P4-ATPase BbCrpa2 detoxifies cyclosporine a via AP2-clathrin-dependent endocytic pathway in Beauveria bassiana.

BbCrpa2, a plasma membrane P4-ATPase in Beauveria bassiana, is a key determinant of CsA resistance by mediating its endocytic internalization with 100% dependence on AP2-clathrin pathways.

• Why it matters: Understanding fungal tolerance to CsA is important because CsA exerts potent intracellular toxicity, and the mechanisms of fungal resistance are largely unknown, hindering potential control strategies.
• What they did: The study identified BbCrpa2 through genetic and functional analyses, showing it captures CsA at the cell surface and internalizes it via AP2-clathrin-dependent endocytosis, acting independently and additively with BbCrpa.
• The result: Findings reveal a multi-tiered defense involving spatially distinct P4-ATPases that coordinate vesicular CsA transport, enabling fungal tolerance to toxic secondary metabolites.