Cyclophilin BcCyp2 Regulates Infection-Related Development to Facilitate Virulence of the Gray Mold Fungus .

Cyclophilin (Cyp) and Ca/calcineurin proteins are cellular components related to fungal morphogenesis and virulence; however, their roles in mediating the pathogenesis of , the causative agent of gray mold on over 1000 plant species, remain largely unexplored. Here, we show that disruption of cyclophilin gene did not impair the pathogen mycelial growth, osmotic and oxidative stress adaptation as well as cell wall integrity, but delayed conidial germination and germling development, altered conidial and sclerotial morphology, reduced infection cushion (IC) formation, sclerotial production and virulence. Exogenous cyclic adenosine monophosphate (cAMP) rescued the deficiency of IC formation of the ∆ mutants, and exogenous cyclosporine A (CsA), an inhibitor targeting cyclophilins, altered hyphal morphology and prevented host-cell penetration in the harboring strains. Moreover, calcineurin-dependent (CND) genes are differentially expressed in strains losing in the presence of CsA, suggesting that BcCyp2 functions in the upstream of cAMP- and Ca/calcineurin-dependent signaling pathways. Interestingly, during IC formation, expression of is downregulated in a mutant losing , a gene encoding histone 3 lysine 4 (H3K4) demethylase that regulates fungal development and pathogenesis, in , implying that BcCyp2 functions under the control of BcJar1. Collectively, our findings provide new insights into cyclophilins mediating the pathogenesis of and potential targets for drug intervention for fungal diseases.