Exophiala Xenobiotica Research Articles

Metabologenomics-Inspired Discovery and Combinatorial Biosynthesis-Based Diversification of Fungal O-Glycosylated Depsides.

Through metabologenomics mining, we prioritized Exophiala xenobiotica SDU 039, a deep-sea sediment-derived fungus producing O-glycosylated depsides (1-9), including seven new species with varying aliphatic chains. Heterologous expression validated the exo gene cluster, and in vitro enzyme assays elucidated the function of glycosyltransferase ExoC. The chemical diversity of O-glycosylated depsides is expanded by combinatorial biosynthesis using homologues depside biosynthetic genes and in vitro transformation with ExoC and different sugars as substrate.

Simultaneous distinct cutaneous fungal infections with chromoblastomycosis due to Exophiala xenobiotica and hyalohyphomycosis due to Scedosporium apiospermum in a patient with severe cellular immunodeficiency.

Deep-seated dermatomycosis is a rare disease that is often caused by trauma and/or systemic immunodeficiency. We describe a case of chromoblastomycosis complicated by hyalohyphomycosis that occurred simultaneously at different sites. A 92-year-old Japanese man who had been taking oral prednisolone for an IgG4-related respiratory disease visited our clinic. He developed brownish plaques with grayish-white scales with pseudo-carcinomatous hyperplasia and numerous brownish muriform cells developing in the dermis of his right hand, and multiple painful abscesses with pustules and papules and numerous hyphae within and around the histiocytes in the dermis of his right lower leg. Upon skin tissue culture and DNA sequencing, Exophiala xenobiotica and Scedosporium apiospermum were detected separately. He had severe cellular immunodeficiency indicated by low levels in the phytohemagglutinin (PHA)-stimulated lymphocyte transformation test (LTT) and serum interferon-gamma (IFN-γ), although his humoral immunity was normal. The patient died of bacterial pneumonia, despite antifungal drug treatment for 2 months. IFN-γ producing type 1 T helper (Th1) cells play an important role in the defense against fungal infections, however, corticosteroids specifically suppress Th1 cell responses and promote the induction of fungal infection. Measurement of PHA-stimulated LTT and serum IFN-γ may be useful in determining the severity and prognosis of deep-seated dermatomycosis in patients undergoing corticosteroid treatment.

Clinical Evaluation of VITEK MS PRIME with PICKME Pen for Bacteria and Yeasts, and RUO Database for Filamentous Fungi.

The VITEK MS PRIME (bioMérieux, Marcy-l'Étoile, France), a newly developed matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) system, alongside the VITEK PICKME pen (PICKME), offers easy sample preparation for bacteria and yeasts. The VITEK MS PRIME also offers two software platforms for filamentous fungi: the IVD database and the RUO database. Our study evaluated its identification agreement on 320 clinical isolates of bacteria and yeasts, comparing PICKME and traditional wooden toothpick sampling techniques against MicroIDSys Elite (ASTA) results. Additionally, we assessed the IVD (v3.2) and SARAMIS (v4.16) RUO databases on 289 filamentous fungi against molecular sequencing. The concordance rates for species-level identification of bacteria and yeasts were about 89.4% (286/320) between the PICKME and wooden toothpick, and about 83.4-85.3% between the VITEK MS PRIME and ASTA MicroIDSys Elite. Retesting with PICKME improved concordance to 91.9%. For filamentous fungi, species-level identification reached 71.3% with the IVD database and 85.8% with RUO, which significantly enhanced basidiomycetes' identification from 35.3% to 100%. Some strains in the IVD database, like Aspergillus versicolor, Exophiala xenobiotica, and Nannizzia gypsea, failed to be identified. The VITEK MS PRIME with PICKME offers reliable and efficient microorganism identification. For filamentous fungi, combined use of the RUO database can be beneficial, especially for basidiomycetes.

