title: Candida glabrata mutants demonstrating paradoxical reduced caspofungin susceptibility but increased micafungin susceptibility.
abstract: Echinocandins, including caspofungin (CSP) and micafungin (MCF), are highly active versus Candida glabrata (MIC of ≤0.06 μg/ml). True resistance (MIC of ≥1 μg/ml) is a rare event and strictly associated with mutations in β-1,3-glucan synthase gene FKS1 or FKS2. In contrast, we show here that mutants exhibiting reduced susceptibility to CSP (CRS; MICs of 0.12 to 0.5 μg/ml) are readily selected in vitro and, paradoxically, demonstrate increased susceptibility to MCF (MIS) ranging from 4- to 32-fold. CRS-MIS mutants were generated from all 10 C. glabrata strains tested and were tentatively identified within a collection of clinical isolates. Intriguingly, sequencing and gene disruption demonstrated that CRS-MIS is Fks independent.
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
authors.forename: Kelley R
authors.initials: KR
authors.lastname: Healey
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Katiyar
authors.forename: Mariana
authors.initials: M
authors.lastname: Castanheira
authors.forename: Michael A
authors.initials: MA
authors.lastname: Pfaller
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Edlind
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D041221:Candida glabrata / Q000187:drug effects* / Q000235:genetics*; D000077336:Caspofungin; D025141:Drug Resistance, Fungal / Q000235:genetics; D054714:Echinocandins / Q000494:pharmacology*; D005656:Fungal Proteins / Q000235:genetics; D055666:Lipopeptides / Q000494:pharmacology*; D000077551:Micafungin; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation; D017422:Sequence Analysis, DNA
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D005656:Fungal Proteins; D055666:Lipopeptides; D000077336:Caspofungin; D000077551:Micafungin