Clinical and Molecular Advances on the Black Yeast Exophiala dermatitidis
Abstract
1. Introduction
2. Study Selection
3. Ecological Background of Exophiala dermatitidis
3.1. Occurrence in Human Environment
3.2. Natural Habitat, Origin and Hypothetical Transmission Route
4. Clinical and Epidemiological Aspects of Exophiala dermatitidis
4.1. Predisposing Factors
4.1.1. Cystic Fibrosis
4.1.2. CARD9 Deficiency
4.2. Recent Clinical Outcomes
4.2.1. Pulmonary Infections Beyond Cystic Fibrosis
4.2.2. Central Nervous System Infections
4.2.3. Fungemia and Disseminated Infections
4.2.4. Association with Crohn’s Disease
4.2.5. Ocular Infections
4.2.6. Scalp Infections and Hair Loss Involving Exophiala dermatitidis
4.2.7. Exophiala dermatitidis in Polymicrobial Infections
4.2.8. Expanding Clinical Perspectives—Animal Infections
5. Updated Insights into Virulence Factors of Exophiala dermatitidis
5.1. Melanin as a Virulence Factor
5.2. Capsule Formation
5.3. Hydrolytic and Virulence-Associated Enzymes
5.3.1. Catalase
5.3.2. Urease
5.3.3. DNase
5.3.4. Protease
5.3.5. Hemolysins
5.3.6. Other Enzymes and Knowledge Gaps
5.4. Carbon Source Utilization and Metabolic Plasticity
5.5. Other Virulence-Associated Traits
6. Diagnostic and Therapeutic Considerations
6.1. Diagnostic Strategies
6.1.1. Classical Culture-Based Diagnostics
6.1.2. Morphological and Staining Techniques
6.1.3. PCR and ITS Sequencing
6.1.4. STR Genotyping and AFLP
6.1.5. MALDI-TOF Mass Spectrometry
6.1.6. Diagnostic Challenges and Misidentification
6.2. Therapeutic Management
6.2.1. Clinical Approaches
6.2.2. In Vitro Susceptibility Profiles
6.2.3. Successful Treatment Strategies
7. Conclusions and Future Research
Author Contributions
Funding
Conflicts of Interest
Abbreviations
AA | amino acid |
AFLP | amplified fragment length polymorphism |
AIDS | acquired immunodeficiency syndrome |
BCSA | Burkholderia cepacia selective agar |
BYF | black yeast-like fungi |
CARD9 | caspase recruitment domain-containing protein 9 |
CF | cystic fibrosis |
CFTR | cystic fibrosis transmembrane regulator |
CD | Crohn’s disease |
CLABSI | central line-associated bloodstream infections |
CLRs | C-type lectin receptors |
CNS | central nervous system |
COPD | chronic obstructive pulmonary disease |
COVID | coronavirus disease |
CXCL/R | C-X-C motif chemokine ligand/receptor |
D1/D2 | domains 1 and 2 of the large subunit ribosomal RNA gene |
DHN | 1,8-dihydroxynaphthalene |
DIC | differential interference contrast |
ECA | erythritol chloramphenicol agar |
FFPE | formalin-fixed paraffin-embedded |
GABA | γ-aminobutyric acid |
GI | gastrointestinal |
HGA | homogentisic acid |
HIV | human immunodeficiency virus |
ID | identification |
IL | interleukin |
INDEL | insertion-deletion |
ITS | internal transcribed spacer |
L-DOPA | L-3,4-dihydroxyphenylalanine |
KS | keto-synthase |
MALDI-TOF | matrix-assisted laser desorption ionization time-of-flight |
MAPK | mitogen-activated protein kinase |
MEA | malt extract agar |
MIC | minimal inhibitory concentration |
mNGS | metagenomic next-generation sequencing |
MS | mass spectrometry |
Myb-like | myeloblastosis-like |
NET | neutrophil extracellular trap |
NF-κB | nuclear factor kappa-light-chain-enhancer of activated B cells |
NI | not investigated |
PAMP | pathogen-associated molecular pattern |
PCR | polymerase chain reaction |
Pks | polyketide synthase |
PRRs | pattern recognition receptors |
RBC | red blood cells |
ROS | reactive oxygen species |
SDA | Sabouraud dextrose agar |
SGCA | Sabouraud gentamicin chloramphenicol agar |
SH-SY5Y | human-derived neuroblastoma cell line, subclone of SK-N-SH |
SNP | single nucleotide polymorphism |
SOD | superoxide dismutase |
STR | short tandem repeat |
TCA | tricarboxylic acid cycle |
TH17/22 | T helper 17/22 |
TLRs | Toll-like receptors |
TNF-α | tumor necrosis factor α |
