Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 608
Filtrar
1.
Mycoses ; 64(11): 1328-1333, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34411353

RESUMO

BACKGROUND: Exophiala is the main genus of black fungi comprising numerous opportunistic species. Data on antifungal susceptibility of Exophiala isolates are limited, while infections are potentially fatal. MATERIALS AND METHODS: In vitro activities of eight antifungal drugs (AMB, five azoles, two echinocandins) against 126 clinical (n = 76) and environmental (n = 47) isolates from around the world were investigated. E. oligosperma (n = 58), E. spinifera (n = 33), E. jeanselmei (n = 14) and E. xenobiotica (n = 21) were included in our dataset. RESULTS: The resulting MIC90 s of all strains were as follows, in increasing order: posaconazole 0.063 µg/ml, itraconazole 0.125 µg/ml, voriconazole and amphotericin B 1 µg/ml, isavuconazole 2 µg/ml, micafungin and caspofungin 4 µg/ml, and fluconazole 64 µg/ml. Posaconazole, itraconazole and micafungin were the drugs with the best overall activity against Exophiala species. Fluconazole could not be considered as a treatment choice. No significant difference could be found among antifungal drug activities between these four species, neither in clinical nor in environmental isolates. CONCLUSION: Antifungal susceptibility data for Exophiala spp. are crucial to improve the management of this occasionally fatal infection and the outcome of its treatment.


Assuntos
Antifúngicos/farmacologia , Microbiologia Ambiental , Exophiala/efeitos dos fármacos , Feoifomicose/microbiologia , Animais , Antifúngicos/classificação , Antifúngicos/uso terapêutico , Exophiala/classificação , Exophiala/genética , Humanos , Testes de Sensibilidade Microbiana , Feoifomicose/tratamento farmacológico
2.
Front Cell Infect Microbiol ; 11: 686120, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34277470

RESUMO

Introduction: Exophiala spp. are important opportunist pathogens causing subcutaneous or even fatal disseminated infections in otherwise both immunosuppressed and healthy individuals but there are no systematic studies on the isolates of Exophiala species from India. Methods: Twenty-four isolates of Exophiala species were retrieved from the National Culture Collection of Pathogenic Fungi (NCCPF) and identified phenotypically and by molecular methods (ITS region sequencing) followed by antifungal susceptibility testing (AFST) as per CLSI-M38A3 guidelines. A review of the literature of cases from India was performed up to 1st January 2021 using the Medline and Cochrane database. Results: E. dermatitidis (n = 8), E. jeanselmei (n = 6), E. spinifera (n = 6), E. mesophila (n = 1), E. oligosperma (n = 1), E. xenobiotica (n = 1) were identified and the sequencing of ITS, ß-tubulin and ß-actin revealed a novel species, E. arunalokei sp. nov. (n = 1). The ITS sequence phylogram of E. jeanselmei revealed that the majority (83%) formed a separate cluster close to type A while majority (75%) of E. dermatitidis were type B. The MIC50 (mg/L) of amphotericin, itraconazole, voriconazole, micafungin, caspofungin, anidulafungin, and posaconazole, was 1, 0.25, 0.125, 0.12, 0.125, 0.062, and 0.062, respectively. Sixteen more cases were identified on the literature review and a significant association of E. dermatitidis with history of surgical procedures (p = 0.013), invasive disease (p = 0.032) and of E. mesophila with tuberculosis (p = 0.026) was seen. Conclusion: This, to the best of our knowledge is the first study from India elucidating the molecular and clinical characteristics of Exophiala species and the first Indian report of human infection due to E. xenobiotica and E. arunalokei.


