Enhanced Efflux Pump Expression in <i>Candida</i> Mutants Results in Decreased Manogepix Susceptibility
Sean D. Liston, Luke Whitesell, Mili Kapoor, Karen Joy Shaw, Leah E. Cowen
Abstract
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 .
Topics & Concepts
EffluxCandida albicansMutantCandida parapsilosisBiologyGeneMicrobiologyCorpus albicansTranscription factorTransporterATP-binding cassette transporterGeneticsAntifungal resistance and susceptibilityFungal Infections and StudiesCarbohydrate Chemistry and Synthesis