The First Case of Phaeohyphomycosis Caused by Exophiala xenobiotica in an Immunocompetent Patient in Korea

Phaeohyphomycosis is a rare fungal infection caused by dematiaceous fungi commonly associated with immunocompromised patients. Exophiala (E.) species are linked to phaeohyphomycosis, and in Korea, E. dermatitidis, E. jeanselmei, and E. salmonis were previously isolated from affected patients. Here, we describe a unique instance of phaeohyphomycosis in an immunocompetent patient attributed to E. xenobiotica. A 75-year-old female presented with an asymptomatic erythematous crusted subcutaneous nodule on the dorsum of her left-hand. Her past medical history was negative for immunosuppression or trauma to the affected area. Histopathological examination revealed suppurative granulomatous infiltration, with septate hyphae and spores detected by periodic acid-Schiff staining in the dermis. A fungal culture made from a tissue sample revealed E. xenobiotica, with subsequent confirmation through phylogenetic analyses of the internal transcribed spacer (ITS) and large subunit regions (LSU) of ribosomal ribonucleic acid (rRNA). The patient was diagnosed with phaeohyphomycosis and underwent a 3-week course of terbinafine, followed by 7 weeks of fluconazole. These treatments significantly improved the lesion. To our knowledge, this is the first reported case of phaeohyphomycosis caused by E. xenobiotica in Korea.

Draft genome sequence of a black yeast fungus Exophiala xenobiotica isolated from La Brea Tar Pits.

A 30.28 Mb draft genome sequence was assembled and annotated for the melanized ascomycetous fungus Exophiala xenobiotica NRRL_64630 (Pezizomycotina; Chaetothyriales) isolated from La Brea Tar Pits, Los Angeles, California. Species identification was made by phylogenetic assessment of the Internal Transcribed Spacer. This is the first isolated fungal species from this historic space.

Characteristics and Correlations of the Oral and Gut Fungal Microbiome with Hypertension.

The mycobiome is an essential constituent of the human microbiome and is associated with various diseases. However, the role of oral and gut fungi in hypertension (HTN) remains largely unexplored. In this study, saliva, subgingival plaques, and feces were collected from 36 participants with HTN and 24 healthy controls for metagenomic sequencing. The obtained sequences were analyzed using the Kraken2 taxonomic annotation pipeline to assess fungal composition and diversity. Correlations between oral and gut fungi and clinic parameters, between fungi within the same sample types, and between different sample types were identified by Spearman's correlation analysis. Overall, the subgingival fungal microbiome had substantially higher alpha diversity than the salivary and fecal fungal microbiomes. The fungal microbiomes of the three sample types displayed distinct beta diversity from each other. Oral fungi but not gut fungi in HTN had beta diversity significantly different from that of controls. Among the fungi shared in the oral cavity and gut, Exophiala was the genus with the most notable changes. Exophiala spinifera was the most abundant salivary species in HTN. Some fungal species directly correlated with blood pressure, including gut Exophiala xenobiotica and Exophiala mesophila. The markedly impaired ecological cocorrelation networks of oral and gut fungi in HTN suggested compromised association among fungal species. Most fungi were shared in the oral cavity and gut, and their correlations suggested the potential interplays between oral and gut fungi. In conclusion, the oral cavity and intestine have unique fungal ecological environments. The fungal enrichment and ecology in HTN, the correlations between oral and gut fungi, and the associations between oral and gut fungi and clinical parameters suggest an important role that the fungal microbiome may play in HTN. IMPORTANCE Our study fills the gap in human studies investigating the oral and gut fungal microbiota in association with blood pressure. It characterizes the diversity and composition of the oral and gut fungal microbiome in human subjects, elucidates the dysbiosis of fungal ecology in a hypertensive population, and establishes oral-gut fungal correlations and fungus-clinical parameter correlations. Targeting fungi in the oral cavity and/or gut may provide novel strategies for the prevention and treatment of hypertension.

Exogenous Fungal Endophthalmitis by Exophiala xenobiotica Infection after Cataract Surgery

Purpose: To report a case of fungal endophthalmitis secondary to <i>Exophiala xenobiotica</i> after cataract surgery.Case summary: A 79-year-old male presented with decreased visual acuity in the left eye 8 months after cataract surgery. He was diagnosed with uveitis and received subtenon triamcinolone injection, which has a temporary effect. Three months after the injection, his visual acuity had decreased, such that best-corrected visual acuity (BCVA) of the left eye was hand motion. Anterior chamber cells with hypopyon and severe vitritis with vitreous haze were observed in the left eye. We considered the possibility of endophthalmitis after cataract surgery, and repetitive anterior chamber irrigation with culture was conducted to identify pathogens. Systemic and intravitreal antifungal agents were injected after the isolation of <i>Exophiala xenobiotica</i>. However, there was no improvement of the endophthalmitis, and he underwent pars plana vitrectomy. Although inflammatory symptoms disappeared after surgery, black lesions in the corneal incision site were identified 3 months postoperatively. Ultimately, surgical debridement and anterior chamber injections of antifungal agents were performed for recurring endophthalmitis. After the surgery, there was no inflammation of the anterior chamber or vitreous cavity. The BCVA of the left eye improved to 0.5.Conclusions: Ophthalmologists should consider the possibility of fungal endophthalmitis in patients who suffer from uveitis-like symptoms after cataract surgery.