Assuntos
Exophiala , Anfotericina B , Antifúngicos/farmacologia , Exophiala/genética , Humanos , Índia , Testes de Sensibilidade Microbiana
3.
J Infect Chemother ; 27(10): 1520-1524, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34215497

RESUMO

BACKGROUND: Central nervous system (CNS) infection due to Exophiala dermatitidis is rare and fatal, and primarily reported in immunocompromised patients or those with caspase recruitment domain-containing protein 9 deficiency. Herein, we describe a case of an otherwise healthy person (without underlying disease or gene deficiency) diagnosed with Exophiala dermatitidis meningoencephalitis. The patient achieved clinical remission under high-dose antifungal therapy in the first 14 months but died after 2 years of the therapy. CASE PRESENTATION: A 15-year-old student with headache and fever was admitted to our department. Lumbar puncture showed increased cerebrospinal fluid (CSF) pressure, moderately high CSF protein levels and cell counts, and a remarkable decrease in CSF glucose and chloride. Magnetic resonance imaging of the brain revealed multiple lesions and cerebral pia mater enhancement. CSF culture confirmed E. dermatitidis infection. We administered 4-week antifungal therapy of amphotericin B, but his CSF culture remained positive. After receiving the 12-week standard dose of voriconazole (200 mg q12h), the patient's CSF culture became negative, but his condition deteriorated with intracranial lesion enlargement. We administered a high-dose voriconazole therapy (600-800 mg per day) for 12 months, which led to clinical remission. The voriconazole dose was reduced due to adverse effects including hepatic dysfunction and hypokalemia, and the disease progressed with high intracranial pressure and epileptic seizures. CONCLUSIONS: CNS infection caused by E. dermatitidis is fatal and the most serious form of fungal infection. Initially, high-dose and long-term antifungal therapy could be effective. Gene defect and related antifungal immunodeficiency may be the most important pathogenic and lethal factor.


Assuntos
Exophiala , Meningoencefalite , Adolescente , Antifúngicos/uso terapêutico , Humanos , Meningoencefalite/tratamento farmacológico , Voriconazol/uso terapêutico
4.
Fungal Biol ; 125(8): 609-620, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34281654

RESUMO

Subterranean Cultural Heritage sites are frequently subject to biological colonization due to the high levels of humidity, even in conditions of low irradiance and oligotrophy. Here microorganisms form complex communities that may be dangerous through mineral precipitation, through the softening of materials or causing frequent surface discolorations. A reduction of contamination's sources along with the control of microclimatic conditions and biocide treatments (overall performed with benzalkonium chloride) are necessary to reduce microbial growths. Dark discolorations have been recorded in the painted Etruscan tombs of Tarquinia, two of which have been analyzed to collect taxonomical, physiological, and ecological information. Eighteen dark-pigmented fungi were isolated among a wider culturable fraction: nine from blackening areas and nine from door sealings, a possible route of contamination. Isolates belonged to three major groups: Chaetothyriales, Capnodiales (Family Cladosporiaceae), and Acremonium-like fungi. Exophiala angulospora and Cyphellophora olivacea, a novelty for hypogea, were identified, while others need further investigations as possible new taxa. The metabolic skills of the detected species showed their potential dangerousness for the materials. Their tolerance to benzalkonium chloride-based products suggested a certain favouring effect through the decreasing competitiveness of less resistant species. The type of covering of the dromos may influence the risk of outer contamination. Fungal occurrence can be favoured by root penetration.


Assuntos
Biodiversidade , Farmacorresistência Fúngica , Microbiologia Ambiental , Fungos , Ascomicetos/efeitos dos fármacos , Ascomicetos/fisiologia , Compostos de Benzalcônio/farmacologia , Exophiala/efeitos dos fármacos , Exophiala/fisiologia , Fungos/efeitos dos fármacos , Fungos/isolamento & purificação , Itália
5.
J Fish Dis ; 44(10): 1563-1577, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34148252

