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Proton pump inhibitors act synergistically with fluconazole against resistant Candida albicans
The incidence of resistant Candida isolates, especially Candida albicans, has increased continuously. To overcome the resistance, research on antifungal agent sensitizers has attracted considerable attention. Omeprazole and lansoprazole were found to inhibit the growth of sensitive C. albicans and h...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965112/ https://www.ncbi.nlm.nih.gov/pubmed/31949170 http://dx.doi.org/10.1038/s41598-019-57174-4 |
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author | Lu, Mengjiao Yan, Haiying Yu, Cuixiang Yuan, Lei Sun, Shujuan |
author_facet | Lu, Mengjiao Yan, Haiying Yu, Cuixiang Yuan, Lei Sun, Shujuan |
author_sort | Lu, Mengjiao |
collection | PubMed |
description | The incidence of resistant Candida isolates, especially Candida albicans, has increased continuously. To overcome the resistance, research on antifungal agent sensitizers has attracted considerable attention. Omeprazole and lansoprazole were found to inhibit the growth of sensitive C. albicans and hyphae formation in a high dose, respectively. This study aimed to determine the interactions of common clinically proton pump inhibitors (PPIs) and fluconazole both in vitro and in vivo and to further explore the possible mechanisms. In vitro, the tested PPIs all acted synergistically with fluconazole against both resistant C. albicans planktonic cells and biofilms preformed for ≤12 h with the minimum inhibitory concentration of fluconazole decreased from >512 μg/mL to 1–4 μg/mL. In vivo, PPIs plus fluconazole prolonged the survival rate of infected Galleria mellonella larvae by two-fold compared with that for the fluconazole monotherapy group and significantly reduced the tissue damage of infected larvae. Mechanism studies showed that PPIs significantly suppressed efflux pump activity, which is the common resistance mechanism of C. albicans, and significantly inhibited the virulence factors: phospholipase activity and morphology switching. These findings will provide new insights into antifungal agent discovery and potential approaches for the treatment of candidiasis caused by resistant C. albicans. |
format | Online Article Text |
id | pubmed-6965112 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-69651122020-01-23 Proton pump inhibitors act synergistically with fluconazole against resistant Candida albicans Lu, Mengjiao Yan, Haiying Yu, Cuixiang Yuan, Lei Sun, Shujuan Sci Rep Article The incidence of resistant Candida isolates, especially Candida albicans, has increased continuously. To overcome the resistance, research on antifungal agent sensitizers has attracted considerable attention. Omeprazole and lansoprazole were found to inhibit the growth of sensitive C. albicans and hyphae formation in a high dose, respectively. This study aimed to determine the interactions of common clinically proton pump inhibitors (PPIs) and fluconazole both in vitro and in vivo and to further explore the possible mechanisms. In vitro, the tested PPIs all acted synergistically with fluconazole against both resistant C. albicans planktonic cells and biofilms preformed for ≤12 h with the minimum inhibitory concentration of fluconazole decreased from >512 μg/mL to 1–4 μg/mL. In vivo, PPIs plus fluconazole prolonged the survival rate of infected Galleria mellonella larvae by two-fold compared with that for the fluconazole monotherapy group and significantly reduced the tissue damage of infected larvae. Mechanism studies showed that PPIs significantly suppressed efflux pump activity, which is the common resistance mechanism of C. albicans, and significantly inhibited the virulence factors: phospholipase activity and morphology switching. These findings will provide new insights into antifungal agent discovery and potential approaches for the treatment of candidiasis caused by resistant C. albicans. Nature Publishing Group UK 2020-01-16 /pmc/articles/PMC6965112/ /pubmed/31949170 http://dx.doi.org/10.1038/s41598-019-57174-4 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Lu, Mengjiao Yan, Haiying Yu, Cuixiang Yuan, Lei Sun, Shujuan Proton pump inhibitors act synergistically with fluconazole against resistant Candida albicans |
title | Proton pump inhibitors act synergistically with fluconazole against resistant Candida albicans |
title_full | Proton pump inhibitors act synergistically with fluconazole against resistant Candida albicans |
title_fullStr | Proton pump inhibitors act synergistically with fluconazole against resistant Candida albicans |
title_full_unstemmed | Proton pump inhibitors act synergistically with fluconazole against resistant Candida albicans |
title_short | Proton pump inhibitors act synergistically with fluconazole against resistant Candida albicans |
title_sort | proton pump inhibitors act synergistically with fluconazole against resistant candida albicans |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965112/ https://www.ncbi.nlm.nih.gov/pubmed/31949170 http://dx.doi.org/10.1038/s41598-019-57174-4 |
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