A Calcineurin Inhibitor as an Enhancer of Candida Susceptibility to Anidulafungin

TL;DR

This study shows that combining tacrolimus with anidulafungin can enhance antifungal effects, especially against drug-resistant Candida species like C. auris.

Contribution

The study demonstrates that tacrolimus, a calcineurin inhibitor, synergistically enhances anidulafungin's activity against Candida isolates, including drug-resistant strains.

Findings

Tacrolimus reduced anidulafungin MIC values in 90% of Candida isolates.

Synergy was particularly strong against multidrug-resistant C. auris, showing 100% synergy.

Time-kill assays confirmed enhanced antifungal activity against C. parapsilosis with FKS1 mutations.

Abstract

The increase in invasive
candidiasis caused by emerging Candida species presents
a significant medical challenge
due to their resistance to conventional antifungal treatments. Exploring
novel therapeutic strategies, such as drug repurposing, is therefore
essential. Tacrolimus, an immunosuppressive calcineurin inhibitor,
shows potential antifungal effects. This study investigated the in
vitro effect of combining tacrolimus and echinocandin anidulafungin
using the checkerboard method against 60 clinical Candida isolates, including Candida albicans, Candida auris, Candida
glabrata, and Candida parapsilosis. Time-kill assays against C. parapsilosis clinical isolates with FKS1 gene mutations were
conducted. Checkerboard data revealed that tacrolimus reduced anidulafungin
MIC values: a synergistic activity was observed against 90% of the
isolates studied, with a particularly notable effect against multidrug-resistant C. auris, showing 100% synergy. Positive outcomes
were corroborated by time-kill assays. Hence, the addition of tacrolimus
may enhance susceptibility to anidulafungin, as suggested by checkerboard
and time-kill assays conducted against C. parapsilosis, including isolates harboring mutations in FKS1. These promising findings are a starting point for future studies
on the antifungal properties of tacrolimus and related compounds.

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