Production of Fusaric Acid by Fusarium spp. in Pure Culture and in Solid Medium Co-Cultures.

Nadine Bohni,Valérie Hofstetter,Bart Buyck,Olivier Schumpp,Jean-Luc Wolfender,Katia Gindro,Michel Monod,Samuel Bertrand

doi:10.3390/molecules21030370

Abstract

The ability of fungi isolated from nails of patients suffering from onychomycosis to induce de novo production of bioactive compounds in co-culture was examined. Comparison between the metabolite profiles produced by Sarocladium strictum, by Fusarium oxysporum, and by these two species in co-culture revealed de novo induction of fusaric acid based on HRMS. Structure confirmation of this toxin, using sensitive microflow NMR, required only three 9-cm Petri dishes of fungal culture. A targeted metabolomics study based on UHPLC-HRMS confirmed that the production of fusaric acid was strain-dependent. Furthermore, the detected toxin levels suggested that onychomycosis-associated fungal strains of the F. oxysporum and F. fujikuroi species complexes are much more frequently producing fusaric acid, and in higher amount, than strains of the F. solani species complex. Fusarium strains producing no significant amounts of this compound in pure culture, were shown to de novo produce that compound when grown in co-culture. The role of fusaric acid in fungal virulence and defense is discussed.

Highlights

Onychomycosis is a nail infection caused by systematically diverse fungi, most often by dermatophytes of the genus Trichophyton or, in the case of patients suffering from chronic mucocutaneous candidiasis, by species of Candida [1]
Onychomycosis-derived fungi were phylogenetically identified using five loci and several pairs of these fungi were cultured on Petri dishes and screened for morphological changes in fungal growth with the aim of finding de novo induced compounds
Compound induction was monitored by UHPLC-TOFMS metabolite profiling

Summary

Introduction

Onychomycosis is a nail infection caused by systematically diverse fungi, most often by dermatophytes of the genus Trichophyton or, in the case of patients suffering from chronic mucocutaneous candidiasis, by species of Candida [1]. As fungi and bacteria are ubiquitous, it seems reasonable to assume that several species of fungi can inhabit a single human nail and compete to occupy this particular niche by producing secondary metabolites for defense or to access nutrients. Fungi produce a high diversity of secondary compounds and their induction is often accompanied by changes in the morphotypes of the involved species (reproduction cycles, growth inhibition or stimulation) [11]. The combined growth of onychomycosis-derived human pathogenic fungi together in a co-culture experiment mimics the mycobiome of onychomycosis-affected nails and might stimulate the production of antifungal compounds involved in competitive interactions. This may lead to the discovery of novel compounds with potential use in onychomycosis treatment

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