A new MRR1 gain-of-function mutation involved in cross-resistance to antifungal agents in the fungal priority pathogen Candida parapsilosis.

A novel G982E mutation in MRR1 causes high-level fluconazole resistance and treatment failure in Candida parapsilosis.

• Why it matters: Rising fluconazole resistance in Candida parapsilosis threatens effective clinical management of invasive candidiasis, highlighting the need to understand resistance mechanisms.
• What they did: Researchers used CRISPR-Cas9 to introduce the G982E mutation into susceptible strains and tested antifungal susceptibility and virulence in vitro and in vivo with a Galleria mellonella model.
• The result: The G982E mutation increased fluconazole MICs over 256 μg/mL, caused treatment failure, and reduced virulence, emphasizing its role in resistance and potential impact on fungal fitness.