RESUMEN
The black fungus Exophiala causes a wide range of infections from superficial to subcutaneous, but also invasive fungal infections in immunocompromised patients as well as healthy individuals. In addition, Exophiala, is a common colonizer of the air ways of patients with cystic fibrosis. However, the source of infection and mode of transmission is still unclear. The aim of this study was to investigate the presence of Exophiala in samples collected from Swedish indoor environments. We found that the Exophiala species were commonly found in dishwashers and that Exophiala dermatitidis was the most common Exophiala species, being identified in 70% (26 out of the 37) of samples. Almost all E. dermatitidis isolates had the ability to grow at 42 °C (P = 0.0002) and were catalase positive. Voriconazole and posaconazole exhibited the lowest MICs, while caspofungin and anidulafungin lack the antifungal activities in vitro. Future studies are needed to illuminate the transmission mode of the fungi.
Asunto(s)
Antifúngicos , Farmacorresistencia Fúngica , Exophiala , Pruebas de Sensibilidad Microbiana , Exophiala/efectos de los fármacos , Exophiala/aislamiento & purificación , Antifúngicos/farmacología , Humanos , Feohifomicosis/microbiología , Feohifomicosis/tratamiento farmacológico , Composición Familiar , Voriconazol/farmacología , Suecia , TriazolesRESUMEN
OBJECTIVE: To describe a patient diagnosed with Exophiala jeanselmei keratitis. METHODS: We report a case of a patient who developed infectious keratitis following laser in situ keratomileusis and chronic topical steroid use for approximately six months in both eyes. An atypical infiltrate containing dark pigmentation was noted in the left eye on the initial presentation. During treatment, the infiltrates of the right eye began to exhibit a similar pigmentation. RESULTS: Early treatment with topical antifungals was initiated in the left eye and later in the right eye once culture results returned. Both eyes recovered with good vision after approximately one month. CONCLUSIONS: Patients treated with postoperative topical corticosteroids should be cautioned of potential adverse effects of chronic use and have close follow-up. If infectious keratitis develops, particularly after two weeks, then atypical organisms, such as fungi, should be considered. In addition, our case highlights the significance of recognizing and associating dark-pigmentation with fungal etiologies.
Asunto(s)
Antifúngicos , Exophiala , Infecciones Fúngicas del Ojo , Queratitis , Queratomileusis por Láser In Situ , Adulto , Humanos , Antifúngicos/uso terapéutico , Úlcera de la Córnea/microbiología , Úlcera de la Córnea/tratamiento farmacológico , Úlcera de la Córnea/diagnóstico , Úlcera de la Córnea/etiología , Exophiala/aislamiento & purificación , Infecciones Fúngicas del Ojo/microbiología , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Infecciones Fúngicas del Ojo/diagnóstico , Glucocorticoides/uso terapéutico , Glucocorticoides/administración & dosificación , Queratitis/microbiología , Queratitis/diagnóstico , Queratitis/tratamiento farmacológico , Queratitis/etiología , Queratomileusis por Láser In Situ/efectos adversos , Feohifomicosis/microbiología , Feohifomicosis/diagnóstico , Feohifomicosis/tratamiento farmacológicoRESUMEN
Hyalohyphomycosis and phaeohyphomycosis are groups of mycoses caused by several agents and show different clinical manifestations. We report a case of an immunocompromised patient who presented rare manifestations of opportunistic mycoses: mycetoma-like hyalohyphomycosis on his right foot caused by Colletotrichum gloeosporioides, followed by cutaneous phaeohyphomycosis on his right forearm caused by Exophiala oligosperma. Further to the rarity of this case, the patient's lesion on the foot shows that the clinical aspects of mycetomas could falsely appear in other fungal infections similar to hyalohyphomycosis. We also show that the muriform cells that were seen in the direct and anatomopathological examination of the skin are not pathognomonic of chromoblastomycosis, as observed in the lesion of the patient's forearm.
