The Iron Content of Human Serum Albumin Modulates the Susceptibility of Acinetobacter baumannii to Cefiderocol

The mortality rates of patients infected with Acinetobacter baumannii who were treated with cefiderocol (CFDC) were not as favorable as those receiving the best available treatment for pulmonary and bloodstream infections. Previous studies showed that the presence of human serum albumin (HSA) or...

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Autores principales: Escalante, Jenny, Nishimura, Brent, Tuttobene, Marisel Romina, Subils, Tomás, Mezcord, Vyanka, Actis, Luis A., Tolmasky, Marcelo E., Bonomo, Robert A., Ramírez, María Soledad
Formato: article artículo publishedVersion
Lenguaje:Inglés
Publicado: MDPI 2023
Materias:
Acceso en línea:http://hdl.handle.net/2133/25434
http://hdl.handle.net/2133/25434
Aporte de:
id I15-R121-2133-25434
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
topic Acinetobacter baumannii
Human serum albumin
Cefiderocol
Iron
Human pleural fluid
Carbapenem resistance
spellingShingle Acinetobacter baumannii
Human serum albumin
Cefiderocol
Iron
Human pleural fluid
Carbapenem resistance
Escalante, Jenny
Nishimura, Brent
Tuttobene, Marisel Romina
Subils, Tomás
Mezcord, Vyanka
Actis, Luis A.
Tolmasky, Marcelo E.
Bonomo, Robert A.
Ramírez, María Soledad
The Iron Content of Human Serum Albumin Modulates the Susceptibility of Acinetobacter baumannii to Cefiderocol
topic_facet Acinetobacter baumannii
Human serum albumin
Cefiderocol
Iron
Human pleural fluid
Carbapenem resistance
description The mortality rates of patients infected with Acinetobacter baumannii who were treated with cefiderocol (CFDC) were not as favorable as those receiving the best available treatment for pulmonary and bloodstream infections. Previous studies showed that the presence of human serum albumin (HSA) or HSA-containing fluids, such as human serum (HS) or human pleural fluid (HPF), in the growth medium is correlated with a decrease in the expression of genes associated with highaffinity siderophore-mediated iron uptake systems. These observations may explain the complexities of the observed clinical performance of CFDC in pulmonary and bloodstream infections, because ferric siderophore transporters enhance the penetration of CFDC into the bacterial cell. The removal of HSA from HS or HPF resulted in a reduction in the minimal inhibitory concentration (MIC) of CFDC. Concomitant with these results, an enhancement in the expression of TonB-dependent transporters known to play a crucial role in transporting iron was observed. In addition to inducing modifications in iron-uptake gene expression, the removal of HSA also decreased the expression of β-lactamases genes. Taken together, these observations suggest that environmental HSA has a role in the expression levels of select A. baumannii genes. Furthermore, the removal of iron from HSA had the same effect as the removal of HSA upon the expression of genes associated with iron uptake systems, also suggesting that at least one of the mechanisms by which HSA regulates the expression of certain genes is through acting as an iron source.
format article
artículo
publishedVersion
author Escalante, Jenny
Nishimura, Brent
Tuttobene, Marisel Romina
Subils, Tomás
Mezcord, Vyanka
Actis, Luis A.
Tolmasky, Marcelo E.
Bonomo, Robert A.
Ramírez, María Soledad
author_facet Escalante, Jenny
Nishimura, Brent
Tuttobene, Marisel Romina
Subils, Tomás
Mezcord, Vyanka
Actis, Luis A.
Tolmasky, Marcelo E.
Bonomo, Robert A.
Ramírez, María Soledad
author_sort Escalante, Jenny
title The Iron Content of Human Serum Albumin Modulates the Susceptibility of Acinetobacter baumannii to Cefiderocol
title_short The Iron Content of Human Serum Albumin Modulates the Susceptibility of Acinetobacter baumannii to Cefiderocol
title_full The Iron Content of Human Serum Albumin Modulates the Susceptibility of Acinetobacter baumannii to Cefiderocol
title_fullStr The Iron Content of Human Serum Albumin Modulates the Susceptibility of Acinetobacter baumannii to Cefiderocol
title_full_unstemmed The Iron Content of Human Serum Albumin Modulates the Susceptibility of Acinetobacter baumannii to Cefiderocol
title_sort iron content of human serum albumin modulates the susceptibility of acinetobacter baumannii to cefiderocol
publisher MDPI
publishDate 2023
url http://hdl.handle.net/2133/25434
http://hdl.handle.net/2133/25434
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