Selective and Efficient Photoinactivation of Intracellular Staphylococcus aureus and MRSA with Little Accumulation of Drug Resistance: Application of a Ru(II) Complex with Photolabile Ligands

Novel antibacterial agents capable of efficiently sterilizing intracellular Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) but with low cytotoxicity and low resistance development are quite appealing. In this work, three Ru(II) complexes with photolabile ligands were explored to realize such a goal. Complex 3 (5 mu M) can inhibit more than 90% growth of S. aureus/MRSA that has invaded in J774A.1 cells upon visible light irradiation, being much more efficient than vancomycin. In similar conditions, negligible dark-and phototoxicity were found toward the host cells. The bactericidal activity is highly correlated with DNA covalent binding by the Ru(II) fractions generated after ligand photodissociation. Moreover, S. aureus quickly developed resistance toward vancomycin, while negligible resistance toward complex 3 even after 700 generations was obtained. These appealing results may pave a new way for fighting against intracellular antibiotic-resistant pathogens.

Automated summary

This research successfully developed a novel antibacterial agent capable of efficiently sterilizing intracellular methicillin-resistant Staphylococcus aureus using Ru(II) complexes with photolabile ligands, which have low cytotoxicity and resistance development. The bactericidal activity was highly correlated with DNA covalent binding by the Ru(II) fractions, and the complex showed negligible resistance development even after 700 generations, which could pave a new way for fighting against intracellular antibiotic-resistant pathogens.