Asunto(s)
Cromoblastomicosis , Micetoma , Humanos , Masculino , Cromoblastomicosis/patología , Cromoblastomicosis/diagnóstico , Cromoblastomicosis/microbiología , Cromoblastomicosis/tratamiento farmacológico , Micetoma/patología , Micetoma/microbiología , Micetoma/diagnóstico , Micetoma/tratamiento farmacológico , Diagnóstico Diferencial , Huésped Inmunocomprometido , Hialohifomicosis/patología , Hialohifomicosis/microbiología , Hialohifomicosis/diagnóstico , Exophiala/aislamiento & purificación , Persona de Mediana EdadRESUMEN
The genus Exophiala is polymorphic, able to transition between yeast, hyphal and pseudohyphal forms. Species of the genus Exophiala are ubiquitous fungi that are distributed in various environments around the world. During a survey of fungal diversity in the gut of amphipods (Floresorchestia amphawaensis and undescribed Dogielinotid amphipods) from the Amphawa estuary, Samut Songkhram province, Thailand, five black yeast strains (DMKU-MG01, DMKU-MG07, DMKU-MG08, DMKU-HG10 and DMKU-FG04) were identified as representing a novel taxon on the basis of a combination of morphological and molecular phylogenetic features. The five strains did not produce filamentous hyphae or pseudohyphae. Only budding yeast cells were observed. On the basis of the phenotypic characteristics and the results of molecular analyses of the D1/D2 region of the large subunit (LSU) rRNA gene and the internal transcribed spacer (ITS) region, the five strains were identified as representing a novel species via applied nucleotide pairwise analysis. They differed from the most closely related species Exophiala alcalophiala by 3.54â% nucleotide substitutions (20 nucleotide substitutions in 572 bp) in the D1/D2 domains of the LSU rRNA gene. Moreover, the sequences of the ITS region of the five strains differed from those of the most closely related species E. alcalophiala, by 7.44-9.62â% nucleotide substitutions, and Exophiala halophiala, by 7.2-7.53â% nucleotide substitutions. The results of phylogenetic analyses based on the concatenated sequences of the ITS regions and the D1/D2 domains of the LSU rRNA gene confirmed that the five black yeast strains represented a single novel species of the genus Exophiala. In this study, Exophiala amphawaensis sp. nov. is proposed to accommodate these strains. The holotype is TBRC 15626T and the isotype is PYCC9020. The MycoBank accession number of the novel species is MB 851477.
Asunto(s)
Anfípodos , ADN de Hongos , ADN Espaciador Ribosómico , Exophiala , Filogenia , Análisis de Secuencia de ADN , Animales , Tailandia , Anfípodos/microbiología , ADN de Hongos/genética , ADN Espaciador Ribosómico/genética , Exophiala/genética , Exophiala/aislamiento & purificación , Exophiala/clasificación , Técnicas de Tipificación Micológica , Tracto Gastrointestinal/microbiologíaRESUMEN
Pus discharge containing black granular materials (1-2 mm in diameter) was found in the abdominal skin of a 13-year-old sterilized female cat. Abdominal ultrasonography revealed a large intra-abdominal mass with abundant blood flow beneath the skin lesion. Laparotomy revealed a large mass that adhered to the spleen and left kidney. Similar small lesions were found in the abdominal wall and mesentery. The masses were surgically removed along with the spleen and kidney. Histopathologically, the mass lesions consisted of granulomas with lesional pigmented fungi, and the cat was diagnosed with phaeohyphomycosis. Uisng genetic analysis, the Exophiala dermatitidis was identified as the causative pathogen.
