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

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,...

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Autores principales: Le, Casin, Pimentel, Camila, Pasteran, Fernando, Tuttobene, Marisel Romina, Subils, Tomás, Escalante, Jenny, Nishimura, Brent, Arriaga, Susana, Carranza, Aimee, Mezcord, Vyanka, Vila, Alejandro J., Corso, Alejandra, Actis, Luis A., Tolmasky, Marcelo E., Bonomo, Robert A., Ramírez, María Soledad
Formato: article artículo publishedVersion
Lenguaje:Inglés
Publicado: MDPI 2022
Materias:
Acinetobacter baumannii
Cefiderocol
Human fluids
Iron
Human serum albumin
Acceso en línea:http://hdl.handle.net/2133/23635
http://hdl.handle.net/2133/23635
Aporte de:
Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR) de Universidad Nacional de Rosario
id I15-R121-2133-23635
record_format dspace
institution Universidad Nacional de Rosario
institution_str I-15
repository_str R-121
collection Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR)
language Inglés
orig_language_str_mv eng
topic Acinetobacter baumannii
Cefiderocol
Human fluids
Iron
Human serum albumin
spellingShingle Acinetobacter baumannii
Cefiderocol
Human fluids
Iron
Human serum albumin
Le, Casin
Pimentel, Camila
Pasteran, Fernando
Tuttobene, Marisel Romina
Subils, Tomás
Escalante, Jenny
Nishimura, Brent
Arriaga, Susana
Carranza, Aimee
Mezcord, Vyanka
Vila, Alejandro J.
Corso, Alejandra
Actis, Luis A.
Tolmasky, Marcelo E.
Bonomo, Robert A.
Ramírez, María Soledad
Human Serum Proteins and Susceptibility of Acinetobacter baumannii to Cefiderocol: Role of Iron Transport
topic_facet Acinetobacter baumannii
Cefiderocol
Human fluids
Iron
Human serum albumin
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.
format article
artículo
publishedVersion
author Le, Casin
Pimentel, Camila
Pasteran, Fernando
Tuttobene, Marisel Romina
Subils, Tomás
Escalante, Jenny
Nishimura, Brent
Arriaga, Susana
Carranza, Aimee
Mezcord, Vyanka
Vila, Alejandro J.
Corso, Alejandra
Actis, Luis A.
Tolmasky, Marcelo E.
Bonomo, Robert A.
Ramírez, María Soledad
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 J.
Corso, Alejandra
Actis, Luis A.
Tolmasky, Marcelo E.
Bonomo, Robert A.
Ramírez, María Soledad
author_sort Le, Casin
title Human Serum Proteins and Susceptibility of Acinetobacter baumannii to Cefiderocol: Role of Iron Transport
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
publisher MDPI
publishDate 2022
url http://hdl.handle.net/2133/23635
http://hdl.handle.net/2133/23635
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