Exophiala dermatitidis: Key issues of an opportunistic fungal pathogen

Figures & data

Figure 1. Prevalence of E. dermatitidis caused infections in immunocompetent (red = 9 cases) and immunodeficient (blue, 9 cases) patients as reported in case reports since 2007.

Figure 2. Number of cases of E. dermatitidis infections reported in the literature from 1960 to May 2018. Data until 1999 were retrieved from Taj-Aldeen et al. [12]. Latest reports were recorded by carefully scrutinized for case reports.

Table 1. Summary of E. dermatitidis caused infections case reports since 2007.

Age (gender)	Underlying medical condition	Immunodeficiency status	Possible route of infection	Geographical region (Back ground)	Clinical manifestation	Year	Ref
81 (f)	Localized bronchiectasis	Competent	Unknown	Japan	Bronchial infection	2007	[48]
24 (f)	Tinea versicolor for skin lesion	Competent	Traumatic inoculation	Turkey	Sclerosing cholangitis	2009	[49]
3 (m)	Non	Competent	Hematogenous	China	CNS infection	2009	[50]
8 (m)	Non	Competent	Unknown	Turkey	Systemic phaeohyphomycosis	2009	[51]
65 (m)	Hypertension, Multiple myeloma	Competent	Unknown	Japan	Lung nodule	2012	[22]
40 (f)	Kidney transplant	Compromised	Possibility of primary subcutaneous infection	India	Endocarditis	2013	[52]
60 (m)	Chronic herpes zoster keratitis	Unknown	Unknown	USA	Endophthalmitis	2014	[53]
21 (m)	Left ear abscesses	Competent	Direct extension to the brain	India	CNS infection	2014	[41]
57 (m)	Graft-versus-host disease, Mantle cell lymphoma, Hematopoietic stem cell transplant	Compromised	Unknown	USA	Fungemia	2014	[40]
8 (f)	Card9 deficiency	Compromised	Unknown	France (Nigeria)	Liver and brain infection	2015	[38]
78 (m)	Non	Competent	Unknown	China	Ulcer on right forearm	2016	[42]
8 (m)	Allogenic stem cell transplantation, acute myeloid leukemia	Compromised	Unknown	Slovakia	Systemic phaeohyphomycosis	2017	[43]
48 (f)	Lepromatous leprosy	Compromised	Unknown	Brazil	Subcutaneous phaeohyphomycosis	2017	[44]
64 (m)	Kidney transplant	Compromised	Unknown	Brazil	Pneumonia	2017	[39]
14 (f)	Ewing’s sarcoma	Compromised	Unknown	Brazil	Fungemia, disseminated infection	2017	[39]
44 (f)	Hip fracture	Unknown	Unknown	Brazil	Fungemia, disseminated infection	2017	[39]
3 (m)	Soft tissue sarcoma	Compromised	Unknown	Brazil	Fungemia, disseminated infection	2017	[39]
15 (f)	Non	Competent	Unknown	India	Phaeohyphomycosis	2017	[45]
28 (f)	Unknown	Compromised	Inoculation through skin	Canada (India)	Osteomyelitis, septic arthritis	2018	[46]
59 (m)	Uneventful cataract surgery	Competent	Unknown	India	Endolphtalmitis	2018	[47]

Figure 3. Light microscopy E. dermatitidis (CBS 149.90) colonies on malt extract agar after 48 h of incubation at 35°C. Scale bar equals 200 µm (Credits: M. Olsowski).

Figure 4. Survival curve of Galleria mellonella infected with E. dermatitidis Environmental isolates (E), CF patients isolates (CF) and Isolates from Asian, immunocompetent patients (PA). Depicted values are means of nine tested strains. Each strain was tested in triplicate. Taken from: Olsowski et al., 2018 [91].

Table 2. Virulence factors of Exophiala dermatitidis.

Virulence factor	Reference
Pigmentation	Dixon et al., 1987 [93]; Feng et al., 2001 [94]; Langfelder et al., 2003 [95]
Polymorphism	De Hoog & Guarro, 1995 [18]; Boral et al., 2018 [85],
Hydrophobicity	De Hoog, 1993 [97]
Biofilm formation and adhesion	Seneviratne et al., 2015 [131]; Sav et al., 2016 [98], Kirchhoff et al., 2017 [130],
Urease production	Sav 2016 [98]
Catalase production	Sav 2016 [98]
Proteinase (strain-dependent)	Sav 2016 [98]
DNase (strain-dependent)	Sav 2016 [98]
Encapsulation	Yurlova & De Hoog, 2002 [2]; Boral et al., 2018 [85]
Chitin synthases	Wang et al., 2001 [101]; Wang & Szaniszlo, 2002 [100]; Abramczyk & Szaniszlo, 2009 [99]
Assimilation of aromatic hydrocarbons	Prenafeta-Boldú et al., 2006 [55]; Isola et al., 2013 [103]
Secondary metabolite production	De Hoog, 1993 [97]; Kindler et al., 2010 [102]

Figure 5. E. dermatitidis (CBS 116372) biofilm after 48 h of incubation at 35°C, fixation in methanol and staining by acridine orange in a confocal laser scan microscopy. Taken from: Kirchhoff et al., 2017 [130].

Table 3. MIC ranges of several drugs (No. of isolates) against E. dermatitidis isolates from various origins. AMB = amphotericin B, ANI = anidulafungin, CAS = caspofungin, COL = colistin, FLC = fluconazole, ISC = isavuconazole, ITC = itraconazole, MICA = micafungin, POS = posaconazole, TBF = terbinafine, VRC = voriconazole, 5-FC = fluorcytosine.

Strain origin	MIC ranges in μg/mL (No. of isolates) for													References
	AMB	5-FC	FLC	ISC	ITC	POS	VRC	ANI	CAS	MICA	TBF	COL	FK506
Clinical	0.094–4 (172)	0.012-≥ 100 (70)	0.25-≥100 (58)	0.031–1 (66)	0.016–8 (182)	<0.002–0.25 (162)	0.004–16 (188)	0.25 -≥32 (3)	0.008- ≥32 (4)	8->32 (6)	≤0.01 (11)	64-≥512 (3)	>16 (16)	[22,30, 43, 47,123, 130, 132–135, 138, 140]
Environ.	0.12–4 (112)	0.12-≥64 (43)	2->64 (109)	0.125–1 (15)	≤0.015–2 (109)	0.016–2 (66)	0.015–2 (112)	0.25–8 (1)	2–16 (1)	-	-	≤0.003–4 (97)	-	[134–137]

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