Asunto(s)
Enfermedades de los Gatos , Exophiala , Feohifomicosis , Animales , Feohifomicosis/veterinaria , Feohifomicosis/microbiología , Feohifomicosis/diagnóstico , Feohifomicosis/patología , Enfermedades de los Gatos/microbiología , Enfermedades de los Gatos/diagnóstico , Enfermedades de los Gatos/patología , Femenino , Gatos , Exophiala/aislamiento & purificaciónRESUMEN
Exophiala is a black fungi of the family Herpotrichiellaceae that can be found in a wide range of environments like soil, water and the human body as potential opportunistic pathogen. Some species are known to be extremophiles, thriving in harsh conditions such as deserts, glaciers, and polluted habitats. The identification of novel Exophiala species across diverse environments underlines the remarkable biodiversity within the genus. However, its classification using traditional phenotypic and phylogenetic analyses has posed a challenges. Here we describe a novel taxon, Exophiala chapopotensis sp. nov., strain LBMH1013, isolated from oil-polluted soil in Mexico, delimited according to combined morphological, molecular, evolutionary and statistics criteria. This species possesses the characteristic dark mycelia growing on PDA and tends to be darker in the presence of hydrocarbons. Its growth is dual with both yeast-like and hyphal forms. LBMH1013 differs from closely related species such as E. nidicola due to its larger aseptate conidia and could be distinguished from E. dermatitidis and E. heteromorpha by its inability to thrive above 37°C or 10% of NaCl. A comprehensive genomic analyses using up-to-date overall genome relatedness indices, several multigene phylogenies and molecular evolutionary analyzes using Bayesian speciation models, further validate its species-specific transition from all current Exophiala/Capronia species. Additionally, we applied the phylophenetic conceptual framework to delineate the species-specific hypothesis in order to incorporate this proposal within an integrative taxonomic framework. We believe that this approach to delimit fungal species will also be useful to our peers.
Asunto(s)
Ascomicetos , Exophiala , Humanos , Exophiala/genética , Saccharomyces cerevisiae , Filogenia , México , Teorema de BayesRESUMEN
The opportunistic black yeast-like fungus Exophiala dermatitidis frequently colonizes the respiratory tract of cystic fibroses (CF) patients. Additionally, it can cause superficial, systemic, and cerebral forms of phaeohyphomycoses. The objective of this study was to develop and apply a microsatellite or short tandem repeat (STR) genotyping scheme for E. dermatitidis. In total, 82 E. dermatitidis isolates from various geographic origins (environmental = 9, CF = 63, invasive isolates = 9, melanin-deficient mutant = 1) were included in this study. After next-generation sequencing of a reference strain and sequence filtering for microsatellites, six STR markers were selected and amplified in two multiplex PCR reactions. The included isolates were discriminated in a genetic cluster analysis using the Pearson algorithm to reveal the relatedness of the isolates. The E. dermatitidis isolates clustered on basis of both, their source and their origin. The invasive isolates from Asia were unrelated to isolates from CF. Nearly all environmental isolates were grouped separately from patients' isolates. The Simpson index was 0.94. In conclusion, we were able to establish a STR genotyping scheme for investigating population genomics of E. dermatitidis.
Asunto(s)
Fibrosis Quística , Exophiala , Humanos , Exophiala/genética , Asia , Análisis por Conglomerados , Repeticiones de MicrosatéliteRESUMEN
Exophiala dermatitidis is a relatively common environmental black yeast with a worldwide distribution that rarely causes fungal infection. Here, we report a case of a 6-year-old girl with central nervous system (CNS) encephalitis caused by E. dermatitidis and Angiostrongylus cantonensis. E. dermatitidis was identified by both cerebrospinal fluid culture and metagenomic next-generation sequencing (mNGS). Angiostrongylus cantonensis infection was confirmed by an enzyme linked immunosorbent assay (ELISA). Whole exome sequencing showed that this previously healthy girl carried a homozygous CARD9 mutation for c.820dupG (p.D274Gfs*61) that underlies invasive fungal and parasite infections. We chose glucocortieoid pulse therapy and anti-infective therapy based on the initial results of laboratory examination and cranial MRI images. With the aggravation of the disease and the evidence of the subsequent etiologic test, the combination of antifungal antiparasitic treatments (voriconazole, fluorocytosine and amphotericin B) were actively used. Unfortunately, the girl finally died due to severe systemic infection. mNGS performs a potential value for diagnosing rare CNS infections, and autosomal recessive CARD9 deficiency should be considered in patient with fatal invasive fungal infections.
Asunto(s)
Angiostrongylus cantonensis , Candidiasis Mucocutánea Crónica , Exophiala , Niño , Animales , Femenino , Humanos , Angiostrongylus cantonensis/genética , Sistema Nervioso Central , Exophiala/genética , Proteínas Adaptadoras de Señalización CARD/genéticaRESUMEN
Fungal infective endocarditis, although rare, carries a high mortality risk. We present a case of successful multidisciplinary management of Exophiala dermatitidis infective endocarditis in an immunocompetent male with a bio-prosthetic mitral valve. This case highlights the clinical presentation and provides valuable treatment insights into this rare fungal entity. Prompt consideration of fungal pathogens in predisposed patients, expedited detection through non-culture-based tests, and a combined surgical and prolonged antifungal approach are pivotal.
