Human Serum Proteins and Susceptibility of Acinetobacter baumannii to Cefiderocol: Role of Iron Transport

Autores
Le, Casin; Pimentel, Camila; Pasteran, Fernando; Tuttobene, Marisel Romina; Subils, Tomás; Escalante, Jenny; Nishimura, Brent; Arriaga, Susana; Carranza, Aimee; Mezcord, Vyanka; Vila, Alejandro Jose; Corso, Alejandra; Actis, Luis A.; Tolmasky, Marcelo E.; Bonomo, Robert A.; Ramírez, Maria Soledad
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Cefiderocol, a recently introduced antibiotic, has a chemical structure that includes a cephalosporin that targets cell wall synthesis and a chlorocatechol siderophore moiety that facilitates cell penetration by active iron transporters. Analysis of the effect that human serum, human serum albumin, and human pleural fluid had on growing Acinetobacter baumannii showed that genes related to iron uptake were down-regulated. At the same time, β-lactamase genes were expressed at higher levels. The minimum inhibitory concentrations of this antimicrobial in A. baumannii cells growing in the presence of human serum, human serum albumin, or human pleural fluid were higher than those measured when these fluids were absent from the culture medium. These results correlate with increased expression levels of β-lactamase genes and the down-regulation of iron uptake-related genes in cultures containing human serum, human serum albumin, or human pleural fluid. These modifications in gene expression could explain the less-than-ideal clinical response observed in patients with pulmonary or bloodstream A. baumannii infections. The exposure of the infecting cells to the host’s fluids could cause reduced cefiderocol transport capabilities and increased resistance to β-lactams. The regulation of genes that could impact the A. baumannii susceptibility to cefiderocol, or other antibacterials, is an understudied phenomenon that merits further investigation.
Fil: Le, Casin. University of California; Estados Unidos
Fil: Pimentel, Camila. University of California; Estados Unidos
Fil: Pasteran, Fernando. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. 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: Subils, Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Procesos Biotecnológicos y Químicos Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Procesos Biotecnológicos y Químicos Rosario; Argentina
Fil: Escalante, Jenny. University of California; Estados Unidos
Fil: Nishimura, Brent. University of California; Estados Unidos
Fil: Arriaga, Susana. University of California; Estados Unidos
Fil: Carranza, Aimee. University of California; Estados Unidos
Fil: Mezcord, Vyanka. University of California; 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
Fil: Corso, Alejandra. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; Argentina
Fil: Actis, Luis A.. Miami University; Estados Unidos
Fil: Tolmasky, Marcelo E.. University of California; Estados Unidos
Fil: Bonomo, Robert A.. No especifíca;
Fil: Ramírez, Maria Soledad. University of California; Estados Unidos
Materia
ACINETOBACTER BAUMANNII
CEFIDEROCOL
HUMAN FLUIDS
HUMAN SERUM ALBUMIN
IRON
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/211034
Acceder
id CONICETDig_10c3b8b0fdb7148040354581bb32f69c
oai_identifier_str oai:ri.conicet.gov.ar:11336/211034
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Human Serum Proteins and Susceptibility of Acinetobacter baumannii to Cefiderocol: Role of Iron TransportLe, CasinPimentel, CamilaPasteran, FernandoTuttobene, Marisel RominaSubils, TomásEscalante, JennyNishimura, BrentArriaga, SusanaCarranza, AimeeMezcord, VyankaVila, Alejandro JoseCorso, AlejandraActis, Luis A.Tolmasky, Marcelo E.Bonomo, Robert A.Ramírez, Maria SoledadACINETOBACTER BAUMANNIICEFIDEROCOLHUMAN FLUIDSHUMAN SERUM ALBUMINIRONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Cefiderocol, a recently introduced antibiotic, has a chemical structure that includes a cephalosporin that targets cell wall synthesis and a chlorocatechol siderophore moiety that facilitates cell penetration by active iron transporters. Analysis of the effect that human serum, human serum albumin, and human pleural fluid had on growing Acinetobacter baumannii showed that genes related to iron uptake were down-regulated. At the same time, β-lactamase genes were expressed at higher levels. The minimum inhibitory concentrations of this antimicrobial in A. baumannii cells growing in the presence of human serum, human serum albumin, or human pleural fluid were higher