Overcoming Drug Resistance in a Clinical C. albicans Strain Using Photoactivated Curcumin as an Adjuvant
The limited antifungal drugs available and the rise of multidrug-resistant Candida 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-re...
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Published in | Antibiotics (Basel) Vol. 12; no. 8; p. 1230 |
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Main Authors | , , , , , , , , , , |
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Language | English |
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25.07.2023
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Abstract | The limited antifungal drugs available and the rise of multidrug-resistant Candida 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 Candida albicans 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 C. albicans 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 C. albicans, addressing the challenge of yeast resistance to azole antifungals through upregulating multidrug transporters. |
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AbstractList | The limited antifungal drugs available and the rise of multidrug-resistant Candida 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 Candida albicans 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 C. albicans 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 C. albicans, addressing the challenge of yeast resistance to azole antifungals through upregulating multidrug transporters. The limited antifungal drugs available and the rise of multidrug-resistant Candida 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 Candida albicans 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 C. albicans 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 C. albicans , addressing the challenge of yeast resistance to azole antifungals through upregulating multidrug transporters. |
Author | Ciubotaru, Alin Dumitru Salaru, Delia Lidia Bogdanici, Camelia-Margareta Leferman, Carmen-Ecaterina Badescu, Aida Corina Stoica, Bogdan Alexandru Stoica, Laura Hancianu, Monica Ciureanu, Ioan-Adrian Ghiciuc, Cristina-Mihaela Tiglis, Mirela |
AuthorAffiliation | 8 Institute of Cardiovascular Diseases, 700503 Iasi, Romania 1 Department of Pharmacology, Medical Specialties II, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; carmen-ecaterina.leferman@umfiasi.ro (C.-E.L.) 7 Department of Neurology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania 10 Department of Medical Informatics and Biostatistics, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania 5 Department of Biochemistry, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania 9 Department of Microbiology (Bacteriology, Virology) and Parasitology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania 2 Department of Ophthalmology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania 4 Department of Anesthesia and Intensive Care, Emergency Clinical Hospital of Bucharest, 014461 Bucharest, Romania 3 Department of Cell and Molecular Biology, “Grigore T. Po |
AuthorAffiliation_xml | – name: 4 Department of Anesthesia and Intensive Care, Emergency Clinical Hospital of Bucharest, 014461 Bucharest, Romania – name: 7 Department of Neurology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania – name: 10 Department of Medical Informatics and Biostatistics, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania – name: 5 Department of Biochemistry, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania – name: 8 Institute of Cardiovascular Diseases, 700503 Iasi, Romania – name: 1 Department of Pharmacology, Medical Specialties II, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; carmen-ecaterina.leferman@umfiasi.ro (C.-E.L.) – name: 3 Department of Cell and Molecular Biology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania – name: 6 Department of Pharmacognosy, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania – name: 2 Department of Ophthalmology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania – name: 9 Department of Microbiology (Bacteriology, Virology) and Parasitology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania |
Author_xml | – sequence: 1 givenname: Carmen-Ecaterina surname: Leferman fullname: Leferman, Carmen-Ecaterina – sequence: 2 givenname: Laura surname: Stoica fullname: Stoica, Laura – sequence: 3 givenname: Mirela orcidid: 0000-0003-3542-3217 surname: Tiglis fullname: Tiglis, Mirela – sequence: 4 givenname: Bogdan Alexandru surname: Stoica fullname: Stoica, Bogdan Alexandru – sequence: 5 givenname: Monica surname: Hancianu fullname: Hancianu, Monica – sequence: 6 givenname: Alin Dumitru surname: Ciubotaru fullname: Ciubotaru, Alin Dumitru – sequence: 7 givenname: Delia Lidia surname: Salaru fullname: Salaru, Delia Lidia – sequence: 8 givenname: Aida Corina surname: Badescu fullname: Badescu, Aida Corina – sequence: 9 givenname: Camelia-Margareta orcidid: 0000-0002-9542-7714 surname: Bogdanici fullname: Bogdanici, Camelia-Margareta – sequence: 10 givenname: Ioan-Adrian orcidid: 0000-0002-9689-8569 surname: Ciureanu fullname: Ciureanu, Ioan-Adrian – sequence: 11 givenname: Cristina-Mihaela orcidid: 0000-0003-1791-0425 surname: Ghiciuc fullname: Ghiciuc, Cristina-Mihaela |
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Snippet | The limited antifungal drugs available and the rise of multidrug-resistant Candida species have made the efforts to improve antifungal therapies paramount. To... The limited antifungal drugs available and the rise of multidrug-resistant Candida species have made the efforts to improve antifungal therapies paramount. To... |
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SubjectTerms | Antifungal agents antimicrobial photodynamic chemotherapy Antioxidants Biofilms Candida albicans Cell growth Cell proliferation Combined treatment Curcumin Drug resistance Efflux efflux pumps Fluconazole Fluorescence Fluorescence microscopy Fluorescence spectroscopy Fungal infections fungi Fungicides Glutathione Health services Light emitting diodes Menadione Multidrug resistance Oxidative stress PDT Photodynamic therapy Pumps Toxicity Yeast Yeasts |
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Title | Overcoming Drug Resistance in a Clinical C. albicans Strain Using Photoactivated Curcumin as an Adjuvant |
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