Asunto(s)
Endocarditis Bacteriana , Endocarditis , Exophiala , Enfermedades de las Válvulas Cardíacas , Prótesis Valvulares Cardíacas , Micosis , Humanos , Masculino , Válvula Mitral/cirugía , Endocarditis Bacteriana/cirugía , Endocarditis/diagnóstico , Endocarditis/tratamiento farmacológico , Endocarditis/microbiología , Enfermedades de las Válvulas Cardíacas/cirugía , Prótesis Valvulares Cardíacas/efectos adversosAsunto(s)
Humanos , Femenino , Persona de Mediana Edad , Feohifomicosis/diagnóstico por imagen , Exophiala , Diabetes Mellitus/tratamiento farmacológico , Complicaciones de la Diabetes , Vildagliptina , Metformina , Pacientes Internos , Examen Físico , Enfermedades Transmisibles , Microbiología , Técnicas Microbiológicas , Hongos , MicosisRESUMEN
In cystic fibrosis (CF) patients, fungal colonization of the respiratory tract is frequently found. Aspergillus fumigatus, Scedosporium genus, and Exophiala dermatitidis are the most commonly isolated moulds from the respiratory tract secretions of CF patients. The aim of this 5-year surveillance study was to identify trends in species distribution and susceptibility patterns of 212 mould strains identified as Aspergillus spp., Scedosporium spp., and Exophiala spp., isolated from sputum of 63 CF patients who received long-term therapy with itraconazole (ITR) and/or voriconazole (VRC). The Aspergillus isolates were identified as members of the sections Fumigati (n = 130), Flavi (n = 22), Terrei (n = 20), Nigri (n = 8), Nidulantes (n = 1), and Usti (n = 1). Among the 16 species of the genus Scedosporium, 9 were S. apiospermum, 3 S. aurantiacum, and 4 S. boydii. Among the 14 Exophiala species, all were molecularly identified as E. dermatitidis. Overall, 94% (15/16) of Scedosporium spp., 50% (7/14) of E. dermatitidis, and 7.7% (14/182) of Aspergillus spp. strains showed high MIC values (≥8 µg/ml) for at least one antifungal. Particularly, 8.9% (19/212) of isolates showed high MIC values for amphotericin B, 11.7% (25/212) for ITR, 4.2% (9/212) for VRC, and 3.3% (7/212) for posaconazole. In some cases, such as some A. fumigatus and E. dermatitidis isolates recovered from the same patient, susceptibility to antifungal azoles decreased over time. We show that the use of azoles for a long time in CF patients causes the selection/isolation of mould strains with higher MIC values.
The use of azoles for a long time in cystic fibrosis patients causes the selection/isolation of Aspergillus, Scedosporium, and Exophiala species with higher MIC values.
Asunto(s)
Fibrosis Quística , Exophiala , Scedosporium , Animales , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Anfotericina B/farmacología , Anfotericina B/uso terapéutico , Fibrosis Quística/complicaciones , Fibrosis Quística/veterinaria , Exophiala/genética , Triazoles/farmacología , Triazoles/uso terapéutico , Itraconazol , Voriconazol/farmacología , Voriconazol/uso terapéutico , Aspergillus , AzolesRESUMEN
Exophiala spinifera is a rare dematiaceous fungus causing cutaneous, subcutaneous and disseminated phaeohyphomycosis (PHM). Standard antifungal therapy for PHM is still uncertain. Here, we report a case of a Chinese male with PHM caused by E. spinifera, who received significant clinical improvement after the treatment with oral itraconazole and terbinafine. With the aim of evaluating the antifungal therapy for PHM caused by E. spinifera, a detailed review was performed.
