Evaluation of Resistance Development to the Gwt1 Inhibitor Manogepix (APX001A) in Candida Species.

ABSTRACT: Manogepix (MGX) targets the conserved fungal Gwt1 enzyme required for acylation of inositol early in the glycosylphosphatidylinositol biosynthesis pathway. The prodrug fosmanogepix is currently in clinical development for the treatment of invasive fungal infections. We determined that the median frequencies of spontaneous mutations conferring reduced susceptibility to MGX in Candida albicans, C. glabrata, and C. parapsilosis ranged from 3 × 10^-8 to <1.85 × 10^-8 Serial passage on agar identified mutants of C. albicans and C. parapsilosis with reduced susceptibility to MGX; however, this methodology did not result in C. glabrata mutants with reduced susceptibility. Similarly, serial passage in broth resulted in ≤2-fold changes i

SUBMITTER: Kapoor M 

PROVIDER: S-EPMC7187586 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature