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

• Main Authors: Carmen-Ecaterina Leferman (Author), Laura Stoica (Author), Bogdan Alexandru Stoica (Author), Alin Dumitru Ciubotaru (Author), Aida Corina Badescu (Author), Camelia-Margareta Bogdanici (Author), Tiberiu Paul Neagu (Author), Cristina-Mihaela Ghiciuc (Author)
• Format: Book
• Published: MDPI AG, 2023-02-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/antibiotics12020401; 2079-6382
• Keywords: mitocurcumin; methicillin-resistant <i>Staphylococcus aureus</i>; redox mechanism; curcumin; triphenylphosphonium derivatives; Therapeutics. Pharmacology; RM1-950
• Source: Antibiotics, Vol 12, Iss 2, p 401 (2023)

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 <i>Staphylococcus aureus</i> (MRSA). The minimum inhibitory concentration was identical for all tested strains (four strains of MRSA and one strain of methicillin-sensitive <i>Staphylococcus aureus</i>), 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 <i>S. pombe</i> 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.