Computation-Driven Analysis of Model Polyextremo- tolerant Fungus Exophiala dermatitidis: Defensive Pigment Metabolic Costs and Human Applications

Authors

Wheaton L. Schroeder, University of Nebraska – LincolnFollow
Steven D. Harris, University of Manitoba, WinnipegFollow
Rajib Saha, National University of SingaporeFollow

Date of this Version

2020

Document Type

Article

Citation

iScience 23, https://doi.org/10.1016/j.isci. 2020.100980

Comments

2020 The Author(s)

Abstract

Extremophiles are organisms that can live in extreme conditions of temperature, acidity, alkalinity, or salinity. Studying these organisms not only expands our knowledge on the diversity of life but can also provide significant insights into how organisms adapt to stress, particularly metabolic and regulatory responses. Exophiala dermatitidis (hereafter, Exophiala or E. dermatitidis, also known as Wangiella derma- titidis), a highly melanized black fungus and perhaps best known for its H. sapiens (hereafter, human) path- ogenic properties (Paolo et al., 2006; Poyntner et al., 2016; Sudhadham et al., 2008), is a potential model extremophile system owing to its small genome of 26.4 Mb (Exophiala dermatitidis NIH/UT8656 Genome, 2011) and its demonstrated extremotolerance with respect to temperature (heat and cold) (Paolo et al., 2006; Sudhadham et al., 2008), acidic pH (Sudhadham et al., 2008; Chen et al., 2014), light (Chen et al., 2014; Nosanchuk and Casadevall, 2006; Geis and Szaniszlo, 1984), radiation (Chen et al., 2014; Nosanchuk and Casadevall, 2006; Geis and Szaniszlo, 1984), oxidative stress (Chen et al., 2014; Geis and Szaniszlo, 1984), and likely tolerance to toxic heavy metals (Nosanchuk and Casadevall, 2006), harmful aromatic com- pounds (Moreno et al., 2018), various toxins (Moreno et al., 2018), antimicrobial compounds (Nosanchuk and Casadevall, 2006), and other stressors (nutrient, osmotic, and mechanical) (Moreno et al., 2018). The ability of Exophiala to adapt to most of these conditions seemingly results from two classes of defensive pigments: melanins, a class of pigments consisting of six-carbon ring monomers, and carotenoids, a class of polyisoprenoid pigments. Exophiala can produce three different types of melanin: (1) 1,8-dihydroxy- naphthalene melanin (hereafter, DHN-melanin), also called naphthalene melanin, (2) DOPA-melanin, also known as eumelanin (Ito and Wakamatsu, 2011), and (3) pyomelanin. Among these, DHN-melanin and pyomelanin are generally produced by fungi (Solano, 2014) including Exophiala, whereas eumelanin is produced by both fungi and animals, including humans (Ito and Wakamatsu, 2011; Solano, 2014). The combination of its small genome (Exophiala dermatitidis NIH/UT8656 Genome, 2011), its ability to be cultured as yeast cells (Chen et al., 2014; Ohkusu et al., 1999), and production of eumelanin (Ito and Waka- matsu, 2011) makes Exophiala a potential model organism for human melanocytes, the cells in humans that produce melanins. Melanocytes are specialized cells in humans that are found primarily in the skin, which produce pheomelanin and eumelanin in specialized subcellular organelles called melanosomes.