Enhanced Efflux Pump Expression in Candida Mutants Results in Decreased Manogepix Susceptibility

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 s...

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Autores principales: Liston, Sean D., Whitesell, Luke, Kapoor, Mili, Shaw, Karen Joy, Cowen, Leah E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2020
Materias:
Mechanisms of Resistance
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179633/
https://www.ncbi.nlm.nih.gov/pubmed/32179530
http://dx.doi.org/10.1128/AAC.00261-20
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author Liston, Sean D.
Whitesell, Luke
Kapoor, Mili
Shaw, Karen Joy
Cowen, Leah E.
author_facet Liston, Sean D.
Whitesell, Luke
Kapoor, Mili
Shaw, Karen Joy
Cowen, Leah E.
author_sort Liston, Sean D.
collection PubMed
description 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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spelling pubmed-71796332020-04-27 Enhanced Efflux Pump Expression in Candida Mutants Results in Decreased Manogepix Susceptibility Liston, Sean D. Whitesell, Luke Kapoor, Mili Shaw, Karen Joy Cowen, Leah E. Antimicrob Agents Chemother Mechanisms of Resistance 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. American Society for Microbiology 2020-04-21 /pmc/articles/PMC7179633/ /pubmed/32179530 http://dx.doi.org/10.1128/AAC.00261-20 Text en Copyright © 2020 Liston et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Mechanisms of Resistance
Liston, Sean D.
Whitesell, Luke
Kapoor, Mili
Shaw, Karen Joy
Cowen, Leah E.
Enhanced Efflux Pump Expression in Candida Mutants Results in Decreased Manogepix Susceptibility
title Enhanced Efflux Pump Expression in Candida Mutants Results in Decreased Manogepix Susceptibility
title_full Enhanced Efflux Pump Expression in Candida Mutants Results in Decreased Manogepix Susceptibility
title_fullStr Enhanced Efflux Pump Expression in Candida Mutants Results in Decreased Manogepix Susceptibility
title_full_unstemmed Enhanced Efflux Pump Expression in Candida Mutants Results in Decreased Manogepix Susceptibility
title_short Enhanced Efflux Pump Expression in Candida Mutants Results in Decreased Manogepix Susceptibility
title_sort enhanced efflux pump expression in candida mutants results in decreased manogepix susceptibility
topic Mechanisms of Resistance
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179633/
https://www.ncbi.nlm.nih.gov/pubmed/32179530
http://dx.doi.org/10.1128/AAC.00261-20
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