Overcoming Drug Resistance in a Clinical <i>C. albicans</i> Strain Using Photoactivated Curcumin as an Adjuvant

The limited antifungal drugs available and the rise of multidrug-resistant <i>Candida</i> species have made the efforts to improve antifungal therapies paramount. To this end, our research focused on the effect of a combined treatment between chemical and photodynamic therapy (PDT) towar...

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Main Authors: Carmen-Ecaterina Leferman, Laura Stoica, Mirela Tiglis, Bogdan Alexandru Stoica, Monica Hancianu, Alin Dumitru Ciubotaru, Delia Lidia Salaru, Aida Corina Badescu, Camelia-Margareta Bogdanici, Ioan-Adrian Ciureanu, Cristina-Mihaela Ghiciuc
Format: Article
Language:English
Published: MDPI AG 2023-07-01
Series:Antibiotics
Subjects:
Online Access:https://www.mdpi.com/2079-6382/12/8/1230
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author Carmen-Ecaterina Leferman
Laura Stoica
Mirela Tiglis
Bogdan Alexandru Stoica
Monica Hancianu
Alin Dumitru Ciubotaru
Delia Lidia Salaru
Aida Corina Badescu
Camelia-Margareta Bogdanici
Ioan-Adrian Ciureanu
Cristina-Mihaela Ghiciuc
author_facet Carmen-Ecaterina Leferman
Laura Stoica
Mirela Tiglis
Bogdan Alexandru Stoica
Monica Hancianu
Alin Dumitru Ciubotaru
Delia Lidia Salaru
Aida Corina Badescu
Camelia-Margareta Bogdanici
Ioan-Adrian Ciureanu
Cristina-Mihaela Ghiciuc
author_sort Carmen-Ecaterina Leferman
collection DOAJ
description The limited antifungal drugs available and the rise of multidrug-resistant <i>Candida</i> species have made the efforts to improve antifungal therapies paramount. To this end, our research focused on the effect of a combined treatment between chemical and photodynamic therapy (PDT) towards a fluconazole-resistant clinical <i>Candida albicans</i> strain. The co-treatment of PDT and curcumin in various doses with fluconazole (FLC) had an inhibitory effect on the growth of the FLC-resistant hospital strain of <i>C. albicans</i> in both difusimetric and broth microdilution methods. The proliferation of the cells was inhibited in the presence of curcumin at 3.125 µM and FLC at 41 µM concentrations. The possible involvement of oxidative stress was analyzed by adding menadione and glutathione as a prooxidant and antioxidant, respectively. In addition, we examined the photoactivated curcumin effect on efflux pumps, a mechanism often linked to drug resistance. Nile Red accumulation assays were used to evaluate efflux pumps activity through fluorescence microscopy and spectrofluorometry. The results showed that photoactivated curcumin at 3.125 µM inhibited the transport of the fluorescent substrate that cells usually expel, indicating its potential in combating drug resistance. Overall, the findings suggest that curcumin, particularly when combined with PDT, can effectively inhibit the growth of FLC-resistant <i>C. albicans</i>, addressing the challenge of yeast resistance to azole antifungals through upregulating multidrug transporters.
