Exploiting a bacterial drug-resistance mechanism: a light-activated construct for the destruction of MRSA

Angew Chem Int Ed Engl. 2009;48(12):2148-51. doi: 10.1002/anie.200804804.

Abstract

A cunning and dangerous plan foiled! An enzyme-specific molecular construct exploits the overexpression of beta-lactamase in several drug-resistant bacteria. Specific photodynamic toxicity was detected towards beta-lactam-resistant methicillin-resistant Staphylococcus aureus (MRSA), whereby the usual mechanism for antibiotic resistance (cleavage of the beta-lactam ring) releases the phototoxic component from the prodrug (see picture; Q = quencher).

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Kinetics
  • Methicillin-Resistant Staphylococcus aureus / metabolism
  • Methicillin-Resistant Staphylococcus aureus / radiation effects*
  • Microbial Sensitivity Tests
  • Photochemotherapy
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology
  • Prodrugs / chemistry
  • Prodrugs / pharmacology
  • beta-Lactamases / metabolism
  • beta-Lactamases / radiation effects*
  • beta-Lactamases / toxicity

Substances

  • Photosensitizing Agents
  • Prodrugs
  • beta-Lactamases