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

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dc.citation.titleBiomedicineses
dc.citation.volume10
dc.creatorLe, Casin
dc.creatorPimentel, Camila
dc.creatorPasteran, Fernando
dc.creatorTuttobene, Marisel Romina
dc.creatorSubils, Tomás
dc.creatorEscalante, Jenny
dc.creatorNishimura, Brent
dc.creatorArriaga, Susana
dc.creatorCarranza, Aimee
dc.creatorMezcord, Vyanka
dc.creatorVila, Alejandro J.
dc.creatorCorso, Alejandra
dc.creatorActis, Luis A.
dc.creatorTolmasky, Marcelo E.
dc.creatorBonomo, Robert A.
dc.creatorRamírez, María Soledad
dc.date.accessioned2022-05-16T11:28:35Z
dc.date.available2022-05-16T11:28:35Z
dc.date.issued2022-03-03
dc.descriptionCefiderocol, 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.filFil: 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.filFil: 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.filFil: Pasteran, Fernando. National/Regional Reference Laboratory for Antimicrobial Resistance. Instituto Nacional de Enfermedades Infecciosas. Servicio Antimicrobianos; Argentina.es
dc.description.filFil: Tuttobene, Marisel Romina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Área Biología Molecular; Argentina.es
dc.description.filFil: Tuttobene, Marisel Romina. Instituto de Biología Molecular y Celular de Rosario (IBR); Argentina.es
dc.description.filFil: Subils, Tomás. Instituto de Procesos Biotecnológicos y Químicos de Rosario; Argentina.es
dc.description.filFil: 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.filFil: 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.filFil: 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.filFil: 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.filFil: 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.filFil: Vila, Alejandro J. Instituto de Biología Molecular y Celular de Rosario; Argentina.es
dc.description.filFil: Vila, Alejandro J. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Área Biofísica; Argentina.es
dc.description.filFil: Corso, Alejandra. National/Regional Reference Laboratory for Antimicrobial Resistance. Instituto Nacional de Enfermedades Infecciosas. Servicio Antimicrobianos; Argentina.es
dc.description.filFil: Actis, Luis A. Miami University. Department of Microbiology; United Kingdom.es
dc.description.filFil: 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.filFil: 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.filFil: Bonomo, Robert A. Research Service and GRECC. Louis Stokes Cleveland Department of Veterans Affairs Medical Center; United States.es
dc.description.filFil: Bonomo, Robert A. CWRU-Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology (Case VA CARES); United States.es
dc.description.filFil: 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.description.sponsorshipCleveland Department of Veterans Affairs: 1I01BX001974
dc.description.sponsorshipU.S. Department of Education HSI-STEM: P031C160152
dc.description.sponsorshipNational Institutes of Health (NIH): 2R15 AI047115, R01AI063517, R01AI072219, R01AI100560, SC3GM125556
dc.description.sponsorshipNational Institute on Minority Health and Health Disparities (NIMHD)
dc.description.sponsorshipBiomedical Laboratory Research and Development, VA Office of Research and Development (BLR&D, ORD)
dc.description.sponsorshipGeriatric Research Education and Clinical Center (GRECC): MHRT 2T37MD001368
dc.description.sponsorshipConsejo Nacional de Investigaciones Científicas y Técnicas (CONICET)
dc.formatapplication/pdf
dc.format.extent1-12es
dc.identifier.issn2227-9059es
dc.identifier.urihttp://hdl.handle.net/2133/23635
dc.language.isoenges
dc.publisherMDPIes
dc.relation.publisherversionhttps://www.mdpi.com/2227-9059/10/3/600
dc.relation.publisherversionhttps://doi.org/10.3390/biomedicines10030600
dc.rightsopenAccesses
dc.rights.holderLe, Casines
dc.rights.holderPimentel, Camilaes
dc.rights.holderPasteran, Fernandoes
dc.rights.holderTuttobene, Marisel Rominaes
dc.rights.holderSubils, Tomáses
dc.rights.holderEscalante, Jennyes
dc.rights.holderNishimura, Brentes
dc.rights.holderArriaga, Susanaes
dc.rights.holderCarranza, Aimeees
dc.rights.holderMezcord, Vyankaes
dc.rights.holderVila, Alejandro J.es
dc.rights.holderCorso, Alejandraes
dc.rights.holderActis, Luis A.es
dc.rights.holderTolmasky, Marcelo E.es
dc.rights.holderBonomo, Robert A.es
dc.rights.holderRamírez, María Soledades
dc.rights.textAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subjectAcinetobacter baumanniies
dc.subjectCefiderocoles
dc.subjectHuman fluidses
dc.subjectIrones
dc.subjectHuman serum albumines
dc.titleHuman Serum Proteins and Susceptibility of Acinetobacter baumannii to Cefiderocol: Role of Iron Transportes
dc.typepublishedVersion
dc.typearticle
dc.typeartículo
dc.type.collectionarticulo
dc.type.versionpublishedVersion

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