RESUMO

A broadening fish host range is affected by novel and known pigmented fungal pathogens. A review of 2,250 piscine submissions received by the Aquatic Pathology Service, University of Georgia, revealed 47 phaeohyphomycosis cases (2.1%), representing 34 bony and cartilaginous fish species. The majority involved bony fish (45/47, 95.7%) and were predominantly marine (41/47, 87.2%), with only a few freshwater species (4/47, 8.5%). Cartilaginous fish cases included two zebra sharks (Stegostoma fasciatum) (2/47, 4.3%). Northern seahorses (Hippocampus erectus) had the highest incidence overall (7/47, 14.9%). Culture and sequencing of the internal-transcribed spacer region of the rDNA (ITS), large ribosomal subunit gene D1/D2 domains (LSU) and the DNA polymerase II gene (RPB2) were performed for fungal identification when fresh tissue was obtainable. Exophiala, Ochroconis and Neodevriesia spp. were identified, with Exophiala as the most common fungal genus (8/11, 72.7%). Exophiala lecanii-corni and Neodevriesia cladophorae were described for the first time from fish. Microscopically, lesions were characterized by necrosis, granulomatous inflammation and angioinvasion most frequently affecting the skin/fin, skeletal muscle and kidneys. In this study of diverse aquarium-housed fish species, phaeohyphomycosis cases occurred sporadically and in rare outbreaks with variable pathologic presentations, tissue distributions and severities.


Assuntos
Ascomicetos/isolamento & purificação , Exophiala/isolamento & purificação , Doenças dos Peixes/epidemiologia , Peixes , Feoifomicose/veterinária , Animais , Doenças dos Peixes/microbiologia , Georgia/epidemiologia , Incidência , Feoifomicose/epidemiologia , Feoifomicose/microbiologia , Prevalência , Estudos Retrospectivos , Especificidade da Espécie
6.
Med Mycol J ; 62(2): 35-39, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34053978

RESUMO

We describe a case of recalcitrant phaeohyphomycosis caused by Exophiala lecanii-corni, which was previously reported as Exophiala jeanselmei, infection. A 63-year-old Japanese woman presented with a 15-year history of multiple pruritic erythematous patches and plaques on the face. Histopathological examination and fungal culture revealed phaeohyphomycosis by E. jeanselmei. The attempted treatments included 6 g/day 5-flucytosine (5-FC), 100 mg/day itraconazole (ITCZ), and local hyperthermia. 5-FC was effective initially, but the patient deteriorated after discontinuation. Subsequently, she was referred to our hospital. Histopathological examination showed granuloma with multinucleated giant cells with infiltrating fungal hyphae in the dermis. The causative fungus was finally identified as E. lecanii-corni by ribosomal RNA gene analysis. The patient improved after receiving 200 mg/day ITCZ orally for 15 months with local hyperthermia. In the present case, we confirmed the identification of E. lecanii-corni as the causative agent by molecular methods. We also emphasize the importance of combination therapy with antimycotic agents and local hyperthermia in phaeohyphomycosis.


Assuntos
Exophiala , Feoifomicose , Exophiala/genética , Feminino , Humanos , Pessoa de Meia-Idade , Feoifomicose/diagnóstico , Feoifomicose/tratamento farmacológico
7.
Fungal Biol ; 125(6): 459-468, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34024593

RESUMO

A clade where the most halotolerant fungus in the world - Hortaea werneckii, belongs (hereafter referred to as Hortaea werneckii lineage) includes five species: Hortaea werneckii, H. thailandica, Stenella araguata, Eupenidiella venezuelensis, and Magnuscella marina, of which the first species attracts increasing attention of mycologists. The species diversity and phylogenetic relationships within this lineage are weakly known. In this study two moderately halophilic black yeast strains were isolated from brine of graduation tower in Poland. Molecular phylogenetic analyses based on the rDNA ITS1-5.8S-ITS2 (=ITS), rDNA 28S D1-D2 (=LSU), and RNA polymerase II (rpb2) sequences showed that the two strains belong to Hortaea werneckii lineage but cannot be assigned to any described taxa. Accordingly, a new genus and species, Salinomyces and Salinomyces polonicus, are described for this fungus. Furthermore, molecular phylogenetic analyses have revealed that Hortaea thailandica is more closely related to S. polonicus than to H. werneckii. A new combination Salinomyces thailandicus is proposed for this fungus.


