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

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dc.citation.titleNature Communicationses
dc.citation.volume10es
dc.creatorLópez, Carolina
dc.creatorAyala, Juan A.
dc.creatorBonomo, Robert A.
dc.creatorGonzález, Lisandro J.
dc.creatorVila, Alejandro J.
dc.date.accessioned2021-03-03T18:27:01Z
dc.date.available2021-03-03T18:27:01Z
dc.date.issued2019-08-09
dc.descriptionThe 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.es
dc.description.filFil: López, Carolina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR -CONICET); Argentina.es
dc.description.filFil: Ayala, Juan A. Consejo Superior de Investigaciones Científicas (CSIC) - Universidad Autónoma de Madrid (UAM). Centro de Biología Molecular Severo Ochoa (CBMSO); España.es
dc.description.filFil: Bonomo, Robert A. Louis Stokes Cleveland Department of Veterans Affairs Medical Center. Medical Service; United States.es
dc.description.filFil: Bonomo, Robert A. Case Western Reserve University (CWRU). School of Medicine. Departments of Medicine, Pharmacology, Molecular Biology and Microbiology, Biochemistry, Proteomics and Bioinformatics; United States.es
dc.description.filFil: Bonomo, Robert A. Case Western Reserve University CWRU - Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology. Case VA CARES; United States.es
dc.description.filFil: González, Lisandro J. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR -CONICET); Argentina.es
dc.description.filFil: González, Lisandro J. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Área Biofísica; Argentina.es
dc.description.filFil: Vila, Alejandro J. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR -CONICET); Argentina.es
dc.description.filFil: Vila, Alejandro J. Case Western Reserve University CWRU - Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology. Case VA CARES; United States.es
dc.description.filFil: Vila, Alejandro J. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Área Biofísica; Argentina.es
dc.description.sponsorshipNational Institutes of Health (NIH): R01AI100560, R01AI063517 and R01AI072219es
dc.description.sponsorshipAgencia Nacional de Promoción Científica y Tecnológica (ANPCyT)es
dc.description.sponsorshipCleveland Department of Veterans Affairs: Award Number 1I01BX001974es
dc.description.sponsorshipEuropean Commission: DIVINOCELL FP7 HEALTH-F3-2009-223431es
dc.description.sponsorshipMinisterio de Ciencia e Innovación (MICINN) de España: BFU2009-09200 y IPT2011-0964-900000es
dc.formatapplication/pdf
dc.format.extent1-11es
dc.identifier.issn2041-1723es
dc.identifier.urihttp://hdl.handle.net/2133/19989
dc.language.isoenges
dc.publisherNaturees
dc.relation.publisherversionhttps://doi.org/10.1038/s41467-019-11615-wes
dc.relation.publisherversionhttps://www.nature.com/articles/s41467-019-11615-wes
dc.rightsopenAccesses
dc.rights.holderUniversidad Nacional de Rosarioes
dc.rights.holderLópez, Carolinaes
dc.rights.holderAyala, Juan A.es
dc.rights.holderBonomo, Robert A.es
dc.rights.holderGonzález, Lisandro J.es
dc.rights.holderVila, Alejandro J.es
dc.rights.textAttribution 4.0 International (CC BY 4.0)es
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subjectMetallo-beta-lactamaseses
dc.subjectHost Specificityes
dc.subjectDisseminationes
dc.subjectCarbapenems Resistancees
dc.titleProtein determinants of dissemination and host specificity of metallo-β-lactamaseses
dc.titleProtein determinants of dissemination and host specificity of metallo-beta-lactamaseses
dc.typearticle
dc.typeartículo
dc.typepublishedVersion
dc.type.collectionarticulo
dc.type.versionpublishedVersiones

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