil: Mezcord, Vyanka. California State University; Estados UnidosFil: Lopez, Christina. California State University; Estados UnidosFil: Traglia, German Matias. Universidad de la República; UruguayFil: Pasteran, Fernando. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Tuttobene, Marisel Romina. 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: Corso, Alejandra. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Tolmasky, Marcelo E.. California State University; Estados UnidosFil: Bonomo, Robert A.. No especifíca;Fil: Ramirez, María Soledad. California State University; Estados UnidosAmerican Society for Microbiology2024-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/266347Wong, Olivia; Mezcord, Vyanka; Lopez, Christina; Traglia, German Matias; Pasteran, Fernando; et al.; Hetero-antagonism of avibactam and sulbactam with cefiderocol in carbapenem-resistant Acinetobacter spp; American Society for Microbiology; Microbiology Spectrum; 12; 10; 8-2024; 1-112165-0497CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://journals.asm.org/doi/10.1128/spectrum.00930-24info:eu-repo/semantics/altIdentifier/doi/10.1128/spectrum.00930-24info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:51:16Zoai:ri.conicet.gov.ar:11336/266347instacron: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 09:51:16.975CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Hetero-antagonism of avibactam and sulbactam with cefiderocol in carbapenem-resistant Acinetobacter spp |
title |
Hetero-antagonism of avibactam and sulbactam with cefiderocol in carbapenem-resistant Acinetobacter spp |
spellingShingle |
Hetero-antagonism of avibactam and sulbactam with cefiderocol in carbapenem-resistant Acinetobacter spp Wong, Olivia ACINETOBACTER BAUMANNII CEFIDEROCOL AVIBACTAM |
title_short |
Hetero-antagonism of avibactam and sulbactam with cefiderocol in carbapenem-resistant Acinetobacter spp |
title_full |
Hetero-antagonism of avibactam and sulbactam with cefiderocol in carbapenem-resistant Acinetobacter spp |
title_fullStr |
Hetero-antagonism of avibactam and sulbactam with cefiderocol in carbapenem-resistant Acinetobacter spp |
title_full_unstemmed |
Hetero-antagonism of avibactam and sulbactam with cefiderocol in carbapenem-resistant Acinetobacter spp |
title_sort |
Hetero-antagonism of avibactam and sulbactam with cefiderocol in carbapenem-resistant Acinetobacter spp |
dc.creator.none.fl_str_mv |
Wong, Olivia Mezcord, Vyanka Lopez, Christina Traglia, German Matias Pasteran, Fernando Tuttobene, Marisel Romina Corso, Alejandra Tolmasky, Marcelo E. Bonomo, Robert A. Ramirez, María Soledad |
author |
Wong, Olivia |
author_facet |
Wong, Olivia Mezcord, Vyanka Lopez, Christina Traglia, German Matias Pasteran, Fernando Tuttobene, Marisel Romina Corso, Alejandra Tolmasky, Marcelo E. Bonomo, Robert A. Ramirez, María Soledad |
author_role |
author |
author2 |
Mezcord, Vyanka Lopez, Christina Traglia, German Matias Pasteran, Fernando Tuttobene, Marisel Romina Corso, Alejandra Tolmasky, Marcelo E. Bonomo, Robert A. Ramirez, María Soledad |
author2_role |
author author author author author author author author author |
dc.subject.none.fl_str_mv |
ACINETOBACTER BAUMANNII CEFIDEROCOL AVIBACTAM |
topic |
ACINETOBACTER BAUMANNII CEFIDEROCOL AVIBACTAM |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
Cefiderocol, a siderophore-cephalosporine conjugate antibiotic, shows promise as a therapeutic option for carbapenem-resistant (CR) Acinetobacter infections. While resistance has already been reported in A. baumannii, combination therapies with avibactam or sulbactam reduce MICs of cefiderocol, extending its efficacy. However, careful consideration is necessary when using these combinations. In our experiments, exposure of A. baumannii and A. lwoffii to cefiderocol and sulbactam or avibactam led to the selection of cefiderocol-resistant strains. Three of those were subjected to whole genome sequencing and transcriptomic analysis. The strains all possessed synonymous and non-synonymous substitutions and short deletions. The most significant mutations affected efflux pumps, transcriptional regulators, and iron homeostasis genes. Transcriptomics showed significant alterations in expression levels of outer membrane proteins, iron homeostasis, and β-lactamases, suggesting adaptive responses to selective pressure. This study underscores the importance of carefully assessing drug synergies, as they may inadvertently foster the selection of resistant variants and complicate the management of CR Acinetobacter infections. Fil: Wong, Olivia. California State University; Estados Unidos Fil: Mezcord, Vyanka. California State University; Estados Unidos Fil: Lopez, Christina. California State University; Estados Unidos Fil: Traglia, German Matias. Universidad de la República; Uruguay Fil: Pasteran, Fernando. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; Argentina Fil: Tuttobene, Marisel Romina. 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: Corso, Alejandra. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; Argentina Fil: Tolmasky, Marcelo E.. California State University; Estados Unidos Fil: Bonomo, Robert A.. No especifíca; Fil: Ramirez, María Soledad. California State University; Estados Unidos |
description |
Cefiderocol, a siderophore-cephalosporine conjugate antibiotic, shows promise as a therapeutic option for carbapenem-resistant (CR) Acinetobacter infections. While resistance has already been reported in A. baumannii, combination therapies with avibactam or sulbactam reduce MICs of cefiderocol, extending its efficacy. However, careful consideration is necessary when using these combinations. In our experiments, exposure of A. baumannii and A. lwoffii to cefiderocol and sulbactam or avibactam led to the selection of cefiderocol-resistant strains. Three of those were subjected to whole genome sequencing and transcriptomic analysis. The strains all possessed synonymous and non-synonymous substitutions and short deletions. The most significant mutations affected efflux pumps, transcriptional regulators, and iron homeostasis genes. Transcriptomics showed significant alterations in expression levels of outer membrane proteins, iron homeostasis, and β-lactamases, suggesting adaptive responses to selective pressure. This study underscores the importance of carefully assessing drug synergies, as they may inadvertently foster the selection of resistant variants and complicate the management of CR Acinetobacter infections. |
publishDate |
2024 |
dc.date.none.fl_str_mv |
2024-08 |
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/11336/266347 Wong, Olivia; Mezcord, Vyanka; Lopez, Christina; Traglia, German Matias; Pasteran, Fernando; et al.; Hetero-antagonism of avibactam and sulbactam with cefiderocol in carbapenem-resistant Acinetobacter spp; American Society for Microbiology; Microbiology Spectrum; 12; 10; 8-2024; 1-11 2165-0497 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/266347 |
identifier_str_mv |
Wong, Olivia; Mezcord, Vyanka; Lopez, Christina; Traglia, German Matias; Pasteran, Fernando; et al.; Hetero-antagonism of avibactam and sulbactam with cefiderocol in carbapenem-resistant Acinetobacter spp; American Society for Microbiology; Microbiology Spectrum; 12; 10; 8-2024; 1-11 2165-0497 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/spectrum.00930-24 info:eu-repo/semantics/altIdentifier/doi/10.1128/spectrum.00930-24 |
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 |
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 |
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CONICET Digital (CONICET) |
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CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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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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13.13397 |