Hydrocarbon-Contaminated Sites: Is There Something More Than Exophiala xenobiotica? New Insights into Black Fungal Diversity Using the Long Cold Incubation Method.

Human-made hydrocarbon-rich environments are important reservoirs of microorganisms with specific degrading abilities and pathogenic potential. In particular, black fungi are of great interest, but their presence in the environment is frequently underestimated because they are difficult to isolate. In the frame of a biodiversity study from fuel-contaminated sites involving 30 diesel car tanks and 112 fuel pump dispensers (52 diesel and 60 gasoline, respectively), a total of 181 black fungal strains were isolated. The long cold incubation (LCI) of water-suspended samples, followed by plating on Dichloran Rose Bengal Chloramphenicol Agar (DRBC), gave isolation yields up to six times (6.6) higher than those of direct plating on DRBC, and those of enrichment with a phenolic mix. The sequencing of ITS and LSU-rDNA confirmed the dominance of potentially pathogenic fungi from the family Herpotrichiellaceae and Exophiala xenobiotica. Moreover, other opportunistic species were found, including E. opportunistica, E. oligosperma, E. phaeomuriformis, and Rhinocladiella similis. The recurrent presence of E. crusticola, Knufia epidermidis, Aureobasidium melanogenum, Cladosporium spp., and Scolecobasidium spp. was also recorded. Interestingly, 12% of total isolates, corresponding to 50% of taxa found (16/32), represent new species. All the novel taxa in this study were isolated by LCI. These findings suggest that black fungal diversity in hydrocarbon-rich niches remains largely unexplored and that LCI can be an efficient tool for further investigations.

Case report: subcutaneous Exophiala xenobiotica infection successfully treated with a combined medical and surgical approach

Case report: subcutaneous Exophiala xenobiotica infection successfully treated with a combined medical and surgical approach

Selective isolation of agents of chromoblastomycosis from insect-associated environmental sources

Chromoblastomycosis is a neglected disease characterized by cutaneous, subcutaneous or disseminated lesions. It is considered an occupational infectious disease that affects mostly rural workers exposed to contaminated soil and vegetal matter. Lesions mostly arise after a traumatic inoculation of herpotrichiellaceous fungi from the Chaetothyriales order. However, the environmental niche of the agents of the disease remains obscure. Its association with insects has been predicted in a few studies. Therefore, the present work aimed to analyze if social insects, specifically ants, bees, and termites, provide a suitable habitat for the fungi concerned. The mineral oil flotation method was used to isolate the microorganisms. Nine isolates were recovered and phylogenetic analysis identified two strains as potential agents of chromoblastomycosis, i.e., Fonsecaea pedrosoi CMRP 3076, obtained from a termite nest (n = 1) and Rhinocladiella similis CMRP 3079 from an ant exoskeleton (n = 1). In addition, we also identified Fonsecaea brasiliensis CMRP 3445 from termites (n = 1), Exophiala xenobiotica CMRP 3077 from ant exoskeleton (n = 1), Cyphellophoraceae CMRP 3103 from bees (n = 1), Cladosporium sp. CMRP 3119 from bees (n = 1), Hawksworthiomyces sp. CMRP 3102 from termites (n = 1), and Cryptendoxyla sp. from termites (n = 2). The environmental isolate of F. pedrosoi CMRP 3076 was tested in two animal models, Tenebrio molitor and Wistar rat, for its pathogenic potential with fungal retention in T. molitor tissue. In the Wistar rat, the cells resembling muriform cells were observed 30 d after inoculation.

