期刊
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
卷 64, 期 5, 页码 -出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.00261-20
关键词
APX001; fosmanogepix; manogepix; APX001A; Gwt1; antifungal; GPI anchor; glycosylphosphatidylinositol; antifungal therapy; efflux
资金
- Amplyx
- NSERC [516840-2018]
Manogepix is a broad-spectrum antifungal agent that inhibits glycosylphosphatidylinositol (GPI) anchor biosynthesis. Using whole-genome sequencing, we characterized two efflux-mediated mechanisms in the fungal pathogens Candida albicans and Candida parapsilosis that resulted in decreased manogepix susceptibility. In C. albicans, a gain-of-function mutation in the transcription factor gene ZCF29 activated expression of ATP-binding cassette transporter genes CDR11 and SNQ2. In C. parapsilosis, a mitochondrial deletion activated expression of the major facilitator superfamily transporter gene MDR1.
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