Genetic and pharmacologic inhibition of calcineurin reduces biofilm formation by the pathogenic fungus Trichosporon asahii in an in vivo silkworm infection model

TL;DR

This study shows that calcineurin is important for biofilm formation by the fungus Trichosporon asahii in a living host, but not in lab conditions.

Contribution

The study reveals calcineurin's role in T. asahii biofilm formation specifically in a host environment, not observed in vitro.

Findings

Calcineurin gene-deficient mutants formed normal biofilms in vitro but less in vivo.

The calcineurin inhibitor tacrolimus suppressed biofilm formation in vivo but not in vitro.

Calcineurin is crucial for T. asahii biofilm formation under host environmental conditions.

Abstract

Trichosporon asahii is a dimorphic pathogenic fungus that causes catheter-related bloodstream infection in immunocompromised patients with neutropenia. Biofilm formation by T. asahii on the surfaces of medical devices such as catheters is influenced by various host environmental factors. Calcineurin, a protein phosphatase composed of the catalytic subunit Cna1 and the regulatory subunit Cnb1, regulates multiple stress responses and virulence of T. asahii. The role of calcineurin in biofilm formation under host-derived conditions, however, remains unclear. Here, we demonstrated that calcineurin is essential for biofilm formation in vivo by T. asahii. While the cna1 gene- and the cnb1 gene-deficient mutants formed biofilms comparable to those of the parent strain in vitro, it produced significantly less biofilm than the parent strain in the in vivo silkworm infection model. Similarly, tacrolimus, a calcineurin inhibitor, did not inhibit biofilm formation by T. asahii in vitro but markedly suppressed biofilm formation in vivo. Together, these findings suggest that calcineurin plays a crucial role in biofilm formation by T. asahii under host environmental conditions.

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