Curso clínico de micosis producidas por Exophiala xenobiotica en paciente trasplantado renal en el Hospital Universitario de Burgos

Las micosis por Exophiala xenobiotica comprenden un amplio espectro clínico en pacientes inmunosuprimidos, desde infecciones localizadas, hasta diseminadas. Son incluidas como etiología de las feohifomicosis, actualmente consideradas como infecciones fúngicas emergentes en pacientes trasplantados de órgano sólido. Presentamos 2 casos de micosis por Eexophiala xenobiotica en paciente trasplantado renal, una micosis cutánea localizada y una infección sistémica con afectación del sistema nervioso central

Amine Transaminase fromExophiala Xenobiotica—Crystal Structure and Engineering of a Fold IV Transaminase that Naturally Converts Biaryl Ketones

Amine Transaminase from<i>Exophiala Xenobiotica</i>—Crystal Structure and Engineering of a Fold IV Transaminase that Naturally Converts Biaryl Ketones

Amine Transaminase from Exophiala Xenobiotica – Crystal Structure and Engineering of a Fold IV Transaminase that Naturally Converts Biaryl Ketones

Amine Transaminase from Exophiala Xenobiotica – Crystal Structure and Engineering of a Fold IV Transaminase that Naturally Converts Biaryl Ketones

Black yeast diversity on creosoted railway sleepers changes with ambient climatic conditions.

The environmental isolation of opportunistic pathogenic black yeasts, which are responsible for a wide spectrum of human infections, is essential to understanding the ecology of clinical fungi. Extreme outdoor environments polluted with aromatic hydrocarbons support the growth of black yeasts in unlikely places, such as railway sleepers. However, there are limited data concerning the diversity of these fungi growing on polluted railway sleepers. In this investigation, we examined 845 railway sleeper samples, obtained from 11 Turkish cities representing altitudes from 25 to 1,893 m, and inoculated the samples onto mycological media for the isolation of black yeasts. Ninety-four samples (11.1 %) yielded positive results for black yeast, with creosoted oak sleepers having a significantly higher number of isolates than concrete sleepers (p < 0.05). Identification based on the ribosomal DNA (rDNA) internal transcribed spacer region revealed the highest prevalence of Exophiala phaeomuriformis, followed by Exophiala dermatitidis, Exophiala heteromorpha, Exophiala xenobiotica, and Exophiala crusticola. This study revealed that railway sleepers harboring black yeasts were predominantly (>75 %) populated with thermophilic species. We observed that altitude might have a significant effect on species diversity. Briefly, E. phaeomuriformis exhibited growth over a wide altitude range, from 30 to 1,893 m. In contrast, E. dermatitidis had a remarkable aversion to low altitudes and exhibited maximum growth at 1,285 m. In conclusion, we speculate that one can predict what species will be found on railway sleepers and their probability and that species diversity primarily depends on sleeper type and altitude height. We believe that this study can contribute new insights into the ecology of black yeasts on railway sleepers and the railway factors that influence their diversity.

Isolation and Screening of Black Fungi as Degraders of Volatile Aromatic Hydrocarbons

Black fungi reported as degraders of volatile aromatic compounds were isolated from hydrocarbon-polluted sites and indoor environments. Several of the species encountered are known opportunistic pathogens or are closely related to pathogenic species causing severe mycoses, among which are neurological infections in immunocompetent individuals. Given the scale of the problem of environmental pollution and the phylogenetic relation of aromate-degrading black fungi with pathogenic siblings, it is of great interest to select strains able to mineralize these substrates efficiently without any risk for public health. Fifty-six black strains were obtained from human-made environments rich in hydrocarbons (gasoline car tanks, washing machine soap dispensers) after enrichment with some phenolic intermediates of toluene and styrene fungal metabolism. Based on ITS sequencing identification, the majority of the obtained isolates were members of the genus Exophiala. Exophiala xenobiotica was found to be the dominant black yeast present in the car gasoline tanks. A higher biodiversity, with three Exophiala species, was found in soap dispensers of washing machines. Strains obtained were screened using a 2,6-dichlorophenol-indophenol (DCPIP) assay, optimized for black fungi, to assess their potential ability to degrade toluene. Seven out of twenty strains tested were able to use toluene as carbon source.

Subcutaneous phaeohyphomycosis caused by Exophiala jeanselmei in collagen disease patient

Phaeohyphomycosis is a rare fungal infection that is more commonly associated with compromised patients. We present herein an 81-year-old man with collagen disease and chronic interstitial pneumonia who developed subcutaneous phaeohyphomycosis caused by Exophiala jeanselmei. The main pathogen of phaeohyphomycosis had been considered to be E.jeanselmei complex. This has recently been divided into several species by using a molecular technique. The main pathogen of phaeohyphomycosis is Exophiala xenobiotica, and E.jeanselmei is rather a rare pathogen of this disease. Although p.o. itraconazole and terbinafine administration was not effective for this patient, these antifungal agents were used for preventing systemic dissemination in this immunocompromised host.

