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

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 methicilli...

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Autores principales: Leferman, Carmen-Ecaterina, Stoica, Laura, Stoica, Bogdan Alexandru, Ciubotaru, Alin Dumitru, Badescu, Aida Corina, Bogdanici, Camelia-Margareta, Neagu, Tiberiu Paul, Ghiciuc, Cristina-Mihaela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9952693/
https://www.ncbi.nlm.nih.gov/pubmed/36830311
http://dx.doi.org/10.3390/antibiotics12020401
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author Leferman, Carmen-Ecaterina
Stoica, Laura
Stoica, Bogdan Alexandru
Ciubotaru, Alin Dumitru
Badescu, Aida Corina
Bogdanici, Camelia-Margareta
Neagu, Tiberiu Paul
Ghiciuc, Cristina-Mihaela
author_facet Leferman, Carmen-Ecaterina
Stoica, Laura
Stoica, Bogdan Alexandru
Ciubotaru, Alin Dumitru
Badescu, Aida Corina
Bogdanici, Camelia-Margareta
Neagu, Tiberiu Paul
Ghiciuc, Cristina-Mihaela
author_sort Leferman, Carmen-Ecaterina
collection PubMed
description 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.
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spelling pubmed-99526932023-02-25 Mitochondria-Targeted Curcumin: A Potent Antibacterial Agent against Methicillin-Resistant Staphylococcus aureus with a Possible Intracellular ROS Accumulation as the Mechanism of Action Leferman, Carmen-Ecaterina Stoica, Laura Stoica, Bogdan Alexandru Ciubotaru, Alin Dumitru Badescu, Aida Corina Bogdanici, Camelia-Margareta Neagu, Tiberiu Paul Ghiciuc, Cristina-Mihaela Antibiotics (Basel) Article 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. MDPI 2023-02-16 /pmc/articles/PMC9952693/ /pubmed/36830311 http://dx.doi.org/10.3390/antibiotics12020401 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Leferman, Carmen-Ecaterina
Stoica, Laura
Stoica, Bogdan Alexandru
Ciubotaru, Alin Dumitru
Badescu, Aida Corina
Bogdanici, Camelia-Margareta
Neagu, Tiberiu Paul
Ghiciuc, Cristina-Mihaela
Mitochondria-Targeted Curcumin: A Potent Antibacterial Agent against Methicillin-Resistant Staphylococcus aureus with a Possible Intracellular ROS Accumulation as the Mechanism of Action
title Mitochondria-Targeted Curcumin: A Potent Antibacterial Agent against Methicillin-Resistant Staphylococcus aureus with a Possible Intracellular ROS Accumulation as the Mechanism of Action
title_full Mitochondria-Targeted Curcumin: A Potent Antibacterial Agent against Methicillin-Resistant Staphylococcus aureus with a Possible Intracellular ROS Accumulation as the Mechanism of Action
title_fullStr Mitochondria-Targeted Curcumin: A Potent Antibacterial Agent against Methicillin-Resistant Staphylococcus aureus with a Possible Intracellular ROS Accumulation as the Mechanism of Action
title_full_unstemmed Mitochondria-Targeted Curcumin: A Potent Antibacterial Agent against Methicillin-Resistant Staphylococcus aureus with a Possible Intracellular ROS Accumulation as the Mechanism of Action
title_short Mitochondria-Targeted Curcumin: A Potent Antibacterial Agent against Methicillin-Resistant Staphylococcus aureus with a Possible Intracellular ROS Accumulation as the Mechanism of Action
title_sort mitochondria-targeted curcumin: a potent antibacterial agent against methicillin-resistant staphylococcus aureus with a possible intracellular ros accumulation as the mechanism of action
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9952693/
https://www.ncbi.nlm.nih.gov/pubmed/36830311
http://dx.doi.org/10.3390/antibiotics12020401
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