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Beauvericin counteracted multi-drug resistant Candida albicans by blocking ABC transporters
- Source :
- Synthetic and Systems Biotechnology, Vol 1, Iss 3, Pp 158-168 (2016), Tong, Y, Liu, M, Zhang, Y, Liu, X, Huang, R, Song, F, Dai, H, Ren, B, Sun, N, Pei, G, Bian, J, Jia, X-M, Huang, G, Zhou, X, Li, S, Zhang, B, Fukuda, T, Tomoda, H, Ōmura, S, Cannon, R D, Calderone, R & Zhang, L 2016, ' Beauvericin counteracted multi-drug resistant Candida albicans by blocking ABC transporters ', Synthetic and Systems Biotechnology, vol. 1, no. 3, pp. 158-168 . https://doi.org/10.1016/j.synbio.2016.10.001
- Publication Year :
- 2016
- Publisher :
- KeAi Communications Co., Ltd., 2016.
-
Abstract
- Multi-drug resistance of pathogenic microorganisms is becoming a serious threat, particularly to immunocompromised populations. The high mortality of systematic fungal infections necessitates novel antifungal drugs and therapies. Unfortunately, with traditional drug discovery approaches, only echinocandins was approved by FDA as a new class of antifungals in the past two decades. Drug efflux is one of the major contributors to multi-drug resistance, the modulator of drug efflux pumps is considered as one of the keys to conquer multi-drug resistance. In this study, we combined structure-based virtual screening and whole-cell based mechanism study, identified a natural product, beauvericin (BEA) as a drug efflux pump modulator, which can reverse the multi-drug resistant phenotype of Candida albicans by specifically blocking the ATP-binding cassette (ABC) transporters; meantime, BEA alone has fungicidal activity in vitro by elevating intracellular calcium and reactive oxygen species (ROS). It was further demonstrated by histopathological study that BEA synergizes with a sub-therapeutic dose of ketoconazole (KTC) and could cure the murine model of disseminated candidiasis. Toxicity evaluation of BEA, including acute toxicity test, Ames test, and hERG (human ether-à-go-go-related gene) test promised that BEA can be harnessed for treatment of candidiasis, especially the candidiasis caused by ABC overexpressed multi-drug resistant C. albicans.
- Subjects :
- 0301 basic medicine
Drug
Virtual screening
media_common.quotation_subject
lcsh:Biotechnology
Biomedical Engineering
ATP-binding cassette transporter
Pharmacology
Biology
Applied Microbiology and Biotechnology
Microbiology
03 medical and health sciences
SDG 3 - Good Health and Well-being
Structural Biology
lcsh:TP248.13-248.65
Candida albicans
Genetics
medicine
lcsh:QH301-705.5
media_common
Drug discovery
Disseminated Candidiasis
biology.organism_classification
Beauvericin
Corpus albicans
3. Good health
Multi-drug resistance
Synergy
030104 developmental biology
lcsh:Biology (General)
Ketoconazole
Efflux
ABC transporter
medicine.drug
Subjects
Details
- Language :
- English
- Volume :
- 1
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Synthetic and Systems Biotechnology
- Accession number :
- edsair.doi.dedup.....c9388dd7347166785c76c7643f0c49de