Peptide-Ruthenium Conjugate as an Efficient Photosensitizer for the Inactivation of Multidrug-Resistant Bacteria.
Scott PierceMurphy P JenningsSamuel A JulianoAlfredo M Angeles-BozaPublished in: Inorganic chemistry (2020)
Antimicrobial photodynamic therapy (APDT) has gained increased attention because of its broad spectrum activity and lower likelihood to elicit bacterial resistance. Although many photosensitizers excel at eradicating Gram-positive bacterial infections, they are generally less potent when utilized against Gram-negative bacteria. We hypothesized that conjugating the DNA-targeting, antimicrobial peptide buforin II to a metal-based photosensitizer would result in a potent APDT agent. Herein, we present the synthesis and characterization of a buforin II-[Ru(bpy)3]2+ bioconjugate (1). The submicromolar activity of 1 against the multidrug-resistant strains Escherichia coli AR 0114 and Acinetobacter baumannii Naval-17 indicates strong synergy between the ruthenium complex and buforin II. Our mechanistic studies point to an increased rate of DNA damage by 1 compared to [Ru(bpy)3]2+. These results suggest that conjugating metal complexes to antimicrobial peptides can lead to potent antimicrobial agents.
Keyphrases
- photodynamic therapy
- multidrug resistant
- acinetobacter baumannii
- gram negative
- drug resistant
- escherichia coli
- klebsiella pneumoniae
- dna damage
- fluorescence imaging
- staphylococcus aureus
- anti inflammatory
- pseudomonas aeruginosa
- cancer therapy
- oxidative stress
- single molecule
- cystic fibrosis
- circulating tumor
- energy transfer
- cell free
- biofilm formation