Please use this identifier to cite or link to this item: http://sgc.anlis.gob.ar/handle/123456789/2511
Title: Human Serum Proteins and Susceptibility of Acinetobacter baumannii to Cefiderocol: Role of Iron Transport
Authors: Le, Casin 
Pimentel, Camila 
Pasteran, Fernando 
Tuttobene, Marisel R 
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 
Ramirez, Maria Soledad 
Keywords: Acinetobacter baumannii;cefiderocol;human fluids;human serum albumin;iron
Issue Date: 3-Mar-2022
Journal: Biomedicines 
Abstract: 
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.
Description: 
Fil: Le, Casin. Center for Applied Biotechnology Studies, Department of Biological Science, College of Natural Sciences and Mathematics, California State University Fullerton; United States

Fil: Pimentel, Camila. Center for Applied Biotechnology Studies, Department of Biological Science, College of Natural Sciences and Mathematics, California State University Fullerton; United States

Fil: Pasteran, Fernando. National/Regional Reference Laboratory for Antimicrobial Resistance (NRL), Servicio Antimicrobianos, Instituto Nacional de Enfermedades Infecciosas, ANLIS Dr. Carlos G. Malbrán; Buenos Aires, Argentina

Fil: Tuttobene, Marisel R. Área Biología Molecular, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario; Rosario, Argentina

Fil: Subils, Tomás. Instituto de Procesos Biotecnológicos y Químicos de Rosario (IPROBYQ, CONICET-UNR); Rosario, Argentina

Fil: Escalante, Jenny. Center for Applied Biotechnology Studies, Department of Biological Science, College of Natural Sciences and Mathematics, California State University Fullerton; United States

Fil: Nishimura, Brent. Center for Applied Biotechnology Studies, Department of Biological Science, College of Natural Sciences and Mathematics, California State University Fullerton; United States

Fil: Arriaga, Susana. Center for Applied Biotechnology Studies, Department of Biological Science, College of Natural Sciences and Mathematics, California State University Fullerton; United States

Fil: Carranza, Aimee. Center for Applied Biotechnology Studies, Department of Biological Science, College of Natural Sciences and Mathematics, California State University Fullerton; United States

Fil: Mezcord, Vyanka. Center for Applied Biotechnology Studies, Department of Biological Science, College of Natural Sciences and Mathematics, California State University Fullerton; United States

Fil: Vila, Alejandro J. Instituto de Biología Molecular y Celular de Rosario (IBR, CONICET-UNR); Rosario, Argentina

Fil: Corso, Alejandra. National/Regional Reference Laboratory for Antimicrobial Resistance (NRL), Servicio Antimicrobianos, Instituto Nacional de Enfermedades Infecciosas, ANLIS Dr. Carlos G. Malbrán; Buenos Aires, Argentina

Fil: Actis, Luis A. Department of Microbiology, Miami University; United States

Fil: Tolmasky, Marcelo E. Center for Applied Biotechnology Studies, Department of Biological Science, College of Natural Sciences and Mathematics, California State University Fullerton; United States

Fil: Bonomo, Robert A. Departments of Medicine, Pharmacology, Molecular Biology and Microbiology, Biochemistry, Proteomics and Bioinformatics, School of Medicine, Case Western Reserve University; United States

Fil: Ramírez, Maria Soledad. Center for Applied Biotechnology Studies, Department of Biological Science, College of Natural Sciences and Mathematics, California State University Fullerton; United States
URI: http://sgc.anlis.gob.ar/handle/123456789/2511
ISSN: 2227-9059
DOI: 10.3390/biomedicines10030600
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