Asunto(s)
Exophiala , Feohifomicosis , Masculino , Humanos , Itraconazol/uso terapéutico , Terbinafina/uso terapéutico , Antifúngicos/uso terapéutico , Feohifomicosis/diagnóstico , Feohifomicosis/tratamiento farmacológico , Feohifomicosis/microbiologíaRESUMEN
The genetic disease cystic fibrosis (CF) frequently leads to chronic lung infections by bacteria and fungi. We identified three individuals with CF with persistent lung infections dominated by Clavispora (Candida) lusitaniae. Whole-genome sequencing analysis of multiple isolates from each infection found evidence for selection for mutants in the gene MRS4 in all three distinct lung-associated populations. In each population, we found one or two unfixed, non-synonymous mutations in MRS4 relative to the reference allele found in multiple environmental and clinical isolates including the type strain. Genetic and phenotypic analyses found that all evolved alleles led to loss of function (LOF) of Mrs4, a mitochondrial iron transporter. RNA-seq analyses found that Mrs4 variants with decreased activity led to increased expression of genes involved in iron acquisition mechanisms in both low iron and replete iron conditions. Furthermore, surface iron reductase activity and intracellular iron were much higher in strains with Mrs4 LOF variants. Parallel studies found that a subpopulation of a CF-associated Exophiala dermatitidis infection also had a non-synonymous LOF mutation in MRS4. Together, these data suggest that MRS4 mutations may be beneficial during chronic CF lung infections in diverse fungi, perhaps, for the purposes of adaptation to an iron-restricted environment with chronic infections. IMPORTANCE The identification of MRS4 mutations in Clavispora (Candida) lusitaniae and Exophiala dermatitidis in individuals with cystic fibrosis (CF) highlights a possible adaptive mechanism for fungi during chronic CF lung infections. The findings of this study suggest that loss of function of the mitochondrial iron transporter Mrs4 can lead to increased activity of iron acquisition mechanisms, which may be advantageous for fungi in iron-restricted environments during chronic infections. This study provides valuable information for researchers working toward a better understanding of the pathogenesis of chronic lung infections and more effective therapies to treat them.
Asunto(s)
Fibrosis Quística , Exophiala , Humanos , Fibrosis Quística/complicaciones , Fibrosis Quística/microbiología , Infección Persistente , Hongos/genética , Hongos/metabolismo , Pulmón/metabolismo , Hierro/metabolismoRESUMEN
The initiation of this study relies on a targeted genome-mining approach to highlight the presence of a putative vanadium-dependent haloperoxidase-encoding gene in the deep-sea hydrothermal vent fungus Hortaea werneckii UBOCC-A-208029. To date, only three fungal vanadium-dependent haloperoxidases have been described, one from the terrestrial species Curvularia inaequalis, one from the fungal plant pathogen Botrytis cinerea, and one from a marine derived isolate identified as Alternaria didymospora. In this study, we describe a new vanadium chloroperoxidase from the black yeast H. werneckii, successfully cloned and overexpressed in a bacterial host, which possesses higher affinity for bromide (Km = 26 µM) than chloride (Km = 237 mM). The enzyme was biochemically characterized, and we have evaluated its potential for biocatalysis by determining its stability and tolerance in organic solvents. We also describe its potential three-dimensional structure by building a model using the AlphaFold 2 artificial intelligence tool. This model shows some conservation of the 3D structure of the active site compared to the vanadium chloroperoxidase from C. inaequalis but it also highlights some differences in the active site entrance and the volume of the active site pocket, underlining its originality.
Asunto(s)
Ascomicetos , Cloruro Peroxidasa , Exophiala , Respiraderos Hidrotermales , Cloruro Peroxidasa/genética , Cloruro Peroxidasa/química , Cloruro Peroxidasa/metabolismo , Exophiala/metabolismo , Saccharomyces cerevisiae/metabolismo , Vanadio/metabolismo , Inteligencia Artificial , Ascomicetos/genéticaRESUMEN
Exophiala species cause chromoblastomycosis, mycetoma, and phaeohyphomycosis, which are occasionally fatally in immunocompromised patients. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) provides rapid and accurate examination of isolated bacteria and some fungal isolates, but the preparation method for filamentous fungi is complicated. In this study, 31 clinical isolates of Exophiala spp. in Japan were identified by MALDI-TOF MS with a library enriched by adding data. To simplify the sample preparation method, two modified methods were compared with the standard method for filamentous fungi. The agar cultivation sample preparation method reduced the time required for liquid culture and was considered suitable for clinical use. In 30 of 31 clinical isolates of Exophiala spp., the species identified by MALDI-TOF MS with the highest score matched the species identified by sequencing the internal transcribed spacer region. Exophiala dermatitidis, E. lecanii-corni, and E. oligosperma were identified above the genus level, while E. jeanselmei and E. xenobiotica were often not identified at the species level. The identification scores tended to be lower for less-registered strains in the in-house library. It is suggested that library enrichment and the modified preparation method may facilitate early diagnosis of rare fungal infections by Exophiala spp. in clinical laboratories using MALDI-TOF MS.