Antifungal therapies in murine disseminated phaeohyphomycoses caused by Exophiala species

We have evaluated the efficacy of posaconazole, itraconazole and amphotericin B in murine models of disseminated infection caused by Exophiala spp. Immunosuppressed mice were treated with posaconazole at 10, 20 or 40 mg/kg/day orally (po), amphotericin B at 1.5 mg/kg/day intraperitoneally (ip) or itraconazole at 50 mg/kg/day po. Treatment began 1 day after infection and continued for 7 days post-infection. Two strains of each of the three most relevant clinical species, i.e. Exophiala dermatitidis, Exophiala oligosperma and Exophiala xenobiotica, were tested. Posaconazole showed the highest efficacy in mice infected with E. dermatitidis, the only species that showed a high neurotropism, while the three drugs showed a similarly good activity against E. oligosperma and E. xenobiotica infections. The results suggest that posaconazole may have a clinical role in the treatment of disseminated infections caused by Exophiala species, especially in those with CNS invasion.

Isolation and Identification of Black Yeasts by Enrichment on Atmospheres of Monoaromatic Hydrocarbons

Black yeast members of the Herpotrichiellaceae present a complex ecological behavior: They are often isolated from rather extreme environments polluted with aromatic hydrocarbons, while they are also regularly involved in human opportunistic infections. A selective technique to promote the in vitro growth of herpotrichiellaceous fungi was applied to investigate their ecophysiology. Samples from natural ecological niches and man-made environments that might contain black yeasts were enriched on an inert solid support at low humidity and under a controlled atmosphere rich in volatile aromatic hydrocarbons. Benzene, toluene, and xylene were provided separately as the sole carbon and energy source via the gas phase. The assayed isolation protocol was highly specific toward mesophilic Exophiala species (70 strains of this genus out of 71 isolates). Those were obtained predominantly from creosote-treated railway ties (53 strains), but isolates were also found on wild berries (11 strains) and in guano-rich soil samples (six strains). Most of the isolates were obtained on toluene (43 strains), but enrichments on xylene and benzene also yielded herpotrichiellaceous fungi (17 and 10 isolates, respectively). Based upon morphological characterizations and DNA sequences of the full internal transcriber spacers (ITS) and the 8.5S rRNA genes, the majority of the obtained isolates were affiliated to the recently described species Exophiala xenobiotica (32 strains) and Exophiala bergeri (nine strains). Members of two other phylogenetic groups (24 and two strains, respectively) somewhat related to E. bergeri were also found, and a last group (three strains) corresponded to an undescribed Exophiala species.

A Case of Phaeohyphomycosis Caused by Exophiala xenobiotica during Treatment with Oral Steroids and Cyclophosphamides

A Case of Phaeohyphomycosis Caused by <i>Exophiala xenobiotica</i> during Treatment with Oral Steroids and Cyclophosphamides

Exophiala xenobiotica infection in cultured striped jack, Pseudocaranx dentex (Bloch &amp; Schneider), in Japan

This report describes Exophiala infection in cultured striped jack, Pseudocaranx dentex, in Japan in 2005. One hundred out of 35,000 fish died per day and mortalities continued for 1 month. Diseased fish showed swelling of the abdomen and kidney distension. Numerous septate hyphae, pale brown in colour, were seen in kidney in squash preparations. Histology revealed abundant fungal hyphae and conidia in gill, heart and kidney. Fungal hyphae were accompanied by cell necrosis and influx of inflammatory, mainly mononuclear cells. The fungus isolated from the diseased fish had septate hyphae, pale brown in colour and 1.8-3.0 microm in diameter. Conidiogenous cells were conspicuous annellides, short or cylindrical or fusiform in shape. Conidia were one-celled, ellipsoidal with smooth walls, accumulated in balls at the apices of annellides that tended to slide down, 1.5-2.0 microm in width and 3.0-5.0 microm in length. The fungus was classified into the genus Exophiala based on its morphology and as Exophiala xenobiotica based on the sequences of the ITS 1-5.8S-ITS 2 regions of rDNA. This is the first record of this fungus in a marine fish.