Anti-Candidal Activity of Reboxetine and Sertraline Antidepressants: Effects on Pre-Formed Biofilms
Reboxetine (REB) and sertraline (SER) are antidepressants. The antifungal potential of these drugs against planktonic Candida has been recently reported with limited data about their effects on Candidal biofilms. Biofilms are self-derived extracellular matrixes produced by the microbial population t...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/12/5/881 |
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| author | Eman Ibrahim Ahmed Ahmed M. Alhuwaydi Ahmed E. Taha Mohamed Abouelkheir |
| author_facet | Eman Ibrahim Ahmed Ahmed M. Alhuwaydi Ahmed E. Taha Mohamed Abouelkheir |
| author_sort | Eman Ibrahim Ahmed |
| collection | DOAJ |
| description | Reboxetine (REB) and sertraline (SER) are antidepressants. The antifungal potential of these drugs against planktonic Candida has been recently reported with limited data about their effects on Candidal biofilms. Biofilms are self-derived extracellular matrixes produced by the microbial population that is attached to biotic surfaces, such as vaginal and oral mucosa, or abiotic surfaces, such as biomedical devices, resulting in persistent fungal infections. The commonly prescribed antifungals, azoles, are usually less effective when biofilms are formed, and most of the prescribed antifungals are only fungistatic. Therefore, the current study investigates the antifungal potentials of REB and SER, alone and in combination with fluconazole (FLC) and itraconazole (ITR) against Candidal biofilms. Using proper controls, Candida species (<i>Candida albicans</i>, <i>C. albicans</i>; <i>Candida krusei</i>, <i>C. krusei</i>; and <i>Candida glabrata</i>, <i>C. glabrata</i>) were used to form biofilms in 96-well microplates. Serial dilutions corresponding to concentrations ranging from 2 to 4096 µg/mL of the target drugs (REB, SER, FLC, ITR) were prepared and added to the plates. Impairment of the biofilm biomass and biofilm metabolic viability was detected using the crystal violet (CV) assay and 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, respectively. In the checkerboard assay, the sessile fractional inhibitory concentration index (SFICI) was calculated to evaluate the effects of drug combinations. SER was more effective in reducing the biomass than REB for <i>C. albicans</i> and <i>C. glabrata</i>, but both were equal for <i>C. krusei</i>. For the reduction in metabolic activity in <i>C. albicans</i> and <i>C. glabrata</i>, SER had a slight advantage over REB. In <i>C. krusei</i>, REB was slightly more potent. Overall, FLC and ITR were almost equal and produced more significant reductions in metabolic activity when compared to SER and REB, except for <i>C. glabrata</i>, where SER was almost equal to FLC. Synergism was detected between REB + FLC and REB + ITR against biofilm cells of <i>C. albicans</i>. Synergism was detected between REB + ITR against biofilm cells of <i>C. krusei</i>. Synergism was detected between REB + FLC and REB + ITR against biofilm cells of <i>C. albicans</i>, <i>C. krusei</i>, and <i>C. glabrata</i>. The results of the present study support the potential of SER and REB as anti-Candidal biofilm agents that are beneficial as a new antifungal to combat Candidal resistance. |
| first_indexed | 2024-03-11T04:00:10Z |
| format | Article |
| id | doaj.art-c6f6c89888fb44b5b194b59298748f0b |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-11T04:00:10Z |
| publishDate | 2023-05-01 |
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| series | Antibiotics |