YPD | yeast extract-peptone-dextrose |
Appendix A. Extended Data on Exophiala dermatitidis
Appendix A.1. Additional Background Information
Appendix A.2. Macro- and Micromorphology of Exophiala dermatitidis
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Clinical Manifestation | Immunocompetence | Predisposing Factors | Outcome | Refs. |
---|---|---|---|---|
Pulmonary (non-CF) | No | Transplant, chemotherapy | Often fatal | [47,48] |
CNS | Often yes | CARD9 1, East Asia | High mortality | [49,50] |
Fungemia | No | Catheter, malignancy | Poor if delayed | [51,52,53] |
Crohn’s disease | Possibly | Immune dysregulation | Variable | [45,54,55,56] |
Ocular | No | Surgery, steroids | Graft failure | [57,58,59] |
Hair loss/scalp | Possibly | Possibly dysbiosis | Not confirmed | [60] |
Polymicrobial (lung, blood) | Both | Biofilm, devices | Complex | [43,61,62,63,64,65,66,67] |
Melanin Type | Biosynthetic Pathway | Environmental Triggers | Functions | Refs. |
---|---|---|---|---|
DHN–melanin | Polyketide pathway (via Pks1p) | Constitutively produced | Invasion, resistance to ROS, structural reinforcement | [77,78,79] |
L-DOPA–melanin | From L-DOPA via laccase/tyrosinase | Host-like conditions (e.g., CNS) | Possible neurotropism mimicry | [76] |
Pyomelanin | Tyrosine degradation (via HGA) | Oxidative stress | Iron scavenging, stress resistance | [76] |
Enzyme | Function | Detection Frequency | Comments | Refs. |
---|---|---|---|---|
Catalase | Detoxifies H2O2; oxidative stress protection | 100% of strains | Core survival factor; bifunctional catalase/peroxidase also predicted | [84,85,86,87] |
Urease | pH neutralization; evasion of macrophages | Variable (5–100%) | Correlates with ammonia tolerance; possibly host-induced | [85,86,87,88,89] |
DNase | Degrades NETs/DNA traps | Rare (0–2%) in vitro; present in ex vivo RNA-seq | Likely conditionally expressed | [77,86,87,90] |
Protease | Host tissue degradation; immune evasion | Rare in vitro | Serine protease expression upregulated in host context | [77,85,86,91] |
Hemolysin | Iron acquisition via RBC lysis | Variable (0–93%) | Only α-hemolysis reported; strain-dependent | [10,85,92] |
Phospholipase | Membrane degradation | Not detected | No activity observed under current methods | [86,87,93,94] |
Oxidases | ROS metabolism | Not detected | No activity observed under current methods | [95,96,97] |
Esterase | Various (e.g., invasion, ROS defense) | Unknown or unexplored | Identified in other fungi; not studied in E. dermatitidis | [95,96,97] |
SOD | ||||
Hyaluronidase | ||||
Elastase |
Carbon Source | Physiological Context in the Human Host | Refs. |
---|---|---|
Common sugars and derivatives | ||
Glucose | Abundant in blood and tissues; primary carbon source efficiently assimilated. | [50,86,104] |
Fructose | Present in diet and bloodstream at low levels; assimilation likely via sorbitol intermediates. | [10,86,105] |
Sucrose | Dietary disaccharide not naturally present in tissues; transiently available in GI tract. | [10,86,104] |
Inulin | Dietary fructan polysaccharide not digested by humans; fermented by gut microbiota. | [10,104] |
Galactose | Released from mucins and glycoproteins during tissue degradation. | [10,86,104] |
N-acetyl-D-glucosamine | Component of microbial and fungal cell walls present in human niches. | [10,86] |
Polyols and sugar alcohols | ||
Sorbitol | Accumulates in diabetic tissues as polyol pathway intermediate. | [10,86] |
Glycerol | Lipid metabolite, available in tissues and blood. | [10,86,104] |
Organic acids and metabolites | ||
2-keto-D-gluconate | Intermediate metabolite in different metabolic pathways. | [86,104] |
Succinate | Common TCA cycle intermediate found in host cells and tissues. | [10,104] |
Glucuronate | Involved in detoxification pathways; present in extracellular matrix. | [10,104] |
