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An expanded toolkit of drug resistance cassettes for Candida glabrata, Candida auris, and Candida albicans leads to new insights into the ergosterol pathway.


ABSTRACT:

Importance

The increasing problem of drug resistance and emerging pathogens is an urgent global health problem that necessitates the development and expansion of tools for studying fungal drug resistance and pathogenesis. Prior studies in Candida glabrata, Candida auris, and Candida albicans have been mainly limited to the use of NatMX/SAT1 and HphMX/CaHyg for genetic manipulation in prototrophic strains and clinical isolates. In this study, we demonstrated that NatMX/SAT1, HphMX, KanMX, and/or BleMX drug resistance cassettes when coupled with a CRISPR-ribonucleoprotein (RNP)-based system can be efficiently utilized for deleting or modifying genes in the ergosterol pathway of C. glabrata, C. auris, and C. albicans. Moreover, the utility of these tools has provided new insights into ERG genes and their relationship to azole resistance in Candida. Overall, we have expanded the toolkit for Candida pathogens to increase the versatility of genetically modifying complex pathways involved in drug resistance and pathogenesis.

SUBMITTER: Gregor JB 

PROVIDER: S-EPMC10732037 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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An expanded toolkit of drug resistance cassettes for <i>Candida glabrata</i>, <i>Candida auris</i>, and <i>Candida albicans</i> leads to new insights into the ergosterol pathway.

Gregor Justin B JB   Gutierrez-Schultz Victor A VA   Hoda Smriti S   Baker Kortany M KM   Saha Debasmita D   Burghaze Madeline G MG   Vazquez Cynthia C   Burgei Kendra E KE   Briggs Scott D SD  

mSphere 20231106 6


<h4>Importance</h4>The increasing problem of drug resistance and emerging pathogens is an urgent global health problem that necessitates the development and expansion of tools for studying fungal drug resistance and pathogenesis. Prior studies in <i>Candida glabrata</i>, <i>Candida auris</i>, and <i>Candida albicans</i> have been mainly limited to the use of <i>NatMX/SAT1</i> and <i>HphMX/CaHyg</i> for genetic manipulation in prototrophic strains and clinical isolates. In this study, we demonstr  ...[more]

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