Assuntos
Ascomicetos , Filogenia , Ascomicetos/classificação , Ascomicetos/genética , DNA Fúngico/genética , DNA Ribossômico/genética , Exophiala/classificação , Exophiala/genética , Polônia , Especificidade da Espécie
8.
J Food Prot ; 84(9): 1582-1591, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-33878188

RESUMO

ABSTRACT: Black yeasts are a functional group that has caused spoilage in cold-filled and hot-filled beverages, as well as other water activity-controlled food products. We established quantitative thermoresistance parameters for the inactivation of 12 Aureobasidium and Exophiala isolates through isothermal experiments and a challenge study. Culture age (2 versus 28 days) variably affected the thermoresisitance among the black yeast strains. Variation in thermoresistance exists within each genus, but the two most resistant strains were the Exophiala isolates. The two most heat-resistant isolates were Exophiala phaeomuriformis FSL-E2-0572, with a D60-value of 7.69 ± 0.63 min in 28-day culture and Exophiala dermatitidis YB-734, with a D60-value of 16.32 ± 2.13 min in 28-day culture. Although these thermoresistance levels were, in some cases, greater than those for conidia and vegetative cells from other common food spoilage fungi, they were much more sensitive than the ascospores of heat-resistant molds most associated with spoilage of hot-filled products. However, given that black yeasts have caused spoilage in hot-filled products, we hypothesized that this intermediate degree of thermoresistance may support survival following introduction during active cooling before package seals have formed. A challenge study was performed in an acidic (apple cider) and water activity-controlled (maple syrup) product to evaluate survival. When apple cider was hot filled at 82°C, black yeast counts were reduced by 4.1 log CFU/mL 24 h after the heat treatment, but the survivors increased up to 6.7 log CFU/mL after 2 weeks. In comparison, the counts were below the detection limit after both 24 h and 14 days of shelf life in both products when filled at the boiling points. This suggests that ensuring water microbial quality in cooling tunnels and nozzle sanitation may be essential in mitigating the introduction of these fungi.


Assuntos
Ascomicetos , Microbiologia de Alimentos , Exophiala , Saccharomyces cerevisiae
9.
J Infect Chemother ; 27(9): 1360-1364, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33888421

RESUMO

BACKGROUND: Exophiala (Wangiella) dermatitidis is a clinically relevant black yeast. Although E. dermatitidis rarely causes human infection, it can cause superficial and deep-seated infections, and cutaneous and subcutaneous diseases. Cases of fungemia and central line-associated bloodstream infections due to E. dermatitidis are extremely uncommon, and their clinical manifestations and prognosis are still not well-known. Herein, we report a case of central line-associated bloodstream infections in a patient with cancer. These infections were caused by melanized yeast that was finally identified as E. dermatitidis via internal transcribed spacer sequencing and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. CASE PRESENTATION: A 75-year-old man with thoracic esophageal cancer and early gastric cancer presented with a 1-day history of fever during his hospitalization at our hospital. A central venous port was placed in the patient for total parenteral nutrition. Two E. dermatitidis isolates were recovered from two blood samples drawn at different times from a peripheral vein and this central venous port. The isolate was identified as E. dermatitidis by internal transcribed spacer sequencing and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The central venous port was removed, and the patient was administered micafungin and voriconazole. Although the minimum inhibitory concentrations of E. dermatitidis for voriconazole and minimum effective concentrations for micafungin were 2 µg/mL and 4 µg/m, respectively, the bacteremia was successfully treated. CONCLUSIONS: Although no clear treatment guidelines have been proposed for E. dermatitidis infections, immediate removal of central venous catheters is the key to improving central line-associated bloodstream infections.


Assuntos
Bacteriemia , Exophiala , Neoplasias , Idoso , Exophiala/genética , Humanos , Masculino , Neoplasias/complicações , Voriconazol
10.
Biosci Biotechnol Biochem ; 85(7): 1675-1685, 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-33930112

RESUMO

The fungus Exophiala jeanselmei strain KUFI-6N produces a unique cycloalkanone monooxygenase (ExCAMO) that displays an uncommon substrate spectrum of Baeyer-Villiger oxidation of 4-10-membered ring ketones. In this study, we aimed to identify and sequence the gene encoding ExCAMO from KUFI-6N and overexpress the gene in Escherichia coli. We found that the primary structure of ExCAMO is most closely related to the cycloalkanone monooxygenase from Cylindrocarpon radicicola ATCC 11011, with 54.2% amino acid identity. ExCAMO was functionally expressed in E. coli and its substrate spectrum and kinetic parameters were investigated. Substrate profiling indicated that ExCAMO is unusual among known Baeyer-Villiger monooxygenases owing to its ability to accept a variety of substrates, including C4-C12 membered ring ketones. ExCAMO has high affinity and catalytic efficiency toward cycloalkanones, the highest being toward cyclohexanone. Five other genes encoding Baeyer-Villiger monooxygenases were also cloned and expressed in E. coli.


