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

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dc.creator Le, Casin
dc.creator Pimentel, Camila
dc.creator Pasteran, Fernando
dc.creator Tuttobene, Marisel Romina
dc.creator Subils, Tomás
dc.creator Escalante, Jenny
dc.creator Nishimura, Brent
dc.creator Arriaga, Susana
dc.creator Carranza, Aimee
dc.creator Mezcord, Vyanka
dc.creator Vila, Alejandro J.
dc.creator Corso, Alejandra
dc.creator Actis, Luis A.
dc.creator Tolmasky, Marcelo E.
dc.creator Bonomo, Robert A.
dc.creator Ramírez, María Soledad
dc.date.accessioned 2022-05-16T11:28:35Z
dc.date.available 2022-05-16T11:28:35Z
dc.date.issued 2022-03-03
dc.identifier.issn 2227-9059 es
dc.identifier.uri http://hdl.handle.net/2133/23635
dc.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. es
dc.description.sponsorship Cleveland Department of Veterans Affairs: 1I01BX001974
dc.description.sponsorship U.S. Department of Education HSI-STEM: P031C160152
dc.description.sponsorship National Institutes of Health (NIH): 2R15 AI047115, R01AI063517, R01AI072219, R01AI100560, SC3GM125556
dc.description.sponsorship National Institute on Minority Health and Health Disparities (NIMHD)
dc.description.sponsorship Biomedical Laboratory Research and Development, VA Office of Research and Development (BLR&D, ORD)
dc.description.sponsorship Geriatric Research Education and Clinical Center (GRECC): MHRT 2T37MD001368
dc.description.sponsorship Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)
dc.format application/pdf
dc.format.extent 1-12 es
dc.language.iso eng es
dc.publisher MDPI es
dc.rights openAccess es
dc.rights.uri https://creativecommons.org/licenses/by/4.0/ *
dc.subject Acinetobacter baumannii es
dc.subject Cefiderocol es
dc.subject Human fluids es
dc.subject Iron es
dc.subject Human serum albumin es
dc.title Human Serum Proteins and Susceptibility of Acinetobacter baumannii to Cefiderocol: Role of Iron Transport es
dc.type article
dc.type artículo
dc.type publishedVersion
dc.rights.holder Le, Casin es
dc.rights.holder Pimentel, Camila es
dc.rights.holder Pasteran, Fernando es
dc.rights.holder Tuttobene, Marisel Romina es
dc.rights.holder Subils, Tomás es
dc.rights.holder Escalante, Jenny es
dc.rights.holder Nishimura, Brent es
dc.rights.holder Arriaga, Susana es
dc.rights.holder Carranza, Aimee es
dc.rights.holder Mezcord, Vyanka es
dc.rights.holder Vila, Alejandro J. es
dc.rights.holder Corso, Alejandra es
dc.rights.holder Actis, Luis A. es
dc.rights.holder Tolmasky, Marcelo E. es
dc.rights.holder Bonomo, Robert A. es
dc.rights.holder Ramírez, María Soledad es
dc.relation.publisherversion https://www.mdpi.com/2227-9059/10/3/600
dc.relation.publisherversion https://doi.org/10.3390/biomedicines10030600
dc.rights.text Attribution 4.0 International (CC BY 4.0)
dc.citation.title Biomedicines es
dc.description.fil Fil: Le, Casin. California State University Fullerton. College of Natural Sciences and Mathematics. Department of Biological Science. Center for Applied Biotechnology Studies; United States. es
dc.description.fil Fil: Pimentel, Camila. California State University Fullerton. College of Natural Sciences and Mathematics. Department of Biological Science. Center for Applied Biotechnology Studies; United States. es
dc.description.fil Fil: Pasteran, Fernando. National/Regional Reference Laboratory for Antimicrobial Resistance. Instituto Nacional de Enfermedades Infecciosas. Servicio Antimicrobianos; Argentina. es
dc.description.fil Fil: Tuttobene, Marisel Romina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Área Biología Molecular; Argentina. es
dc.description.fil Fil: Tuttobene, Marisel Romina. Instituto de Biología Molecular y Celular de Rosario (IBR); Argentina. es
dc.description.fil Fil: Subils, Tomás. Instituto de Procesos Biotecnológicos y Químicos de Rosario; Argentina. es
dc.description.fil Fil: Escalante, Jenny. California State University Fullerton. College of Natural Sciences and Mathematics. Department of Biological Science. Center for Applied Biotechnology Studies; United States. es
dc.description.fil Fil: Nishimura, Brent. California State University Fullerton. College of Natural Sciences and Mathematics. Department of Biological Science. Center for Applied Biotechnology Studies; United States. es
dc.description.fil Fil: Arriaga, Susana. California State University Fullerton. College of Natural Sciences and Mathematics. Department of Biological Science. Center for Applied Biotechnology Studies; United States. es
dc.description.fil Fil: Carranza, Aimee. California State University Fullerton. College of Natural Sciences and Mathematics. Department of Biological Science. Center for Applied Biotechnology Studies; United States. es
dc.description.fil Fil: Mezcord, Vyanka. California State University Fullerton. College of Natural Sciences and Mathematics. Department of Biological Science. Center for Applied Biotechnology Studies; United States. es
dc.description.fil Fil: Vila, Alejandro J. Instituto de Biología Molecular y Celular de Rosario; Argentina. es
dc.description.fil Fil: Vila, Alejandro J. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Área Biofísica; Argentina. es
dc.description.fil Fil: Corso, Alejandra. National/Regional Reference Laboratory for Antimicrobial Resistance. Instituto Nacional de Enfermedades Infecciosas. Servicio Antimicrobianos; Argentina. es
dc.description.fil Fil: Actis, Luis A. Miami University. Department of Microbiology; United Kingdom. es
dc.description.fil Fil: Tolmasky, Marcelo E. California State University Fullerton. College of Natural Sciences and Mathematics. Department of Biological Science. Center for Applied Biotechnology Studies; United States. es
dc.description.fil Fil: Bonomo, Robert A. Case Western Reserve University. School of Medicine. Departments of Medicine, Pharmacology, Molecular Biology and Microbiology, Biochemistry, Proteomics and Bioinformatics; United States. es
dc.description.fil Fil: Bonomo, Robert A. Research Service and GRECC. Louis Stokes Cleveland Department of Veterans Affairs Medical Center; United States. es
dc.description.fil Fil: Bonomo, Robert A. CWRU-Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology (Case VA CARES); United States. es
dc.description.fil Fil: Ramírez, María Soledad. California State University Fullerton. College of Natural Sciences and Mathematics. Department of Biological Science. Center for Applied Biotechnology Studies; United States. es
dc.type.collection articulo
dc.type.version publishedVersion es


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