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dc.contributor.author Bahr, Guillermo
dc.contributor.author Vitor Horen, Luisina
dc.contributor.author Bethel, Christopher R.
dc.contributor.author Bonomo, Robert A.
dc.contributor.author Gonzalez, Lisandro Javier
dc.contributor.author Vila, Alejandro Jose
dc.date.available 2018-06-29T12:56:13Z
dc.date.issued 2018-01
dc.identifier.citation Bahr, Guillermo; Vitor Horen, Luisina; Bethel, Christopher R.; Bonomo, Robert A.; Gonzalez, Lisandro Javier; et al.; Clinical Evolution of New Delhi Metallo-β-Lactamase (NDM) optimizes resistance under Zn(II) Deprivation; American Society for Microbiology; Antimicrobial Agents and Chemotherapy; 62; 1; 1-2018; 1-32
dc.identifier.issn 0066-4804
dc.identifier.uri http://hdl.handle.net/11336/50572
dc.description.abstract Carbapenem-resistant Enterobacteriaceae (CRE) are rapidly spreading and taking a staggering toll on all health care systems, largely due to the dissemination of genes coding for potent carbapenemases. An important family of carbapenemases are the Zn(II)-dependent β-lactamases, known as metallo-β-lactamases (MBLs). Among them, the New Delhi metallo-β-lactamase (NDM) has experienced the fastest and widest geographical spread. While other clinically important MBLs are soluble periplasmic enzymes, NDMs are lipoproteins anchored to the outer membrane in Gram-negative bacteria. This unique cellular localization endows NDMs with enhanced stability upon the Zn(II) starvation elicited by the immune system response at the sites of infection. Since the first report of NDM-1, new allelic variants (16 in total) have been identified in clinical isolates differing by a limited number of substitutions. Here, we show that these variants have evolved by accumulating mutations that enhance their stability or the Zn(II) binding affinity in vivo, overriding the most common evolutionary pressure acting on catalytic efficiency. We identified the ubiquitous substitution M154L as responsible for improving the Zn(II) binding capabilities of the NDM variants. These results also reveal that Zn(II) deprivation imposes a strict constraint on the evolution of this MBL, overriding the most common pressures acting on catalytic performance, and shed light on possible inhibitory strategies.
dc.format application/pdf
dc.language.iso eng
dc.publisher American Society for Microbiology
dc.rights info:eu-repo/semantics/embargoedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject ANTIBIOTIC RESISTANCE
dc.subject CARBAPENEMASE
dc.subject METALLO-Β- LACTAMASE
dc.subject NDM
dc.subject NUTRITIONAL IMMUNITY
dc.subject ZN(II) LIMITATION
dc.subject.classification Otras Ciencias Biológicas
dc.subject.classification Ciencias Biológicas
dc.subject.classification CIENCIAS NATURALES Y EXACTAS
dc.title Clinical Evolution of New Delhi Metallo-β-Lactamase (NDM) optimizes resistance under Zn(II) Deprivation
dc.type info:eu-repo/semantics/article
dc.type info:ar-repo/semantics/artículo
dc.type info:eu-repo/semantics/publishedVersion
dc.date.updated 2018-06-28T14:13:44Z
dc.journal.volume 62
dc.journal.number 1
dc.journal.pagination 1-32
dc.journal.pais Estados Unidos
dc.description.fil Fil: Bahr, Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
dc.description.fil Fil: Vitor Horen, Luisina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
dc.description.fil Fil: Bethel, Christopher R.. Louis Stokes Cleveland VA Medical Center; Estados Unidos
dc.description.fil Fil: Bonomo, Robert A.. Louis Stokes Cleveland VA Medical Center; Estados Unidos
dc.description.fil Fil: Gonzalez, Lisandro Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
dc.description.fil Fil: Vila, Alejandro Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
dc.journal.title Antimicrobial Agents and Chemotherapy
dc.rights.embargoDate 2018-08-01
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1128/AAC.01849-17
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/url/http://aac.asm.org/content/62/1/e01849-17
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info:eu-repo/semantics/embargoedAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)