Assuntos
Exophiala/enzimologia , Oxigenases de Função Mista/genética , Clonagem Molecular , Estabilidade Enzimática , Escherichia coli/genética , Cinética , Oxigenases de Função Mista/química , Oxigenases de Função Mista/metabolismo , Peso Molecular , Especificidade por Substrato , Temperatura
11.
Rev. iberoam. micol ; 38(1): 12-15, ene.-mar. 2021. tab, ilus
Artigo em Inglês | IBECS | ID: ibc-202389

RESUMO

BACKGROUND: Exophiala dermatitidis is a dematiaceous fungus known to cause superficial, subcutaneous, cutaneous and deep seated infections, and rarely central line associated bloodstream infection (CLABSI). A case of CLABSI due to E. dermatitidis in an infant is described. CASE REPORT: Clinical and laboratory data were extracted from patient's chart and laboratory records. The isolate was identified as E. dermatitidis by phenotypic characterization and sequencing of the ITS and LSU regions of the ribosomal DNA. Medline search was done to review all cases of CLABSI due to E. dermatitidis. Among the azoles tested, posaconazole (0.06mg/l), voriconazole (0.03mg/l) and itraconazole (0.03mg/l) showed very low MICs when compared to fluconazole (4mg/l). CONCLUSIONS: As we did not found in the literature any case of CLABSI due to E. dermatitidis in an infant, we report the first one. Sequencing is a mandatory method for accurately identifying this species. Prompt removal of the central line, followed by a treatment with amphotericin B or an azole, seems to be the most effective treatment


ANTECEDENTES: Exophiala dermatitidis es un hongo dematiáceo conocido por causar infecciones superficiales, subcutáneas, cutáneas y profundas, y rara vez infección del torrente sanguíneo asociada a catéter central (central line associated bloodstream infection [CLABSI]). Se describe un caso de CLABSI debido a E. dermatitidis en un bebé. CASO CLÍNICO: Los datos del paciente se extrajeron de la historia clínica y de los registros de laboratorio. El aislamiento se identificó como E. dermatitidis mediante caracterización fenotípica y la secuenciación de las regiones ITS y LSU del ADN ribosómico. Se realizó una búsqueda en Medline para revisar todos los casos de CLABSI debidos a E. dermatitidis. Entre los azoles evaluados, el posaconazol (0,06mg/l), el voriconazol (0,03mg/l) y el itraconazol (0,03mg/l) mostraron valores de MIC muy bajos en comparación con el fluconazol (4mg/l). CONCLUSIONES: Tras la revisión de todo lo publicado en la literatura, presentamos el primer caso de CLABSI debido a E. dermatitidis en un lactante. La secuenciación es necesaria para identificar con precisión esta especie. La retirada inmediata del catéter venoso central seguida de un tratamiento con anfotericina B o un azol es el tratamiento más efectivo


Assuntos
Humanos , Feminino , Lactente , Exophiala/isolamento & purificação , Infecções Relacionadas a Cateter/etiologia , Feoifomicose/complicações , Fungemia/microbiologia , Infecções Relacionadas a Cateter/terapia , DNA Ribossômico/análise , Azóis/administração & dosagem , Fluconazol/administração & dosagem , Cateterismo Venoso Central/efeitos adversos
12.
BMC Microbiol ; 21(1): 40, 2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-33546601

