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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
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Carbapenemase
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Metallo-Β- Lactamase
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Ndm
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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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