Mitochondria-Targeted Curcumin: A Potent Antibacterial Agent against Methicillin-Resistant Staphylococcus aureus with a Possible Intracellular ROS Accumulation as the Mechanism of Action.

Autor:	Leferman CE; Department of Pharmacology, Medical Specialties II, 'Grigore T. Popa' University of Medicine and Pharmacy, 700115 Iasi, Romania.; Department of Ophthalmology, 'Grigore T. Popa' University of Medicine and Pharmacy, 700115 Iasi, Romania., Stoica L; Department of Cell and Molecular Biology, 'Grigore T. Popa' University of Medicine and Pharmacy, 700115 Iasi, Romania., Stoica BA; Department of Biochemistry, 'Grigore T. Popa' University of Medicine and Pharmacy, 700115 Iasi, Romania., Ciubotaru AD; Department of Pharmacology, Medical Specialties II, 'Grigore T. Popa' University of Medicine and Pharmacy, 700115 Iasi, Romania.; Department of Neurology, 'Grigore T. Popa' University of Medicine and Pharmacy, 700115 Iasi, Romania., Badescu AC; Department of Microbiology (Bacteriology, Virology) and Parasitology, 'Grigore T. Popa' University of Medicine and Pharmacy, 700115 Iasi, Romania., Bogdanici CM; Department of Ophthalmology, 'Grigore T. Popa' University of Medicine and Pharmacy, 700115 Iasi, Romania., Neagu TP; Clinical Department No. 11-Plastic, Aesthetic and Reconstructive Microsurgery, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania., Ghiciuc CM; Department of Pharmacology, Medical Specialties II, 'Grigore T. Popa' University of Medicine and Pharmacy, 700115 Iasi, Romania.
Jazyk:	angličtina
Zdroj:	Antibiotics (Basel, Switzerland) [Antibiotics (Basel)] 2023 Feb 16; Vol. 12 (2). Date of Electronic Publication: 2023 Feb 16.
DOI:	10.3390/antibiotics12020401
Abstrakt:	Mitocurcumin (a triphenylphosphonium curcumin derivative) was previously reported as a selective antitumoral compound on different cellular lines, as well as a potent bactericidal candidate. In this study, the same compound showed strong antimicrobial efficacy against different strains of methicillin-resistant Staphylococcus aureus (MRSA). The minimum inhibitory concentration was identical for all tested strains (four strains of MRSA and one strain of methicillin-sensitive Staphylococcus aureus ), suggesting a new mechanism of action compared with usual antibacterial agents. All tested strains showed a significant sensitivity in the low micromolar range for the curcumin-triphenylphosphonium derivative. This susceptibility was modulated by the menadione/glutathione addition (the addition of glutathione resulted in a significant increase in minimal inhibitory concentration from 1.95 to 3.9 uM, whereas adding menadione resulted in a decrease of 0.49 uM). The fluorescence microscopy showed a better intrabacterial accumulation for the new curcumin-triphenylphosphonium derivative compared with simple curcumin. The MitoTracker staining showed an accumulation of reactive oxygen species (ROS) for a S. pombe superoxide dismutase deleted model. All results suggest a new mechanism of action which is not influenced by the acquired resistance of MRSA. The most plausible mechanism is reactive oxygen species (ROS) overproduction after a massive intracellular accumulation of the curcumin-triphenylphosphonium derivative.
Databáze:	MEDLINE
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