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The Use of a β-lactamase-based Conductimetric Biosensor Assay to Detect Biomolecular Interactions
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The Use of a β-lactamase-based Conductimetric Biosensor Assay to Detect Biomolecular Interactions

Published on: February 1, 2018

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

Carolina López1, Juan A Ayala2, Robert A Bonomo3,4,5

  • 1Instituto de Biología Molecular y Celular de Rosario (IBR, CONICET-UNR), S2000EZP, Rosario, Argentina.

Nature Communications
|August 11, 2019
PubMed

Insights

Metallo-β-lactamases (MBLs) spread is limited by their impact on bacterial fitness. Signal peptides determine MBL adaptability, explaining why some MBLs are restricted to specific bacterial hosts like Pseudomonas aeruginosa.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Public Health

Background:

  • Metallo-β-lactamases (MBLs) confer resistance to carbapenem antibiotics, posing a significant global health threat.
  • The spread of MBLs among Gram-negative pathogens is not fully explained by mobile genetic elements or resistance alone.

Purpose of the Study:

  • To investigate the factors determining the host range of metallo-β-lactamases (MBLs).
  • To understand the role of MBL expression in bacterial fitness and adaptability.

Main Methods:

  • Analysis of MBL signal peptide sequences and their impact on host adaptability.
  • Assessment of bacterial fitness and growth in the presence of MBL expression.
  • Investigating MBL processing and potential toxic intermediate accumulation in different bacterial hosts.

Main Results:

  • MBL host range is dictated by the fitness cost associated with their expression.
  • Inefficient MBL processing in uncommon hosts leads to toxic intermediates and reduced bacterial growth.
  • VIM-2 and SPM-1 are excluded from Escherichia coli and Acinetobacter baumannii due to fitness costs, but not from Pseudomonas aeruginosa.
  • NDM MBLs are expressed without fitness cost and secreted via outer membrane vesicles in various bacteria.

Conclusions:

  • Bacterial fitness, influenced by MBL signal peptide sequences, is a key determinant of MBL host range.
  • NDM MBLs exhibit broader adaptability due to a lack of associated fitness costs.
  • Protein determinants enabling host adaptability are crucial for the dissemination and adaptation of MBLs.

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