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Updated: Jan 10, 2026

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Are Putative Beta-Lactamases Posing a Potential Future Threat?

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This study identifies potential beta-lactamase threats by analyzing enzyme candidates from diverse sources. A new framework prioritizes enzymes based on genetic features, aiding global antimicrobial resistance surveillance.

Keywords:
antimicrobial resistancebeta-lactamaseshorizontal gene transferpublic health

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Area of Science:

  • Genomics and Bioinformatics
  • Microbiology
  • Public Health

Background:

  • Antimicrobial resistance (AMR) is a significant global health challenge, with beta-lactamase enzymes conferring resistance to crucial beta-lactam antibiotics.
  • A prior survey identified 2340 potential beta-lactamases, prompting a focused analysis of 129 prioritized candidates.

Purpose of the Study:

  • To develop and validate a framework for early detection and prioritization of novel beta-lactamase candidates.
  • To assess the potential for horizontal gene transfer and mobility of these resistance genes across different bacterial reservoirs.

Main Methods:

  • Analysis of 129 prioritized beta-lactamase candidates from environmental, animal, and human sources.
  • Motif-centric assessment of catalytic residues and evaluation of genomic context using the Index of Proximal Mobility (IPM).
  • Phylogenetic analysis and AI-based substrate predictions for exploratory insights.

Main Results:

  • Candidates represented all Ambler classes (A-D) with conserved catalytic motifs, suggesting potential activity.
  • Nine percent of candidate loci showed high IPM, indicating genomic contexts conducive to horizontal gene transfer, often near mobile elements.
  • Identical Class A enzymes were found across multiple genera and continents, frequently associated with mobilization proteins.

Conclusions:

  • A reproducible, bias-aware framework for prioritizing beta-lactamase candidates based on motif integrity and mobility context is proposed.
  • This framework supports global surveillance initiatives (GLASS/EARS-Net) and integrates a One Health approach.
  • Experimental validation is crucial to confirm the function, mobility, and clinical relevance of prioritized candidates.