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Revealing the astragalin mode of anticandidal action

Due to limited arsenal of systemically available antifungal agents, infections caused by Candida albicans are difficult to treat and the emergence of drug-resistant strains present a major challenge to the clinicians worldwide. Hence further exploration of potential novel and effective antifungal dr...

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Autores principales: Ivanov, Marija, Kannan, Abhilash, Stojkovic, Dejan, Glamoclija, Jasmina, Golic Grdadolnik, Simona, Sanglard, Dominique, Sokovic, Marina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Leibniz Research Centre for Working Environment and Human Factors 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726490/
https://www.ncbi.nlm.nih.gov/pubmed/33312106
http://dx.doi.org/10.17179/excli2020-2987
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author Ivanov, Marija
Kannan, Abhilash
Stojkovic, Dejan
Glamoclija, Jasmina
Golic Grdadolnik, Simona
Sanglard, Dominique
Sokovic, Marina
author_facet Ivanov, Marija
Kannan, Abhilash
Stojkovic, Dejan
Glamoclija, Jasmina
Golic Grdadolnik, Simona
Sanglard, Dominique
Sokovic, Marina
author_sort Ivanov, Marija
collection PubMed
description Due to limited arsenal of systemically available antifungal agents, infections caused by Candida albicans are difficult to treat and the emergence of drug-resistant strains present a major challenge to the clinicians worldwide. Hence further exploration of potential novel and effective antifungal drugs is required. In this study we have explored the potential of a flavonoid, astragalin, in controlling the growth of C. albicans, in both planktonic and biofilm forms by microdilution method; and in regulating the morphological switch between yeast and hyphal growth. Astragalin ability to interfere with membrane integrity, ergosterol synthesis and its role in the regulation of genes encoding for efflux pumps has been addressed. In our study, astragalin treatment produced good antimicrobial and significant antibiofilm activity. Anticandidal activity of astragalin was not related to ERG11 downregulation, neither to direct binding to CYP51 enzyme nor was linked to membrane ergosterol assembly. Instead, astragalin treatment resulted in reduced expression of CDR1 and also affected cell membrane integrity without causing cytotoxic effect on human gingival fibroblast cells. Considering that astragalin-mediated decreased expression of efflux pumps increases the concentration of antifungal drug inside the fungal cells, a combinatorial treatment with this agent could be explored as a novel therapeutic option for candidiasis.
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spelling pubmed-77264902020-12-10 Revealing the astragalin mode of anticandidal action Ivanov, Marija Kannan, Abhilash Stojkovic, Dejan Glamoclija, Jasmina Golic Grdadolnik, Simona Sanglard, Dominique Sokovic, Marina EXCLI J Original Article Due to limited arsenal of systemically available antifungal agents, infections caused by Candida albicans are difficult to treat and the emergence of drug-resistant strains present a major challenge to the clinicians worldwide. Hence further exploration of potential novel and effective antifungal drugs is required. In this study we have explored the potential of a flavonoid, astragalin, in controlling the growth of C. albicans, in both planktonic and biofilm forms by microdilution method; and in regulating the morphological switch between yeast and hyphal growth. Astragalin ability to interfere with membrane integrity, ergosterol synthesis and its role in the regulation of genes encoding for efflux pumps has been addressed. In our study, astragalin treatment produced good antimicrobial and significant antibiofilm activity. Anticandidal activity of astragalin was not related to ERG11 downregulation, neither to direct binding to CYP51 enzyme nor was linked to membrane ergosterol assembly. Instead, astragalin treatment resulted in reduced expression of CDR1 and also affected cell membrane integrity without causing cytotoxic effect on human gingival fibroblast cells. Considering that astragalin-mediated decreased expression of efflux pumps increases the concentration of antifungal drug inside the fungal cells, a combinatorial treatment with this agent could be explored as a novel therapeutic option for candidiasis. Leibniz Research Centre for Working Environment and Human Factors 2020-10-29 /pmc/articles/PMC7726490/ /pubmed/33312106 http://dx.doi.org/10.17179/excli2020-2987 Text en Copyright © 2020 Ivanov et al. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (http://creativecommons.org/licenses/by/4.0/) You are free to copy, distribute and transmit the work, provided the original author and source are credited.
spellingShingle Original Article
Ivanov, Marija
Kannan, Abhilash
Stojkovic, Dejan
Glamoclija, Jasmina
Golic Grdadolnik, Simona
Sanglard, Dominique
Sokovic, Marina
Revealing the astragalin mode of anticandidal action
title Revealing the astragalin mode of anticandidal action
title_full Revealing the astragalin mode of anticandidal action
title_fullStr Revealing the astragalin mode of anticandidal action
title_full_unstemmed Revealing the astragalin mode of anticandidal action
title_short Revealing the astragalin mode of anticandidal action
title_sort revealing the astragalin mode of anticandidal action
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726490/
https://www.ncbi.nlm.nih.gov/pubmed/33312106
http://dx.doi.org/10.17179/excli2020-2987
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