| spelling | doaj.art-c6f6c89888fb44b5b194b59298748f0b2023-11-18T00:12:40ZengMDPI AGAntibiotics2079-63822023-05-0112588110.3390/antibiotics12050881Anti-Candidal Activity of Reboxetine and Sertraline Antidepressants: Effects on Pre-Formed BiofilmsEman Ibrahim Ahmed0Ahmed M. Alhuwaydi1Ahmed E. Taha2Mohamed Abouelkheir3Department of Pharmacology and Therapeutics, College of Medicine, Jouf University, Sakaka 72388, Saudi ArabiaDepartment of Internal Medicine, College of Medicine, Jouf University, Sakaka 72388, Saudi ArabiaMicrobiology and Immunology Unit, Department of Pathology, College of Medicine, Jouf University, Sakaka 72388, Saudi ArabiaDepartment of Pharmacology and Therapeutics, College of Medicine, Jouf University, Sakaka 72388, Saudi ArabiaReboxetine (REB) and sertraline (SER) are antidepressants. The antifungal potential of these drugs against planktonic Candida has been recently reported with limited data about their effects on Candidal biofilms. Biofilms are self-derived extracellular matrixes produced by the microbial population that is attached to biotic surfaces, such as vaginal and oral mucosa, or abiotic surfaces, such as biomedical devices, resulting in persistent fungal infections. The commonly prescribed antifungals, azoles, are usually less effective when biofilms are formed, and most of the prescribed antifungals are only fungistatic. Therefore, the current study investigates the antifungal potentials of REB and SER, alone and in combination with fluconazole (FLC) and itraconazole (ITR) against Candidal biofilms. Using proper controls, Candida species (<i>Candida albicans</i>, <i>C. albicans</i>; <i>Candida krusei</i>, <i>C. krusei</i>; and <i>Candida glabrata</i>, <i>C. glabrata</i>) were used to form biofilms in 96-well microplates. Serial dilutions corresponding to concentrations ranging from 2 to 4096 µg/mL of the target drugs (REB, SER, FLC, ITR) were prepared and added to the plates. Impairment of the biofilm biomass and biofilm metabolic viability was detected using the crystal violet (CV) assay and 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, respectively. In the checkerboard assay, the sessile fractional inhibitory concentration index (SFICI) was calculated to evaluate the effects of drug combinations. SER was more effective in reducing the biomass than REB for <i>C. albicans</i> and <i>C. glabrata</i>, but both were equal for <i>C. krusei</i>. For the reduction in metabolic activity in <i>C. albicans</i> and <i>C. glabrata</i>, SER had a slight advantage over REB. In <i>C. krusei</i>, REB was slightly more potent. Overall, FLC and ITR were almost equal and produced more significant reductions in metabolic activity when compared to SER and REB, except for <i>C. glabrata</i>, where SER was almost equal to FLC. Synergism was detected between REB + FLC and REB + ITR against biofilm cells of <i>C. albicans</i>. Synergism was detected between REB + ITR against biofilm cells of <i>C. krusei</i>. Synergism was detected between REB + FLC and REB + ITR against biofilm cells of <i>C. albicans</i>, <i>C. krusei</i>, and <i>C. glabrata</i>. The results of the present study support the potential of SER and REB as anti-Candidal biofilm agents that are beneficial as a new antifungal to combat Candidal resistance.https://www.mdpi.com/2079-6382/12/5/881azolesbiomasscandidiasis<i>C. albicans</i><i>C. glabrata</i><i>C. krusei</i> |
| spellingShingle | Eman Ibrahim Ahmed Ahmed M. Alhuwaydi Ahmed E. Taha Mohamed Abouelkheir Anti-Candidal Activity of Reboxetine and Sertraline Antidepressants: Effects on Pre-Formed Biofilms Antibiotics azoles biomass candidiasis <i>C. albicans</i> <i>C. glabrata</i> <i>C. krusei</i> |
| title | Anti-Candidal Activity of Reboxetine and Sertraline Antidepressants: Effects on Pre-Formed Biofilms |
| title_full | Anti-Candidal Activity of Reboxetine and Sertraline Antidepressants: Effects on Pre-Formed Biofilms |
| title_fullStr | Anti-Candidal Activity of Reboxetine and Sertraline Antidepressants: Effects on Pre-Formed Biofilms |
| title_full_unstemmed | Anti-Candidal Activity of Reboxetine and Sertraline Antidepressants: Effects on Pre-Formed Biofilms |
| title_short | Anti-Candidal Activity of Reboxetine and Sertraline Antidepressants: Effects on Pre-Formed Biofilms |
| title_sort | anti candidal activity of reboxetine and sertraline antidepressants effects on pre formed biofilms |
| topic | azoles biomass candidiasis <i>C. albicans</i> <i>C. glabrata</i> <i>C. krusei</i> |
| url | https://www.mdpi.com/2079-6382/12/5/881 |
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