Related Experiment Video

Updated: Aug 6, 2026

The Use of a β-lactamase-based Conductimetric Biosensor Assay to Detect Biomolecular Interactions
08:06

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

Published on: February 1, 2018

PER-14, a β-lactamase variant with reduced sensitivity to avibactam and relebactam

Melina Ruggiero1,2, Melina García Alonso1, Salvador I Drusin3,4

  • 1Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Instituto de Investigaciones en Bacteriología y Virología Molecular (IBaViM), Buenos Aires, Argentina.

Antimicrobial Agents and Chemotherapy
|July 21, 2026
PubMed

Insights

New PER-14 enzymes in bacteria like Pseudomonas and Acinetobacter resist common antibiotics, including cefiderocol. This resistance stems from a specific S130T substitution, impacting drug binding and treatment options.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Drug Discovery

Background:

  • PER-1 and PER-2 enzymes confer resistance to critical antibiotics in Gram-negative bacteria.
  • Increasing antibiotic resistance necessitates understanding novel resistance mechanisms.

Purpose of the Study:

  • To characterize the novel PER-14 beta-lactamase and its resistance profile.
  • To elucidate the structural basis for PER-14's resistance to avibactam and relebactam.

Main Methods:

  • Functional enzyme assays to determine hydrolysis profiles.
  • In silico modeling to analyze inhibitor binding.
  • Site-directed mutagenesis to confirm the role of the S130T substitution.

Main Results:

  • PER-14 exhibits resistance to avibactam and relebactam.
  • The S130T substitution is crucial for PER-14's resistance to these inhibitors.
  • PER-14 retains extended-spectrum activity and hydrolyzes cefiderocol.

Conclusions:

  • PER-14 represents a significant challenge in treating infections caused by resistant bacteria.
  • The S130T substitution alters the binding of beta-lactamase-directed inhibitors.
  • Further research is needed to develop new therapeutic strategies against PER-14-producing bacteria.
Keywords:
ESBLPararheinheimeraaztreonam/relebactamceftazidimaseceftazidime/avibactamdiazabicyclooctane

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