Proton pump inhibitors act synergistically with fluconazole against resistant Candida albicans
| العنوان: | Proton pump inhibitors act synergistically with fluconazole against resistant Candida albicans |
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| المؤلفون: | Haiying Yan, Shujuan Sun, Lei Yuan, Cuixiang Yu, Mengjiao Lu |
| المصدر: | Scientific Reports, Vol 10, Iss 1, Pp 1-10 (2020) Scientific Reports |
| بيانات النشر: | Nature Publishing Group, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, 030106 microbiology, Hyphae, Lansoprazole, lcsh:Medicine, Microbial Sensitivity Tests, Drug resistance, Pharmacology, Article, 03 medical and health sciences, Minimum inhibitory concentration, Drug Resistance, Fungal, In vivo, Candida albicans, medicine, Animals, lcsh:Science, Fluconazole, Antifungal agents, Multidisciplinary, biology, Chemistry, fungi, lcsh:R, Fungi, Drug Synergism, Proton Pump Inhibitors, biology.organism_classification, Corpus albicans, 030104 developmental biology, Biofilms, lcsh:Q, Efflux, Holometabola, medicine.drug |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 2045-2322 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::31c535733da07c879fca82bbcb4278d1Test http://link.springer.com/article/10.1038/s41598-019-57174-4Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....31c535733da07c879fca82bbcb4278d1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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