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

Author

Listed:
  • Carolina López

    (Instituto de Biología Molecular y Celular de Rosario (IBR, CONICET-UNR))

  • Juan A. Ayala

    (Centro de Biología Molecular Severo Ochoa, Agencia Estatal Consejo Superior de Investigaciones Científicas (CSIC-UAM), Campus de Cantoblanco)

  • Robert A. Bonomo

    (Medical Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center
    Case Western Reserve University School of Medicine
    CWRU-Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology (Case VA CARES))

  • Lisandro J. González

    (Instituto de Biología Molecular y Celular de Rosario (IBR, CONICET-UNR)
    Universidad Nacional de Rosario)

  • Alejandro J. Vila

    (Instituto de Biología Molecular y Celular de Rosario (IBR, CONICET-UNR)
    CWRU-Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology (Case VA CARES)
    Universidad Nacional de Rosario)

Abstract

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.

Suggested Citation

  • Carolina López & Juan A. Ayala & Robert A. Bonomo & Lisandro J. González & Alejandro J. Vila, 2019. "Protein determinants of dissemination and host specificity of metallo-β-lactamases," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11615-w
    DOI: 10.1038/s41467-019-11615-w
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    Cited by:

    1. Cristina Herencias & Laura Álvaro-Llorente & Paula Ramiro-Martínez & Ariadna Fernández-Calvet & Ada Muñoz-Cazalla & Javier DelaFuente & Fabrice E. Graf & Laura Jaraba-Soto & Juan Antonio Castillo-Polo, 2024. "β-lactamase expression induces collateral sensitivity in Escherichia coli," Nature Communications, Nature, vol. 15(1), pages 1-11, December.

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