than those measured when these fluids were absent from the culture medium. These results correlate with increased expression levels of β-lactamase genes and the down-regulation of iron uptake-related genes in cultures containing human serum, human serum albumin, or human pleural fluid. These modifications in gene expression could explain the less-than-ideal clinical response observed in patients with pulmonary or bloodstream A. baumannii infections. The exposure of the infecting cells to the host’s fluids could cause reduced cefiderocol transport capabilities and increased resistance to β-lactams. The regulation of genes that could impact the A. baumannii susceptibility to cefiderocol, or other antibacterials, is an understudied phenomenon that merits further investigation.Fil: Le, Casin. University of California; Estados UnidosFil: Pimentel, Camila. University of California; Estados UnidosFil: Pasteran, Fernando. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. 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: Subils, Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Procesos Biotecnológicos y Químicos Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Procesos Biotecnológicos y Químicos Rosario; ArgentinaFil: Escalante, Jenny. University of California; Estados UnidosFil: Nishimura, Brent. University of California; Estados UnidosFil: Arriaga, Susana. University of California; Estados UnidosFil: Carranza, Aimee. University of California; Estados UnidosFil: Mezcord, Vyanka. University of California; 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; ArgentinaFil: Corso, Alejandra. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; ArgentinaFil: Actis, Luis A.. Miami University; Estados UnidosFil: Tolmasky, Marcelo E.. University of California; Estados UnidosFil: Bonomo, Robert A.. No especifíca;Fil: Ramírez, Maria Soledad. University of California; Estados UnidosMDPI2022-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/211034Le, Casin; Pimentel, Camila; Pasteran, Fernando; Tuttobene, Marisel Romina; Subils, Tomás; et al.; Human Serum Proteins and Susceptibility of Acinetobacter baumannii to Cefiderocol: Role of Iron Transport; MDPI; Biomedicines; 10; 3; 3-2022; 1-122227-9059CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2227-9059/10/3/600info:eu-repo/semantics/altIdentifier/doi/10.3390/biomedicines10030600info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:46:25Zoai:ri.conicet.gov.ar:11336/211034instacron: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 09:46:25.486CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Human Serum Proteins and Susceptibility of Acinetobacter baumannii to Cefiderocol: Role of Iron Transport
title Human Serum Proteins and Susceptibility of Acinetobacter baumannii to Cefiderocol: Role of Iron Transport
spellingShingle Human Serum Proteins and Susceptibility of Acinetobacter baumannii to Cefiderocol: Role of Iron Transport
Le, Casin
ACINETOBACTER BAUMANNII
CEFIDEROCOL
HUMAN FLUIDS
HUMAN SERUM ALBUMIN
IRON
title_short Human Serum Proteins and Susceptibility of Acinetobacter baumannii to Cefiderocol: Role of Iron Transport
title_full Human Serum Proteins and Susceptibility of Acinetobacter baumannii to Cefiderocol: Role of Iron Transport
title_fullStr Human Serum Proteins and Susceptibility of Acinetobacter baumannii to Cefiderocol: Role of Iron Transport
title_full_unstemmed Human Serum Proteins and Susceptibility of Acinetobacter baumannii to Cefiderocol: Role of Iron Transport
title_sort Human Serum Proteins and Susceptibility of Acinetobacter baumannii to Cefiderocol: Role of Iron Transport
dc.creator.none.fl_str_mv Le, Casin
Pimentel, Camila
Pasteran, Fernando
Tuttobene, Marisel Romina
Subils, Tomás
Escalante, Jenny
Nishimura, Brent
Arriaga, Susana
Carranza, Aimee
Mezcord, Vyanka
Vila, Alejandro Jose
Corso, Alejandra
Actis, Luis A.
Tolmasky, Marcelo E.
Bonomo, Robert A.
Ramírez, Maria Soledad
author Le, Casin
author_facet Le, Casin
Pimentel, Camila
Pasteran, Fernando
Tuttobene, Marisel Romina
Subils, Tomás
Escalante, Jenny
Nishimura, Brent
Arriaga, Susana
Carranza, Aimee
Mezcord, Vyanka
Vila, Alejandro Jose
Corso, Alejandra
Actis, Luis A.
Tolmasky, Marcelo E.
Bonomo, Robert A.
Ramírez, Maria Soledad
author_role author
author2 Pimentel, Camila
Pasteran, Fernando
Tuttobene, Marisel Romina
Subils, Tomás
Escalante, Jenny
Nishimura, Brent
Arriaga, Susana
Carranza, Aimee
Mezcord, Vyanka
Vila, Alejandro Jose
Corso, Alejandra
Actis, Luis A.
Tolmasky, Marcelo E.
Bonomo, Robert A.