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spelling doaj.art-7b880d62073b423989080ce52a9f1ffd2023-11-18T23:58:44ZengMDPI AGAntibiotics2079-63822023-07-01128123010.3390/antibiotics12081230Overcoming Drug Resistance in a Clinical <i>C. albicans</i> Strain Using Photoactivated Curcumin as an AdjuvantCarmen-Ecaterina Leferman0Laura Stoica1Mirela Tiglis2Bogdan Alexandru Stoica3Monica Hancianu4Alin Dumitru Ciubotaru5Delia Lidia Salaru6Aida Corina Badescu7Camelia-Margareta Bogdanici8Ioan-Adrian Ciureanu9Cristina-Mihaela Ghiciuc10Department of Pharmacology, Medical Specialties II, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, RomaniaDepartment of Cell and Molecular Biology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, RomaniaDepartment of Anesthesia and Intensive Care, Emergency Clinical Hospital of Bucharest, 014461 Bucharest, RomaniaDepartment of Biochemistry, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, RomaniaDepartment of Pharmacognosy, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, RomaniaDepartment of Pharmacology, Medical Specialties II, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, RomaniaInstitute of Cardiovascular Diseases, 700503 Iasi, RomaniaDepartment of Microbiology (Bacteriology, Virology) and Parasitology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, RomaniaDepartment of Ophthalmology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, RomaniaDepartment of Medical Informatics and Biostatistics, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, RomaniaDepartment of Pharmacology, Medical Specialties II, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, RomaniaThe limited antifungal drugs available and the rise of multidrug-resistant <i>Candida</i> species have made the efforts to improve antifungal therapies paramount. To this end, our research focused on the effect of a combined treatment between chemical and photodynamic therapy (PDT) towards a fluconazole-resistant clinical <i>Candida albicans</i> strain. The co-treatment of PDT and curcumin in various doses with fluconazole (FLC) had an inhibitory effect on the growth of the FLC-resistant hospital strain of <i>C. albicans</i> in both difusimetric and broth microdilution methods. The proliferation of the cells was inhibited in the presence of curcumin at 3.125 µM and FLC at 41 µM concentrations. The possible involvement of oxidative stress was analyzed by adding menadione and glutathione as a prooxidant and antioxidant, respectively. In addition, we examined the photoactivated curcumin effect on efflux pumps, a mechanism often linked to drug resistance. Nile Red accumulation assays were used to evaluate efflux pumps activity through fluorescence microscopy and spectrofluorometry. The results showed that photoactivated curcumin at 3.125 µM inhibited the transport of the fluorescent substrate that cells usually expel, indicating its potential in combating drug resistance. Overall, the findings suggest that curcumin, particularly when combined with PDT, can effectively inhibit the growth of FLC-resistant <i>C. albicans</i>, addressing the challenge of yeast resistance to azole antifungals through upregulating multidrug transporters.https://www.mdpi.com/2079-6382/12/8/1230PDTfungi<i>Candida albicans</i>curcuminantimicrobial photodynamic chemotherapyefflux pumps
spellingShingle Carmen-Ecaterina Leferman
Laura Stoica
Mirela Tiglis
Bogdan Alexandru Stoica
Monica Hancianu
Alin Dumitru Ciubotaru
Delia Lidia Salaru
Aida Corina Badescu
Camelia-Margareta Bogdanici
Ioan-Adrian Ciureanu
Cristina-Mihaela Ghiciuc
Overcoming Drug Resistance in a Clinical <i>C. albicans</i> Strain Using Photoactivated Curcumin as an Adjuvant
Antibiotics
PDT
fungi
<i>Candida albicans</i>
curcumin
antimicrobial photodynamic chemotherapy
efflux pumps
title Overcoming Drug Resistance in a Clinical <i>C. albicans</i> Strain Using Photoactivated Curcumin as an Adjuvant
title_full Overcoming Drug Resistance in a Clinical <i>C. albicans</i> Strain Using Photoactivated Curcumin as an Adjuvant
title_fullStr Overcoming Drug Resistance in a Clinical <i>C. albicans</i> Strain Using Photoactivated Curcumin as an Adjuvant
title_full_unstemmed Overcoming Drug Resistance in a Clinical <i>C. albicans</i> Strain Using Photoactivated Curcumin as an Adjuvant
title_short Overcoming Drug Resistance in a Clinical <i>C. albicans</i> Strain Using Photoactivated Curcumin as an Adjuvant
title_sort overcoming drug resistance in a clinical i c albicans i strain using photoactivated curcumin as an adjuvant
topic PDT
fungi
<i>Candida albicans</i>
curcumin
antimicrobial photodynamic chemotherapy
efflux pumps
url https://www.mdpi.com/2079-6382/12/8/1230
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