A novel fluorescent probe for the detection of AmpC beta-lactamase and the application in screening beta-lactamase inhibitors

Spectrochim Acta A Mol Biomol Spectrosc. 2020 Jun 15:234:118257. doi: 10.1016/j.saa.2020.118257. Epub 2020 Mar 14.

Abstract

The rapid detection of β-lactamases (Blas) and effective screening of Bla inhibitors are critically important and urgent for solving antibiotic resistance and improving precision medicine. Here a novel fluorescent probe CDC-559 was designed and synthesized, which can be used for the selective and direct detection of AmpC Blas. More importantly, it can realize screening the Bla inhibitors with sulbactam sodium and tazobactam as model compounds, and the half-maximal inhibitory concentration are 0.279 μM and 0.053 μM, respectively. CDC-559 can be applied not only to examine the resistance of bacterial strains, but also to categorize its mode of action specifically, which is consistent with the essential result of the Blas. The research suggests that CDC-559 probe has tremendous potential in the rapid detection of AmpC Blas as well as the strains with AmpC-encoded gene, which is instructive in promoting better antibiotic stewardship practices and developments.

Keywords: AmpC; Fluorescence probe; Inhibitor screening; β-Lactamase.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Bacteria / drug effects
  • Bacterial Proteins / metabolism*
  • Fluorescent Dyes / chemical synthesis
  • Fluorescent Dyes / chemistry*
  • Inhibitory Concentration 50
  • Kinetics
  • Limit of Detection
  • Microbial Sensitivity Tests
  • Phenotype
  • Spectrometry, Fluorescence
  • Spectrophotometry, Ultraviolet
  • beta-Lactamase Inhibitors / analysis*
  • beta-Lactamase Inhibitors / chemistry
  • beta-Lactamase Inhibitors / pharmacology*
  • beta-Lactamases / metabolism*

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Fluorescent Dyes
  • beta-Lactamase Inhibitors
  • AmpC beta-lactamases
  • beta-Lactamases