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Acinetobacter baumannii response to cefiderocol challenge in human urine

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dc.citation.titleScientific Reports
dc.citation.volume12
dc.creatorNishimura, Brent
dc.creatorEscalante, Jenny
dc.creatorTuttobene, Marisel Romina
dc.creatorSubils, Tomás
dc.creatorMezcord, Vyanka
dc.creatorPimentel, Camila
dc.creatorGeorgeos, Nardin
dc.creatorPasteran, Fernando
dc.creatorRodríguez, Cecilia
dc.creatorSieira, Rodrigo
dc.creatorActis, Luis A.
dc.creatorTolmasky,, Marcelo E.
dc.creatorBonomo, Robert A.
dc.creatorRamírez, María Soledad
dc.date.accessioned2024-04-16T19:58:57Z
dc.date.available2024-04-16T19:58:57Z
dc.date.issued2022-05-24
dc.description.abstractCefiderocol (CFDC) is a novel chlorocatechol-substituted siderophore antibiotic approved to treat complicated urinary tract infections (cUTI) and hospital-acquired and ventilator-acquired pneumonia (HAP/VAP). Previous work determined that albumin-rich human fluids increase the minimum inhibitory concentration (MICs) of Acinetobacter baumannii against CFDC and reduce the expression of genes related to iron uptake systems. This latter effect may contribute to the need for higher concentrations of CFDC to inhibit growth. The presence of human urine (HU), which contains low albumin concentrations, did not modify MIC values of two carbapenem-resistant A. baumannii. Levels of resistance to CFDC were not modified by HU in strain AMA40 but were reduced in strain AB5075. Expanding the studies to other carbapenem-resistant A. baumannii isolates showed that the presence of HU resulted in unmodified or reduced MIC of CDFC values. The expression of piuA, pirA, bauA, and bfnH determined by qRT-PCR was enhanced in A. baumannii AMA40 and AB5075 by the presence of HU in the culture medium. All four tested genes code for functions related to recognition and transport of ferric-siderophore complexes. The effect of HU on expression of pbp1, pbp3, blaOXA-51-like, blaADC, and blaNDM-1, genes associated with resistance to β-lactams, as well as genes coding for efflux pumps and porins was variable, showing dependence with the strain analyzed. We conclude that the lack of significant concentrations of albumin and free iron in HU makes this fluid behave differently from others we tested. Unlike other albumin rich fluids, the presence of HU does not impact the antibacterial activity of CFDC when tested against A. baumannii.
dc.description.filFil: Nishimura, Brent. California State University Fullerton. College of Natural Sciences and Mathematics. Center for Applied Biotechnology Studies. Department of Biological Science. Center for Applied Biotechnology Studies; United States.
dc.description.filFil: Escalante, Jenny. California State University Fullerton. College of Natural Sciences and Mathematics. Center for Applied Biotechnology Studies. Department of Biological Science. Center for Applied Biotechnology Studies; United States.
dc.description.filFil: Mezcord, Vyanka. California State University Fullerton. College of Natural Sciences and Mathematics. Center for Applied Biotechnology Studies. Department of Biological Science. Center for Applied Biotechnology Studies; United States.
dc.description.filFil: Pimentel, Camila. California State University Fullerton. College of Natural Sciences and Mathematics. Center for Applied Biotechnology Studies. Department of Biological Science. Center for Applied Biotechnology Studies; United States.
dc.description.filFil: Georgeos, Nardin. California State University Fullerton. College of Natural Sciences and Mathematics. Center for Applied Biotechnology Studies. Department of Biological Science. Center for Applied Biotechnology Studies; United States.
dc.description.filFil: Tolmasky, Marcelo E. California State University Fullerton. College of Natural Sciences and Mathematics. Center for Applied Biotechnology Studies. Department of Biological Science; United States.
dc.description.filFil: Ramírez, María Soledad. California State University Fullerton. College of Natural Sciences and Mathematics. Center for Applied Biotechnology Studies. Department of Biological Science. Center for Applied Biotechnology Studies; United States.
dc.description.filFil: Tuttobene, Marisel Romina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Área Biología Molecular; Argentina.
dc.description.filFil: Tuttobene, Marisel Romina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.
dc.description.filFil: Subils, Tomás. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Procesos Biotecnológicos y Químicos de Rosario (IPROBYQ-CONICET); Argentina.
dc.description.filFil: Pasteran, Fernando. ANLIS "Dr. Carlos G. Malbrán". Instituto Nacional de Enfermedades Infecciosas. Servicio Antimicrobianos. National Regional Reference Laboratory for Antimicrobial Resistance (NRL); Argentina.
dc.description.filFil: Rodríguez, Cecilia. Centro de Referencia Para Lactobacilos (CERELA-CONICET); Argentina.
dc.description.filFil: Sieira, Rodrigo. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir (FIL-IIBBA-CONICET); Argentina.
dc.description.filFil: Actis, Luis A. Miami University. Department of Microbiology; United States.
dc.description.filFil: Bonomo, Robert A. Louis Stokes Cleveland Department of Veterans Affairs Medical Center. Research Service and GRECC; United States.
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.
dc.description.filFil: Bonomo, Robert A. CWRU-Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology; United States.
dc.description.sponsorshipNational Institutes of Health (NIH): SC3GM125556, R01AI100560, R01AI063517, R01AI072219, 2R15 AI047115
dc.description.sponsorshipCleveland Department of Veterans Affairs
dc.description.sponsorshipBiomedical Laboratory Research & Development Service of the VA Office of Research and Development: award number 1I01BX001974
dc.description.sponsorshipDevelopment and the Geriatric Research Education and Clinical Center VISN 10
dc.description.sponsorshipNational Institute on Minority Health and Health Disparities, National Institute of Health: grant MHRT 2T37MD001368
dc.description.sponsorshipProject RAISE, U.S. Department of Education HSI-STEM: award number P031C160152
dc.description.sponsorshipConsejo Nacional de Investigaciones Científicas y Técnicas (CONICET)
dc.description.versionpeerreviewed
dc.format.extent1-9
dc.identifier.issn2045-2322
dc.identifier.urihttps://hdl.handle.net/2133/26896
dc.language.isoen
dc.publisherSpringer Nature
dc.relation.publisherversionhttps://doi.org/10.1038/s41598-022-12829-7
dc.relation.publisherversionhttps://www.nature.com/articles/s41598-022-12829-7
dc.rightsopenAccess
dc.rights.holderNishimura, Brent
dc.rights.holderEscalante, Jenny
dc.rights.holderTuttobene, Marisel Romina
dc.rights.holderSubils, Tomás
dc.rights.holderMezcord, Vyanka
dc.rights.holderPimentel, Camila
dc.rights.holderGeorgeos, Nardin
dc.rights.holderPasteran, Fernando
dc.rights.holderRodríguez, María Cecilia
dc.rights.holderSieira, Rodrigo
dc.rights.holderActis, Luis A.
dc.rights.holderTolmasky, Marcelo E.
dc.rights.holderBonomo, Robert A.
dc.rights.holderRamírez, María Soledad
dc.rights.holderUniversidad Nacional de Rosario
dc.rights.textAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAcinetobacter baumannii
dc.subjectHuman urine
dc.subjectCefiderocol
dc.subjectIron
dc.subjectHuman serum albumin
dc.subjectCarbapenem resistance
dc.titleAcinetobacter baumannii response to cefiderocol challenge in human urine
dc.typearticulo
dc.type.collectionarticulo
dc.type.versionpublishedVersion

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