Pyrogallol and Fluconazole Interact Synergistically In Vitro against Candida glabrata through an Efflux-Associated Mechanism
Candida glabrata is currently the first or second most commonly encountered non-albicans Candida species worldwide. The potential severity of Candida resistance mandates the discovery of novel antifungal agents, including those that can be used in combination therapies. In this study, we evaluated t...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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American Society for Microbiology
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373228/ https://www.ncbi.nlm.nih.gov/pubmed/33875436 http://dx.doi.org/10.1128/AAC.00100-21 |
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author | Yao, Dongting Zhang, Guanyi Chen, Weiqin Chen, Jia Li, Zhen Zheng, Xin Yin, Hongmei Hu, Xiaobo |
author_facet | Yao, Dongting Zhang, Guanyi Chen, Weiqin Chen, Jia Li, Zhen Zheng, Xin Yin, Hongmei Hu, Xiaobo |
author_sort | Yao, Dongting |
collection | PubMed |
description | Candida glabrata is currently the first or second most commonly encountered non-albicans Candida species worldwide. The potential severity of Candida resistance mandates the discovery of novel antifungal agents, including those that can be used in combination therapies. In this study, we evaluated the in vitro interactions of pyrogallol (PG) and azole drugs against 22 clinical C. glabrata isolates. The potential mechanism underlying the synergism between PG and fluconazole (FLC) was investigated by the rhodamine 6G efflux method and quantitative reverse transcription (qRT)-PCR analysis. In susceptibility tests, PG showed strong synergism with FLC, itraconazole (ITC), and voriconazole (VRC), with fractional inhibitory concentration index values of 0.18 to 0.375 for PG+FLC, 0.250 to 0.750 for PG+ITC, and 0.141 to 0.750 for PG+VRC. Cells grown in the presence of PG+FLC exhibited reduced rhodamine 6G extrusion and significantly downregulated expression of the efflux-related genes CgCDR1, CgCDR2, and CgPDR1 compared with cells grown in the presence of PG or FLC alone. PG did not potentiate FLC when tested against a ΔCgpdr1 strain. Restoration of a functional CgPDR1 allele also restored the synergism. These results indicate that PG is an antifungal agent that synergistically potentiates the activity of azoles. Furthermore, PG appears to exert its effects by inhibiting efflux pumps and downregulating CgCDR1, CgCDR2, and CgPDR1, with CgPDR1 probably playing a crucial role in this process. |
format | Online Article Text |
id | pubmed-8373228 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-83732282021-12-17 Pyrogallol and Fluconazole Interact Synergistically In Vitro against Candida glabrata through an Efflux-Associated Mechanism Yao, Dongting Zhang, Guanyi Chen, Weiqin Chen, Jia Li, Zhen Zheng, Xin Yin, Hongmei Hu, Xiaobo Antimicrob Agents Chemother Mechanisms of Resistance Candida glabrata is currently the first or second most commonly encountered non-albicans Candida species worldwide. The potential severity of Candida resistance mandates the discovery of novel antifungal agents, including those that can be used in combination therapies. In this study, we evaluated the in vitro interactions of pyrogallol (PG) and azole drugs against 22 clinical C. glabrata isolates. The potential mechanism underlying the synergism between PG and fluconazole (FLC) was investigated by the rhodamine 6G efflux method and quantitative reverse transcription (qRT)-PCR analysis. In susceptibility tests, PG showed strong synergism with FLC, itraconazole (ITC), and voriconazole (VRC), with fractional inhibitory concentration index values of 0.18 to 0.375 for PG+FLC, 0.250 to 0.750 for PG+ITC, and 0.141 to 0.750 for PG+VRC. Cells grown in the presence of PG+FLC exhibited reduced rhodamine 6G extrusion and significantly downregulated expression of the efflux-related genes CgCDR1, CgCDR2, and CgPDR1 compared with cells grown in the presence of PG or FLC alone. PG did not potentiate FLC when tested against a ΔCgpdr1 strain. Restoration of a functional CgPDR1 allele also restored the synergism. These results indicate that PG is an antifungal agent that synergistically potentiates the activity of azoles. Furthermore, PG appears to exert its effects by inhibiting efflux pumps and downregulating CgCDR1, CgCDR2, and CgPDR1, with CgPDR1 probably playing a crucial role in this process. American Society for Microbiology 2021-06-17 /pmc/articles/PMC8373228/ /pubmed/33875436 http://dx.doi.org/10.1128/AAC.00100-21 Text en Copyright © 2021 Yao et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Mechanisms of Resistance Yao, Dongting Zhang, Guanyi Chen, Weiqin Chen, Jia Li, Zhen Zheng, Xin Yin, Hongmei Hu, Xiaobo Pyrogallol and Fluconazole Interact Synergistically In Vitro against Candida glabrata through an Efflux-Associated Mechanism |
title | Pyrogallol and Fluconazole Interact Synergistically In Vitro against Candida glabrata through an Efflux-Associated Mechanism |
title_full | Pyrogallol and Fluconazole Interact Synergistically In Vitro against Candida glabrata through an Efflux-Associated Mechanism |
title_fullStr | Pyrogallol and Fluconazole Interact Synergistically In Vitro against Candida glabrata through an Efflux-Associated Mechanism |
title_full_unstemmed | Pyrogallol and Fluconazole Interact Synergistically In Vitro against Candida glabrata through an Efflux-Associated Mechanism |
title_short | Pyrogallol and Fluconazole Interact Synergistically In Vitro against Candida glabrata through an Efflux-Associated Mechanism |
title_sort | pyrogallol and fluconazole interact synergistically in vitro against candida glabrata through an efflux-associated mechanism |
topic | Mechanisms of Resistance |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373228/ https://www.ncbi.nlm.nih.gov/pubmed/33875436 http://dx.doi.org/10.1128/AAC.00100-21 |
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