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

Metallo-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 activit...

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Autores principales: Bahr, Guillermo, González, Lisandro J., Vila, Alejandro J.
Formato: article artículo publishedVersion
Lenguaje:Inglés
Publicado: Elsevier 2022
Materias:
Zinc
Metallo-b-lactamases
Antibiotic resistance
Protein evolution
Periplasmic zinc homeostasis
Acceso en línea:http://hdl.handle.net/2133/23389
http://hdl.handle.net/2133/23389
Aporte de:
Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR) de Universidad Nacional de Rosario
id I15-R121-2133-23389
record_format dspace
institution Universidad Nacional de Rosario
institution_str I-15
repository_str R-121
collection Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR)
language Inglés
orig_language_str_mv eng
topic Zinc
Metallo-b-lactamases
Antibiotic resistance
Protein evolution
Periplasmic zinc homeostasis
spellingShingle Zinc
Metallo-b-lactamases
Antibiotic resistance
Protein evolution
Periplasmic zinc homeostasis
Bahr, Guillermo
González, Lisandro J.
Vila, Alejandro J.
Metallo-β-lactamases and a tug-of-war for the available zinc at the host–pathogen interface
topic_facet Zinc
Metallo-b-lactamases
Antibiotic resistance
Protein evolution
Periplasmic zinc homeostasis
description Metallo-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.
format article
artículo
publishedVersion
author Bahr, Guillermo
González, Lisandro J.
Vila, Alejandro J.
author_facet Bahr, Guillermo
González, Lisandro J.
Vila, Alejandro J.
author_sort Bahr, Guillermo
title Metallo-β-lactamases and a tug-of-war for the available zinc at the host–pathogen interface
title_short Metallo-β-lactamases and a tug-of-war for the available zinc at the host–pathogen interface
title_full Metallo-β-lactamases and a tug-of-war for the available zinc at the host–pathogen interface
title_fullStr Metallo-β-lactamases and a tug-of-war for the available zinc at the host–pathogen interface
title_full_unstemmed Metallo-β-lactamases and a tug-of-war for the available zinc at the host–pathogen interface
title_sort metallo-β-lactamases and a tug-of-war for the available zinc at the host–pathogen interface
publisher Elsevier
publishDate 2022
url http://hdl.handle.net/2133/23389
http://hdl.handle.net/2133/23389
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AT gonzalezlisandroj metalloblactamasesandatugofwarfortheavailablezincatthehostpathogeninterface
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bdutipo_str Repositorios
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