RESUMO

BACKGROUND: Melatonin (MT), ubiquitous in almost all organisms, functions as a free radical scavenger. Despite several reports on its role as an antioxidant in animals, plants, and some microorganisms, extensive studies in filamentous fungi are limited. Based upon the role of melatonin as an antioxidant, we investigated its role in heavy metal-induced stress tolerance in Exophiala pisciphila, a dark septate endophyte (DSE), by studying the underlying mechanisms in alleviating oxidative stress and reducing heavy metal accumulation. RESULTS: A significant decrease in malondialdehyde (MDA) and oxygen free radical (OFR) in E. pisciphila was recorded under Cd, Zn, and Pb stresses as compared to the control. Pretreatment of E. pisciphila with 200.0 µM exogenous melatonin significantly increased the activity of superoxide dismutase (SOD) under Zn and Pb stresses. Pretreatment with 200.0 µM melatonin also lowered Cd, Zn, and Pb concentrations significantly. Melatonin production was enhanced by Cd, Cu, and Zn after 2 d, and melatonin biosynthetic enzyme genes, E. pisciphila tryptophan decarboxylase (EpTDC1) and serotonin N-acetyltransferase (EpSNAT1), were transcriptionally upregulated. The overexpression of EpTDC1 and N-acetylserotonin O-methyltransferase (EpASMT1) in Escherichia coli and Arabidopsis thaliana enhanced its heavy metal-induced stress tolerance. The overexpression of EpTDC1 and EpASMT1 reduced the Cd accumulation in the whole A. thaliana plants, especially in the roots. CONCLUSIONS: Melatonin conferred heavy metal-induced stress tolerance by alleviating oxidative stress, activating antioxidant enzyme SOD, and reducing heavy metal accumulation in E. pisciphila. Melatonin biosynthetic enzyme genes of E. pisciphila also played key roles in limiting excessive heavy metal accumulation in A. thaliana. These findings can be extended to understand the role of melatonin in other DSEs associated with economically important plants and help develop new strategies in sustainable agriculture practice where plants can grow in soils contaminated with heavy metals.


Assuntos
Exophiala/efeitos dos fármacos , Exophiala/metabolismo , Melatonina/farmacologia , Metais Pesados/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/farmacologia , Vias Biossintéticas/genética , Exophiala/genética , Melatonina/biossíntese , Melatonina/genética , Estresse Oxidativo/genética , Poluentes do Solo
13.
J Mycol Med ; 31(1): 101105, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33422739

RESUMO

Chromoblastomycosis is a subcutaneous, chronic, granulomatous mycosis that occurs more frequently in tropical and subtropical countries. Herein, we describe a case of a 90-year-old female patient with diagnosis of chromoblastomycosis by Exophiala jeanselmei with a 22-year evolution who developed a squamous cell carcinoma. In the meantime, She underwent two misdiagnoses and an unnecessary operation. This case is also the fifth case of E. jeanselmei caused CBM in history.


Assuntos
Carcinoma de Células Escamosas/microbiologia , Cromoblastomicose/complicações , Cromoblastomicose/diagnóstico , Exophiala/patogenicidade , Idoso de 80 Anos ou mais , Antifúngicos/uso terapêutico , Cromoblastomicose/tratamento farmacológico , Cromoblastomicose/microbiologia , Exophiala/efeitos dos fármacos , Feminino , Humanos
14.
Perit Dial Int ; 41(3): 333-336, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32783526

RESUMO

We report the first case of peritoneal dialysis (PD) patients with peritonitis from Hortaea werneckii, a halotolerant black yeast-like fungus. The pathogen was confirmed by nucleotide sequences of internal transcribed spacer regions of the ribosomal RNA gene. A potential cause of this infection was tinea nigra on the patient's palm. Therefore, gloving might be advised during PD bag exchange in patients or caregivers who have an obvious lesion of the palm.


Assuntos
Exophiala , Diálise Peritoneal , Peritonite , Tinha , Humanos , Diálise Peritoneal/efeitos adversos , Peritonite/etiologia
15.
Environ Microbiol ; 23(7): 3627-3645, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33078510