Asunto(s)
Exophiala , Micosis , Humanos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Japón , HongosRESUMEN
Individuals with cystic fibrosis (CF) are susceptible to chronic lung infections that lead to inflammation and irreversible lung damage. While most respiratory infections that occur in CF are caused by bacteria, some are dominated by fungi such as the slow-growing black yeast Exophiala dermatitidis. Here, we analyze isolates of E. dermatitidis cultured from two samples, collected from a single subject 2 years apart. One isolate genome was sequenced using long-read Nanopore technology as an in-population reference to use in comparative single nucleotide polymorphism and insertion-deletion variant analyses of 23 isolates. We then used population genomics and phylo-genomics to compare the isolates to each other as well as the reference genome strain E. dermatitidis NIH/UT8656. Within the CF lung population, three E. dermatitidis clades were detected, each with varying mutation rates. Overall, the isolates were highly similar suggesting that they were recently diverged. All isolates were MAT 1-1, which was consistent with their high relatedness and the absence of evidence for mating or recombination between isolates. Phylogenetic analysis grouped sets of isolates into clades that contained isolates from both early and late time points indicating there are multiple persistent lineages. Functional assessment of variants unique to each clade identified alleles in genes that encode transporters, cytochrome P450 oxidoreductases, iron acquisition, and DNA repair processes. Consistent with the genomic heterogeneity, isolates showed some stable phenotype heterogeneity in melanin production, subtle differences in antifungal minimum inhibitory concentrations, and growth on different substrates. The persistent population heterogeneity identified in lung-derived isolates is an important factor to consider in the study of chronic fungal infections, and the analysis of changes in fungal pathogens over time may provide important insights into the physiology of black yeasts and other slow-growing fungi in vivo.
Asunto(s)
Fibrosis Quística , Exophiala , Fibrosis Quística/complicaciones , Fibrosis Quística/microbiología , Filogenia , Exophiala/genética , PulmónAsunto(s)
Exophiala , Fallo Renal Crónico , Trasplante de Riñón , Scedosporium , Voriconazol , Humanos , Exophiala/efectos de los fármacos , Trasplante de Riñón/efectos adversos , Scedosporium/efectos de los fármacos , Receptores de Trasplantes , Voriconazol/administración & dosificación , Voriconazol/uso terapéutico , Masculino , Adulto , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/cirugía , Feohifomicosis/tratamiento farmacológicoRESUMEN
Black yeasts are polyextremotolerant fungi that contain high amounts of melanin in their cell wall and maintain a primar yeast form. These fungi grow in xeric, nutrient depletes environments which implies that they require highly flexible metabolisms and have been suggested to contain the ability to form lichen-like mutualisms with nearby algae and bacteria. However, the exact ecological niche and interactions between these fungi and their surrounding community are not well understood. We have isolated 2 novel black yeasts from the genus Exophiala that were recovered from dryland biological soil crusts. Despite notable differences in colony and cellular morphology, both fungi appear to be members of the same species, which has been named Exophiala viscosa (i.e. E. viscosa JF 03-3 Goopy and E. viscosa JF 03-4F Slimy). A combination of whole genome sequencing, phenotypic experiments, and melanin regulation experiments have been performed on these isolates to fully characterize these fungi and help decipher their fundamental niche within the biological soil crust consortium. Our results reveal that E. viscosa is capable of utilizing a wide variety of carbon and nitrogen sources potentially derived from symbiotic microbes, can withstand many forms of abiotic stresses, and excretes melanin which can potentially provide ultraviolet resistance to the biological soil crust community. Besides the identification of a novel species within the genus Exophiala, our study also provides new insight into the regulation of melanin production in polyextremotolerant fungi.