Calcineurin-responsive zinc finger 1 (Crz1) contributes to stress tolerance and virulence in the pathogenic fungus <i>Trichosporon asahii</i>

The pathogenic fungus <i>Trichosporon asahii</i> causes severe invasive fungal infections in immunocompromised patients with neutropenia. In <i>Cryptococcus neoformans</i>, calcineurin-responsive zinc finger 1 (Crz1) functions as a transcription factor downstream of the calcineurin signaling pathway and regulates the expression of genes involved in stress resistance and virulence. In <i>T. asahii</i>, Cna1 and Cnb1, which are key components of the calcineurin pathway, contribute to various stress responses and virulence. The role of Crz1 in stress tolerance and virulence in <i>T. asahii</i>, however, has remained unclear. Here, we demonstrate that a <i>crz1</i> gene-deficient <i>T. asahii</i> mutant exhibited increased sensitivity to cell wall and endoplasmic reticulum stress. The <i>crz1</i> gene-deficient mutant was sensitive to Congo red and tunicamycin but not to dithiothreitol or sodium dodecyl sulfate. Moreover, the virulence of the <i>crz1</i> gene-deficient mutant in the silkworm infection model was reduced. These phenotypes of the <i>crz1</i> gene-deficient mutant were restored by reintroducing the <i>crz1</i> gene, confirming the association between Crz1 and these phenotypes. The half-maximal lethal dose of the <i>cnb1</i> gene-deficient <i>T. asahii</i> mutant was higher than that of the <i>crz1</i> gene-deficient mutant. These results suggest that Crz1 mediates the stress responses and virulence of <i>T. asahii</i>. The involvement of Crz1 in the virulence of <i>T. asahii</i> is small, however, compared with that of the calcineurin.