RESUMO

Fungi have been observed to exhibit resistance to high levels of ionizing radiation despite sharing most DNA repair mechanisms with other eukaryotes. Radioresistance, in fact, is such a common feature in fungi that it is difficult to identify species that exhibit widely different radiosensitivities, which in turn has hampered the identification of genetic elements responsible for this resistance phenotype. Due to the inherent mutagenic properties of radiation exposure, however, this can be addressed through adaptive laboratory evolution for increased ionizing radiation resistance. Here, using the black yeast Exophiala dermatitidis, we demonstrate that resistance to γ-radiation can be greatly increased through repeated rounds of irradiation and outgrowth. Moreover, we find that the small genome size of fungi situates them as a relatively simple functional genomics platform for identification of mutations associated with ionizing radiation resistance. This enabled the identification of genetic mutations in genes encoding proteins with a broad range of functions from 10 evolved strains. Specifically, we find that greatly increased resistance to γ-radiation is achieved in E. dermatitidis through disruption of the non-homologous end-joining pathway, with three individual evolutionary paths converging to abolish this DNA repair process. This result suggests that non-homologous end-joining, even in haploid cells where homologous chromosomes are not present during much of the cell cycle, is an impediment to repair of radiation-induced lesions in this organism, and that the relative levels of homologous and non-homologous repair in a given fungal species may play a major role in its radiation resistance.


Assuntos
Exophiala , Radiação Ionizante , Reparo do DNA/genética , Tolerância a Radiação/genética
16.
Rev Iberoam Micol ; 38(1): 12-15, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33279387

RESUMO

BACKGROUND: Exophiala dermatitidis is a dematiaceous fungus known to cause superficial, subcutaneous, cutaneous and deep seated infections, and rarely central line associated bloodstream infection (CLABSI). A case of CLABSI due to E. dermatitidis in an infant is described. CASE REPORT: Clinical and laboratory data were extracted from patient's chart and laboratory records. The isolate was identified as E. dermatitidis by phenotypic characterization and sequencing of the ITS and LSU regions of the ribosomal DNA. Medline search was done to review all cases of CLABSI due to E. dermatitidis. Among the azoles tested, posaconazole (0.06mg/l), voriconazole (0.03mg/l) and itraconazole (0.03mg/l) showed very low MICs when compared to fluconazole (4mg/l) CONCLUSIONS: As we did not found in the literature any case of CLABSI due to E. dermatitidis in an infant, we report the first one. Sequencing is a mandatory method for accurately identifying this species. Prompt removal of the central line, followed by a treatment with amphotericin B or an azole, seems to be the most effective treatment.


Assuntos
Exophiala , Feoifomicose , Sepse , Antifúngicos/uso terapêutico , Exophiala/genética , Humanos , Lactente , Feoifomicose/diagnóstico , Feoifomicose/tratamento farmacológico , Sepse/tratamento farmacológico
17.
Chembiochem ; 22(7): 1232-1242, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33242357

RESUMO

Amine transaminases (ATAs) are used to synthesize enantiomerically pure amines, which are building blocks for pharmaceuticals and agrochemicals. R-selective ATAs belong to the fold type IV PLP-dependent enzymes, and different sequence-, structure- and substrate scope-based features have been identified in the past decade. However, our knowledge is still restricted due to the limited number of characterized (R)-ATAs, with additional bias towards fungal origin. We aimed to expand the toolbox of (R)-ATAs and contribute to the understanding of this enzyme subfamily. We identified and characterized four new (R)-ATAs. The ATA from Exophiala sideris contains a motif characteristic for d-ATAs, which was previously believed to be a disqualifying factor for (R)-ATA activity. The crystal structure of the ATA from Shinella is the first from a Gram-negative bacterium. The ATAs from Pseudonocardia acaciae and Tetrasphaera japonica are the first characterized (R)-ATAs with a shortened/missing N-terminal helix. The active-site charges vary significantly between the new and known ATAs, correlating with their diverging substrate scope.


