Protein determinants of dissemination and host specificity of metallo-β-lactamases

The worldwide dissemination of metallo-β-lactamases (MBLs), mediating resistance to carbapenem antibiotics, is a major public health problem. The extent of dissemination of MBLs such as VIM-2, SPM-1 and NDM among Gram-negative pathogens cannot be explained solely based on the associated mobile gen...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: López, Carolina, Ayala, Juan A., Bonomo, Robert A., González, Lisandro J., Vila, Alejandro J.
Formato: article artículo publishedVersion
Lenguaje:Inglés
Publicado: Nature 2021
Materias:
Metallo-beta-lactamases
Host Specificity
Dissemination
Carbapenems Resistance
Acceso en línea:http://hdl.handle.net/2133/19989
http://hdl.handle.net/2133/19989
Aporte de:
Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR) de Universidad Nacional de Rosario
id I15-R121-2133-19989
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 Metallo-beta-lactamases
Host Specificity
Dissemination
Carbapenems Resistance
spellingShingle Metallo-beta-lactamases
Host Specificity
Dissemination
Carbapenems Resistance
López, Carolina
Ayala, Juan A.
Bonomo, Robert A.
González, Lisandro J.
Vila, Alejandro J.
Protein determinants of dissemination and host specificity of metallo-β-lactamases
topic_facet Metallo-beta-lactamases
Host Specificity
Dissemination
Carbapenems Resistance
description The worldwide dissemination of metallo-β-lactamases (MBLs), mediating resistance to carbapenem antibiotics, is a major public health problem. The extent of dissemination of MBLs such as VIM-2, SPM-1 and NDM among Gram-negative pathogens cannot be explained solely based on the associated mobile genetic elements or the resistance phenotype. Here, we report that MBL host range is determined by the impact of MBL expression on bacterial fitness. The signal peptide sequence of MBLs dictates their adaptability to each host. In uncommon hosts, inefficient processing of MBLs leads to accumulation of toxic intermediates that compromises bacterial growth. This fitness cost explains the exclusion of VIM-2 and SPM-1 from Escherichia coli and Acinetobacter baumannii, and their confinement to Pseudomonas aeruginosa. By contrast, NDMs are expressed without any apparent fitness cost in different bacteria, and are secreted into outer membrane vesicles. We propose that the successful dissemination and adaptation of MBLs to different bacterial hosts depend on protein determinants that enable host adaptability and carbapenem resistance.
format article
artículo
publishedVersion
author López, Carolina
Ayala, Juan A.
Bonomo, Robert A.
González, Lisandro J.
Vila, Alejandro J.
author_facet López, Carolina
Ayala, Juan A.
Bonomo, Robert A.
González, Lisandro J.
Vila, Alejandro J.
author_sort López, Carolina
title Protein determinants of dissemination and host specificity of metallo-β-lactamases
title_short Protein determinants of dissemination and host specificity of metallo-β-lactamases
title_full Protein determinants of dissemination and host specificity of metallo-β-lactamases
title_fullStr Protein determinants of dissemination and host specificity of metallo-β-lactamases
title_full_unstemmed Protein determinants of dissemination and host specificity of metallo-β-lactamases
title_sort protein determinants of dissemination and host specificity of metallo-β-lactamases
publisher Nature
publishDate 2021
url http://hdl.handle.net/2133/19989
http://hdl.handle.net/2133/19989
work_keys_str_mv AT lopezcarolina proteindeterminantsofdisseminationandhostspecificityofmetalloblactamases
AT ayalajuana proteindeterminantsofdisseminationandhostspecificityofmetalloblactamases
AT bonomoroberta proteindeterminantsofdisseminationandhostspecificityofmetalloblactamases
AT gonzalezlisandroj proteindeterminantsofdisseminationandhostspecificityofmetalloblactamases
AT vilaalejandroj proteindeterminantsofdisseminationandhostspecificityofmetalloblactamases
AT lopezcarolina proteindeterminantsofdisseminationandhostspecificityofmetallobetalactamases
AT ayalajuana proteindeterminantsofdisseminationandhostspecificityofmetallobetalactamases
AT bonomoroberta proteindeterminantsofdisseminationandhostspecificityofmetallobetalactamases
AT gonzalezlisandroj proteindeterminantsofdisseminationandhostspecificityofmetallobetalactamases
AT vilaalejandroj proteindeterminantsofdisseminationandhostspecificityofmetallobetalactamases
bdutipo_str Repositorios
_version_ 1764820411229405185

Ejemplares similares