The Neurotropic Black Yeast Exophiala dermatitidis Induces Neurocytotoxicity in Neuroblastoma Cells and Progressive Cell Death

Abstract

The neurotropic and extremophilic black yeast Exophiala dermatitidis (Herpotrichellaceae) inhabits diverse indoor environments, in particular bathrooms, steam baths, and dishwashers. Here, we show that the selected strain, EXF-10123, is polymorphic, can grow at 37 °C, is able to assimilate aromatic hydrocarbons (toluene, mineral oil, n-hexadecane), and shows abundant growth with selected neurotransmitters (acetylcholine, gamma-aminobutyric acid, glycine, glutamate, and dopamine) as sole carbon sources. We have for the first time demonstrated the effect of E. dermatitidis on neuroblastoma cell model SH-SY5Y. Aqueous and organic extracts of E. dermatitidis biomass reduced SH-SY5Y viability by 51% and 37%, respectively. Melanized extracellular vesicles (EVs) prepared from this strain reduced viability of the SH-SY5Y to 21%, while non-melanized EVs were considerably less neurotoxic (79% viability). We also demonstrated direct interactions of E. dermatitidis with SH-SY5Y by scanning electron and confocal fluorescence microscopy. The observed invasion and penetration of neuroblastoma cells by E. dermatitidis hyphae presumably causes the degradation of most neuroblastoma cells in only three days. This may represent a so far unknown indirect or direct cause for the development of some neurodegenerative diseases such as Alzheimer’s.

Microorganisms populating the water-related indoor biome

“…The main traits that define fungal opportunism and colonisation of stressful indoor environments are thermotolerance in combination with osmotolerance/osmophily, and oligotrophism, together with siderophore production at 37 °C, production of different hydrolytic enzymes, urease activity, use of different hydrocarbons as sole carbon source, tolerance to oxidative stress, melanisation and biofilm production (de Hoog et al 2005 ; Gostinčar et al 2018 ; Lavrin et al 2020 ). While some of these traits are known for Candida spp., Fusarium oxysporum (FOSC) and F. solani complexes (FSSC), all of these are characteristic for the black yeast E. dermatitidis , dominant fungus in dishwashers around the world (Zalar et al 2011 ; Lavrin et al 2020 ), and A. melanogenum prevailing in tap water (Novak Babič et al 2016b , 2017a ).…”

“…Many polyextremotolerant fungi are additionally protected by melanisation of the cell walls. Melanin shields fungal cells by acting as a scavenger of reactive oxygen species, protecting them against different types of abiotic stress (Slepecky and Starmer 2009 ; Gostinčar et al 2012 ; Kogej et al 2007 ; Kejžar et al 2013 ) and increases their resistance to lysis, phagocytosis and to clinically used antifungal agents (van Baarlen et al 2007 ; Feng et al 2001 ; Nosanchuk et al 2015 ; Schnitzler et al 1999 ; Lavrin et al 2020 ).…”

“…Some polyextremotolerant fungi are able to assimilate monoaromatic hydrocarbons as carbon sources, and these species are frequently encountered both in outdoor hydrocarbon-polluted environments and indoors in plastic-rich niches (Döğen et al 2013a , b ; Seyedmousavi et al 2011 ; Zhao et al 2010 ; Isola et al 2013 ; Chandran and Das 2012 ). A physiological connection between hydrocarbon assimilation and neural infection was suggested for certain polyextremotolerant black yeasts (Prenafeta-Boldu et al 2006 ; Lavrin et al 2020 ).…”

“…the ability to thrive at 37 °C and above (Robert and Casadevall 2009 ; Chandran and Das 2012 ; Gostinčar et al 2018 ). This generally rare ability among fungi might become more frequent in the future, due to increased urbanisation and increased occurrence of high-temperature domestic environments and thermal adaptations of fungi on a global scale (Gostinčar et al 2011 ; Lavrin et al 2020 ).…”

“…Many species of black fungi are now increasingly being recognised as medical problems (Silveira and Nucci 2001 ; Chowdhary et al 2014 ; Lavrin et al 2020 ). Greater numbers of susceptible hosts, improved diagnostics and recognition of water-related indoor microbiomes and changes of our lifestyle have all been proposed as reasons for this trend (Casadevall et al 2011 ; Gostinčar et al 2011 , 2015 ).…”