Ramírez, Maria Soledad
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ACINETOBACTER BAUMANNII
CEFIDEROCOL
HUMAN FLUIDS
HUMAN SERUM ALBUMIN
IRON
topic ACINETOBACTER BAUMANNII
CEFIDEROCOL
HUMAN FLUIDS
HUMAN SERUM ALBUMIN
IRON
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 recently introduced antibiotic, has a chemical structure that includes a cephalosporin that targets cell wall synthesis and a chlorocatechol siderophore moiety that facilitates cell penetration by active iron transporters. Analysis of the effect that human serum, human serum albumin, and human pleural fluid had on growing Acinetobacter baumannii showed that genes related to iron uptake were down-regulated. At the same time, β-lactamase genes were expressed at higher levels. The minimum inhibitory concentrations of this antimicrobial in A. baumannii cells growing in the presence of human serum, human serum albumin, or human pleural fluid were higher than those measured when these fluids were absent from the culture medium. These results correlate with increased expression levels of β-lactamase genes and the down-regulation of iron uptake-related genes in cultures containing human serum, human serum albumin, or human pleural fluid. These modifications in gene expression could explain the less-than-ideal clinical response observed in patients with pulmonary or bloodstream A. baumannii infections. The exposure of the infecting cells to the host’s fluids could cause reduced cefiderocol transport capabilities and increased resistance to β-lactams. The regulation of genes that could impact the A. baumannii susceptibility to cefiderocol, or other antibacterials, is an understudied phenomenon that merits further investigation.
Fil: Le, Casin. University of California; Estados Unidos
Fil: Pimentel, Camila. University of California; Estados Unidos
Fil: Pasteran, Fernando. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. 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: Subils, Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Procesos Biotecnológicos y Químicos Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Procesos Biotecnológicos y Químicos Rosario; Argentina
Fil: Escalante, Jenny. University of California; Estados Unidos
Fil: Nishimura, Brent. University of California; Estados Unidos
Fil: Arriaga, Susana. University of California; Estados Unidos
Fil: Carranza, Aimee. University of California; Estados Unidos
Fil: Mezcord, Vyanka. University of California; 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
Fil: Corso, Alejandra. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; Argentina
Fil: Actis, Luis A.. Miami University; Estados Unidos
Fil: Tolmasky, Marcelo E.. University of California; Estados Unidos
Fil: Bonomo, Robert A.. No especifíca;
Fil: Ramírez, Maria Soledad. University of California; Estados Unidos
description Cefiderocol, a recently introduced antibiotic, has a chemical structure that includes a cephalosporin that targets cell wall synthesis and a chlorocatechol siderophore moiety that facilitates cell penetration by active iron transporters. Analysis of the effect that human serum, human serum albumin, and human pleural fluid had on growing Acinetobacter baumannii showed that genes related to iron uptake were down-regulated. At the same time, β-lactamase genes were expressed at higher levels. The minimum inhibitory concentrations of this antimicrobial in A. baumannii cells growing in the presence of human serum, human serum albumin, or human pleural fluid were higher than those measured when these fluids were absent from the culture medium. These results correlate with increased expression levels of β-lactamase genes and the down-regulation of iron uptake-related genes in cultures containing human serum, human serum albumin, or human pleural fluid. These modifications in gene expression could explain the less-than-ideal clinical response observed in patients with pulmonary or bloodstream A. baumannii infections. The exposure of the infecting cells to the host’s fluids could cause reduced cefiderocol transport capabilities and increased resistance to β-lactams. The regulation of genes that could impact the A. baumannii susceptibility to cefiderocol, or other antibacterials, is an understudied phenomenon that merits further investigation.
publishDate 2022
dc.date.none.fl_str_mv 2022-03
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/11336/211034
Le, Casin; Pimentel, Camila; Pasteran, Fernando; Tuttobene, Marisel Romina; Subils, Tomás; et al.; Human Serum Proteins and Susceptibility of Acinetobacter baumannii to Cefiderocol: Role of Iron Transport; MDPI; Biomedicines; 10; 3; 3-2022; 1-12
2227-9059
CONICET Digital
CONICET
url http://hdl.handle.net/11336/211034
identifier_str_mv Le, Casin; Pimentel, Camila; Pasteran, Fernando; Tuttobene, Marisel Romina; Subils, Tomás; et al.; Human Serum Proteins and Susceptibility of Acinetobacter baumannii to Cefiderocol: Role of Iron Transport; MDPI; Biomedicines; 10; 3; 3-2022; 1-12
2227-9059
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://www.mdpi.com/2227-9059/10/3/600
info:eu-repo/semantics/altIdentifier/doi/10.3390/biomedicines10030600
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
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
_version_ 1842268793921863680
score 13.13397

Publicaciones similares