Deciphering the evolution of metallo-β-lactamases: A journey from the test tube to the bacterial periplasm

Understanding the evolution of metallo-β-lactamases (MBLs) is fundamental to deciphering the mechanistic basis of resistance to carbapenems in pathogenic and opportunistic bacteria. Presently, these MBL-producing pathogens are linked to high rates of morbidity and mortality worldwide. However, the s...

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Autores principales: López, Carolina, Delmonti, Juliana, Bonomo, Robert A., Vila, Alejandro J.
Formato: article artículo publishedVersion
Lenguaje:Inglés
Publicado: American Society for Biochemistry and Molecular Biology Inc. 2022
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Acceso en línea:http://hdl.handle.net/2133/23340
http://hdl.handle.net/2133/23340
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id I15-R121-2133-23340
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 Antibiotic resistance
Metallo-β-lactamase
Protein evolution
Periplasmic space
Outer membrane vesicles
Zn(II) limitation
spellingShingle Antibiotic resistance
Metallo-β-lactamase
Protein evolution
Periplasmic space
Outer membrane vesicles
Zn(II) limitation
López, Carolina
Delmonti, Juliana
Bonomo, Robert A.
Vila, Alejandro J.
Deciphering the evolution of metallo-β-lactamases: A journey from the test tube to the bacterial periplasm
topic_facet Antibiotic resistance
Metallo-β-lactamase
Protein evolution
Periplasmic space
Outer membrane vesicles
Zn(II) limitation
description Understanding the evolution of metallo-β-lactamases (MBLs) is fundamental to deciphering the mechanistic basis of resistance to carbapenems in pathogenic and opportunistic bacteria. Presently, these MBL-producing pathogens are linked to high rates of morbidity and mortality worldwide. However, the study of the biochemical and biophysical features of MBLs in vitro provides an incomplete picture of their evolutionary potential, since this limited and artificial environment disregards the physiological context where evolution and selection take place. Herein, we describe recent efforts aimed to address the evolutionary traits acquired by different clinical variants of MBLs in conditions mimicking their native environment (the bacterial periplasm) and considering whether they are soluble or membrane-bound proteins. This includes addressing the metal content of MBLs within the cell under zinc starvation conditions and the context provided by different bacterial hosts that result in particular resistance phenotypes. Our analysis highlights recent progress bridging the gap between in vitro and in-cell studies.
format article
artículo
publishedVersion
author López, Carolina
Delmonti, Juliana
Bonomo, Robert A.
Vila, Alejandro J.
author_facet López, Carolina
Delmonti, Juliana
Bonomo, Robert A.
Vila, Alejandro J.
author_sort López, Carolina
title Deciphering the evolution of metallo-β-lactamases: A journey from the test tube to the bacterial periplasm
title_short Deciphering the evolution of metallo-β-lactamases: A journey from the test tube to the bacterial periplasm
title_full Deciphering the evolution of metallo-β-lactamases: A journey from the test tube to the bacterial periplasm
title_fullStr Deciphering the evolution of metallo-β-lactamases: A journey from the test tube to the bacterial periplasm
title_full_unstemmed Deciphering the evolution of metallo-β-lactamases: A journey from the test tube to the bacterial periplasm
title_sort deciphering the evolution of metallo-β-lactamases: a journey from the test tube to the bacterial periplasm
publisher American Society for Biochemistry and Molecular Biology Inc.
publishDate 2022
url http://hdl.handle.net/2133/23340
http://hdl.handle.net/2133/23340
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