Lactate | Present in inflamed tissues and vaginal environments. | [104] |
Neurotransmitters and AAs | ||
GABA | Major neurotransmitter in CNS. | [50] |
Dopamine | Neurotransmitter and melanin precursor. | [10,50] |
Serotonin | CNS and GI tract neurotransmitter. | [10] |
Norepinephrine/epinephrine | Neurotransmitters and hormones, present in blood and various tissues. | [10] |
Tryptophan | Aromatic amino acid with catabolites linked to virulence. | [10,106] |
Glutamate | Major excitatory neurotransmitter in the CNS and a key amino acid in tissue metabolism. | [10,50] |
Aromatic and environmental compounds | ||
Phenol | Environmental and host-derived toxin. | [10] |
Catechol | Oxidized metabolite and melanin precursor. | [10] |
Method | Time | Specificity | Advantages | Limitations | Refs. |
---|---|---|---|---|---|
Culture | 2–7 days | Low–Moderate | Widely available, supports further testing | Slow growth, risk of contamination | [2,57,59] |
Microscopy | <1 day | Low | Simple, quick | Low discriminatory power | [57] |
ITS Sequencing | 1–3 days | High | Species-level ID, phylogenetic value | Requires sequencing facility | [48,55,107,108,109] |
STR Genotyping | 2–3 days | High | Strain typing, outbreak tracing | Requires multiplex PCR and interpretation | [110] |
AFLP | 2–4 days | High | High genotypic resolution | Technically demanding | [111] |
MALDI-TOF MS | <1 day | Moderate–High | Rapid, cost-effective | Database-dependent, variable reliability | [58,62,112,113] |
mNGS | 1–3 days | High | Unbiased detection of rare/novel pathogens; works on FFPE | Expensive; requires bioinformatics infrastructure | [114] |
Agent | MIC Range (µg/L) | Median In Vitro Activity | Biofilm Efficacy | Clinical Notes | Refs. |
---|---|---|---|---|---|
Voriconazole | 0.002–8 | High | Reduced | First-line therapy in many case reports. | [26,61,87,115,118,119] |
Fluconazole | 0.5–256 | Poor | Poor | Largely ineffective. | [10,26,61,87,115,118,119] |
Itraconazole | 0.03–2 | High | Reduced | Effective in CF and localized infections. | [10,61,64,87,115,118,119] |
Posaconazole | 0.002–0.5 | High | Reduced | Alternative to voriconazole. | [61,87,115,118,119] |
Miconazole | 0.12–5 | Moderate | NI | Rarely used. | [61,118] |
Amphotericin B | 0.064–2 | Moderate | Reduced | Used in severe and disseminated cases. | [26,61,87,115,118] |
5-fluorocytosine | 1–128 | Poor | Poor | Largely ineffective. | [61,87,115] |
Micafungin | 0.125–16 | Poor | Poor | Echinocandin class; limited activity. | [115,118] |
Anidulafungin | 0.008–32 | Poor | Poor | Similar limitations as micafungin. | [26,87,115,119] |
Caspofungin | 0.008–32 | Poor | Poor | Not recommended due to resistance. | [87,115,118,119] |
Terbinafine | 0.06–0.13 | High | High | Rarely used. | [10,115,118] |
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Suchodolski, J.; Parol, M.; Pawlak, K.; Piecuch, A.; Ogórek, R. Clinical and Molecular Advances on the Black Yeast Exophiala dermatitidis. Int. J. Mol. Sci. 2025, 26, 6804. https://doi.org/10.3390/ijms26146804
Suchodolski J, Parol M, Pawlak K, Piecuch A, Ogórek R. Clinical and Molecular Advances on the Black Yeast Exophiala dermatitidis. International Journal of Molecular Sciences. 2025; 26(14):6804. https://doi.org/10.3390/ijms26146804
Chicago/Turabian StyleSuchodolski, Jakub, Mateusz Parol, Karolina Pawlak, Agata Piecuch, and Rafał Ogórek. 2025. "Clinical and Molecular Advances on the Black Yeast Exophiala dermatitidis" International Journal of Molecular Sciences 26, no. 14: 6804. https://doi.org/10.3390/ijms26146804
APA StyleSuchodolski, J., Parol, M., Pawlak, K., Piecuch, A., & Ogórek, R. (2025). Clinical and Molecular Advances on the Black Yeast Exophiala dermatitidis. International Journal of Molecular Sciences, 26(14), 6804. https://doi.org/10.3390/ijms26146804