Assuntos
Transaminases/metabolismo , Actinobacteria/enzimologia , Sequência de Aminoácidos , Sítios de Ligação , Biocatálise , Domínio Catalítico , Escherichia coli/metabolismo , Exophiala/enzimologia , Simulação de Acoplamento Molecular , Rhizobiaceae/enzimologia , Alinhamento de Sequência , Estereoisomerismo , Especificidade por Substrato , Transaminases/química , Transaminases/genética
18.
Nat Prod Res ; 35(10): 1573-1581, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-31170816

RESUMO

Chemical characterization of ethyl acetate extract of Exophiala sp. has afforded the isolation of three compounds including a new isocoumarin named exophiarin (1). Exophiala sp. was obtained from the soil containing dumped organic waste (litter). Initially, LC-UV-MS analysis of the extract of Exophiala sp. revealed the presence of a new compound having molecular weight 438 (1) and previously reported TPI-2 and TPI-5. The novelty was established using advanced database search comprising of biological source, molecular weight and UV profile. 1D, 2D NMR and HRMS data have been used for structure elucidation. Exophiarin with TPI-2 and TPI-5 have displayed moderate improvement in glucose uptake activity when tested in rat skeletal muscle cell line L6.


Assuntos
Exophiala/química , Hipoglicemiantes/farmacologia , Isocumarinas/farmacologia , Animais , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Isocumarinas/química , Isocumarinas/isolamento & purificação , Camundongos , Peso Molecular , Filogenia , Espectroscopia de Prótons por Ressonância Magnética
19.
Nat Prod Res ; 35(15): 2598-2601, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31674836

RESUMO

Three pregnene steroids, two of them new, were isolated from ethyl-acetate partition of liquid-cultivation of the extremophyle fungus Exophiala oligosperma, found in a pH 1.5 hydrochloric acid aqueous solution. Spectroscopic studies using NMR and HRMS, allowed the identification of the molecular structures of both Δ8,9-pregnenes, still not described in the literature.


Assuntos
Exophiala/química , Extremófilos , Pregnenos/química , Esteroides/química , Fungos , Pregnenos/isolamento & purificação , Esteroides/isolamento & purificação
20.
Front Cell Infect Microbiol ; 10: 576975, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194816

RESUMO

Infections of Exophiala dermatitidis are often chronic and recalcitrant. Combination therapies with novel compounds and azoles could be an effective solution. Previously, we have demonstrated that pyrvinium pamoate exerted antifungal activity alone and favorable synergy with azoles against planktonic E. dermatitidis. Herein, the underlying antifungal mode of action were investigated. Pyrvinium alone showed sessile MIC50 (SMIC50) of 8->16 µg/ml against E. dermatitidis biofilms. However, synergism of PP with itraconazole, voriconazole, and posaconazole were observed against 16 (88.9%), 9 (50%), and 13 (72.2%) strains of E. dermatitidis biofilms. In accordance with in vitro susceptibilities, pyrvinium alone at concentration of 2 µg/ml resulted in significant growth restriction of planktonic E. dermatitidis. Pyrvinium alone resulted in reduction of biofilm formation. Higher concentration of pyrvinium was associate with more progressive reduction of biofilm mass. The in vivo activity of pyrvinium alone and combined with azoles was evaluated using Galleria mellonella model. Pyrvinium alone significantly improved the survival rate of larvae (P < 0.0001). The combination of pyrvinium and voriconazole or posaconazole acted synergistically in vivo (P < 0.05). Fungal burden determination revealed significant reduction of numbers of colony forming unit (CFU) in larvae treated with pyrvinium-itraconazole and pyrvinium-posaconazole compared to itraconazole or posaconazole alone group, respectively. The effect of pyrvinium on apoptosis, expression of TOR and HSP90, and drug efflux reversal were evaluated by PI/Annexin V staining, Real-Time Quantitative PCR and Rhodamine 6G assay, respectively. Pyrvinium alone or combined with azoles significantly (P < 0.05) increased late apoptosis or necrosis of E. dermatitidis cells. Pyrvinium combined with posaconazole significantly decreased the expression of TOR and Hsp90 compared to posaconazole alone group (P < 0.05). Pyrvinium resulted in significant (P < 0.05) decrease of the efflux of Rhodamine 6G. These findings suggested pyrvinium could be a promising synergist with azoles. The underlying mechanisms could be explained by inducing apoptosis/necrosis, inhibition of drug efflux pumps, and signaling pathways related with stress response and growth control.


Assuntos
Azóis , Exophiala , Antifúngicos/farmacologia , Azóis/farmacologia , Testes de Sensibilidade Microbiana , Compostos de Pirvínio
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...