Fluconazole-Resistant Candida glabrata Bloodstream Isolates

In a recent review of fluconazole-resistant strains of Candida glabrata isolated from S. Korean patients, researchers identified an almost uniform mutation.  By sequencing the pleiotropic drug-resistance transcription factor they identified 1–2 additional Pdr1p amino acid substitutions (except genotype-specific Pdr1p amino acid substitutions).  These occurred in 98.5% of FR isolates from patients between 2008 & 2018.  This almost never occurred in fluconazole-sensitive strains.

Trana Discovery has tried to force mutation of susceptible strains to their microbiologic active hits to no avail.  Targeting an essential, highly modified tRNA is a unique mechanism of action(MOA).  Previously in nature fungi have not been exposed to this MOA therefore, resistance will be extremely difficult as these essential tRNA are coded for in the genome.

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