Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
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 |
_version_ | 1784893695145803776 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9952693 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT lefermancarmenecaterina mitochondriatargetedcurcuminapotentantibacterialagentagainstmethicillinresistantstaphylococcusaureuswithapossibleintracellularrosaccumulationasthemechanismofaction AT stoicalaura mitochondriatargetedcurcuminapotentantibacterialagentagainstmethicillinresistantstaphylococcusaureuswithapossibleintracellularrosaccumulationasthemechanismofaction AT stoicabogdanalexandru mitochondriatargetedcurcuminapotentantibacterialagentagainstmethicillinresistantstaphylococcusaureuswithapossibleintracellularrosaccumulationasthemechanismofaction AT ciubotarualindumitru mitochondriatargetedcurcuminapotentantibacterialagentagainstmethicillinresistantstaphylococcusaureuswithapossibleintracellularrosaccumulationasthemechanismofaction AT badescuaidacorina mitochondriatargetedcurcuminapotentantibacterialagentagainstmethicillinresistantstaphylococcusaureuswithapossibleintracellularrosaccumulationasthemechanismofaction AT bogdanicicameliamargareta mitochondriatargetedcurcuminapotentantibacterialagentagainstmethicillinresistantstaphylococcusaureuswithapossibleintracellularrosaccumulationasthemechanismofaction AT neagutiberiupaul mitochondriatargetedcurcuminapotentantibacterialagentagainstmethicillinresistantstaphylococcusaureuswithapossibleintracellularrosaccumulationasthemechanismofaction AT ghiciuccristinamihaela mitochondriatargetedcurcuminapotentantibacterialagentagainstmethicillinresistantstaphylococcusaureuswithapossibleintracellularrosaccumulationasthemechanismofaction |