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Metallo-β-lactamases and a tug-of-war for the available zinc at the host–pathogen interface

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dc.citation.titleCurrent Opinion in Chemical Biologyes
dc.citation.volume66
dc.creatorBahr, Guillermo
dc.creatorGonzález, Lisandro Javier
dc.creatorVila, Alejandro J.
dc.date.accessioned2022-04-11T14:44:52Z
dc.date.available2022-04-11T14:44:52Z
dc.date.issued2022
dc.descriptionMetallo-b-lactamases (MBLs) are zinc-dependent hydrolases that inactivate virtually all b-lactam antibiotics. The expression of MBLs by Gram-negative bacteria severely limits the therapeutic options to treat infections. MBLs bind the essential metal ions in the bacterial periplasm, and their activity is challenged upon the zinc starvation conditions elicited by the native immune response. Metal depletion compromises both the enzyme activity and stability in the periplasm, impacting on the resistance profile in vivo. Thus, novel inhibitory approaches involve the use of chelating, agents or metal-based drugs that displace the native metal ion. However, newer MBL variants incorporate mutations that improve their metal binding abilities or stabilize the metal-depleted form, revealing that metal starvation is a driving force acting on MBL evolution. Future challenges require addressing the gap between in cell and in vitro studies, dissecting the mechanism for MBL metalation and determining the metal content in situ.es
dc.description.filFil: Bahr, Guillermo. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.es
dc.description.filFil: Bahr, Guillermo. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Área Biofísica; Argentina.es
dc.description.filFil: González, Lisandro Javier. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.es
dc.description.filFil: González, Lisandro Javier. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Área Biofísica; Argentina.es
dc.description.filFil: Vila, Alejandro J. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.es
dc.description.filFil: Vila, Alejandro J. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Área Biofísica; Argentina.es
dc.description.sponsorshipNational Institute of Allergy and Infectious Diseases (NIAID): 2R01AI100560-06A1
dc.description.sponsorshipConsejo Nacional de Investigaciones Científicas y Técnicas (CONICET)
dc.description.sponsorshipAgencia Nacional de Promoción Científica y Tecnológica (ANPCyT): PICT-2016-1657
dc.description.sponsorshipUniversidad del Rosario
dc.formatapplication/pdf
dc.format.extent1-9es
dc.identifier.issn1367-5931es
dc.identifier.urihttp://hdl.handle.net/2133/23389
dc.language.isoenges
dc.publisherElsevieres
dc.relation.publisherversionhttps://doi.org/10.1016/j.cbpa.2021.102103
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/pii/S1367593121001423
dc.rightsopenAccesses
dc.rights.holderElsevieres
dc.rights.textAttribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)es
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectZinces
dc.subjectMetallo-β-lactamaseses
dc.subjectAntibiotic resistancees
dc.subjectProtein evolutiones
dc.subjectPeriplasmic zinc homeostasises
dc.titleMetallo-β-lactamases and a tug-of-war for the available zinc at the host–pathogen interfacees
dc.typepublishedVersion
dc.typearticle
dc.typeartículo
dc.type.collectionarticulo
dc.type.versionpublishedVersion

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