Caspofungin paradoxical growth in <i>Candida albicans</i> requires stress pathway activation and promotes unstable echinocandin resistance mediated by aneuploidy.

ABSTRACT: Paradoxical growth (PG) is a counterintuitive phenomenon in which otherwise susceptible fungal cells resume proliferation at supra-MIC concentrations of echinocandins, thereby undermining the efficacy of these frontline antifungals. Despite its clinical significance, the genetic basis of PG remains poorly understood. Here, we systematically dissect the roles of key stress response pathways-Hsp90, PKC, calcineurin, and TOR-in mediating caspofungin (CSP)-induced PG in Candida albicans and uncover a novel genetic mechanism involving segmental aneuploidy. Disruption of these pathways via pharmacological inhibition or targeted gene deletion abolished PG, confirming their essential roles in mediating adaptive stress responses. Whole-genome sequencing of CSP-tolerant isolates revealed a re

SUBMITTER: Wei Y 

PROVIDER: S-EPMC12450983 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature