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1.
Rev Iberoam Micol ; 37(2): 65-67, 2020.
Article in Spanish | MEDLINE | ID: mdl-32376274

ABSTRACT

BACKGROUND: Schizophyllum commune is a basidiomycete fungus which is widely distributed in nature. Its role as responsible for disease in humans is not well known, partly due to its difficult identification. The incorporation of mass spectrometry techniques (MALDI-TOF) and molecular biology to the laboratories has allowed the description of a greater number of cases. CASE REPORT: In this paper, we present two cases in which S. commune was identified as the causative agent of disease: in the first case an immunocompetent patient suffered from chronic rhinosinusitis, and in the second one a sphenoid sinus infection was diagnosed in an immunocompromised patient. In both cases, S. commune was isolated. Its identification was possible by means of MALDI-TOF and this was confirmed in both patients by amplification and sequencing of the ITS region. CONCLUSIONS: In conclusion, S. commune should be considered a potential causative agent of fungal disease. Currently, MALDI-TOF and sequencing techniques are necessary for its identification.


Subject(s)
Maxillary Sinusitis/microbiology , Mycoses/microbiology , Schizophyllum/isolation & purification , Sphenoid Sinusitis/microbiology , Adult , Aged , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Drug Resistance, Fungal , Foreign Bodies/complications , Humans , Male , Mucocele/complications , Schizophyllum/drug effects , Schizophyllum/pathogenicity
2.
BMC Microbiol ; 20(1): 139, 2020 05 29.
Article in English | MEDLINE | ID: mdl-32471364

ABSTRACT

BACKGROUND: In the last few decades, considerable attention has been paid to fungal endophytes as biocontrol agents, however little is known about their mode of action. This study aimed to investigate the toxic effects of an endophytic fungus Schizophyllum commune by analyzing activities of antioxidant and detoxifying enzymes as well as morphology of haemocytes using Spodoptera litura as a model. RESULTS: Ethyl acetate extract of S. commune was fed to the larvae of S. litura using the artificial diet having 276.54 µg/ml (LC50 of fungus) concentration for different time durations. Exposed groups revealed significant (p ≤ 0.05) increase in the activities of various enzymes viz. Catalase, Ascorbate peroxidase, Superoxide dismutase, Glutathione-S-Transferase. Furthermore, haemocytes showed various deformities like breakage in the cell membrane, cytoplasmic leakage and appearance of strumae in the treated larvae. A drastic reduction in the percentage of normal haemocytes was recorded in the treated groups with respect to control. CONCLUSION: The study provides important information regarding the oxidative stress causing and immunosuppressant potential of S. commune against S. litura and its considerable potential for incorporation in pest management programs.


Subject(s)
Biological Products/pharmacology , Immunosuppressive Agents/pharmacology , Schizophyllum/pathogenicity , Spodoptera/microbiology , Animals , Biological Products/isolation & purification , Enzymes/genetics , Gene Expression Regulation, Enzymologic/drug effects , Hemocytes/drug effects , Immunosuppressive Agents/isolation & purification , Insect Proteins/genetics , Oxidative Stress , Pest Control , Schizophyllum/chemistry , Spodoptera/immunology
3.
J Infect Chemother ; 26(5): 506-509, 2020 May.
Article in English | MEDLINE | ID: mdl-32146107

ABSTRACT

Schizophyllum commune, a basidiomycete fungus, is a quite rare cause of invasive sinusitis for which no standard treatment has yet been established. We report herein a 59-year-old woman who developed S. commune rhinosinusitis after remission induction chemotherapy for her acute myeloid leukemia. No causative microorganisms were identified in the sinus lavage fluid culture, whereas nucleotide sequencing of the internal transcribed spacer region using endoscopic sinus biopsy specimen could confirm the pathogen as S. commune. Liposomal amphotericin B and voriconazole (VRCZ) treatment ameliorated both her clinical symptoms and laboratory findings. The patient was successfully treated with allogeneic stem cell transplantation, under continuous VRCZ administration, without aggravation of S. commune sinusitis. Molecular diagnosis and prompt intervention with suitable antifungal drugs may be crucial to manage this rare infectious complication.


Subject(s)
Hematopoietic Stem Cell Transplantation/methods , Invasive Fungal Infections/complications , Leukemia, Myeloid, Acute/therapy , Rhinitis/microbiology , Schizophyllum/pathogenicity , Sinusitis/microbiology , Amphotericin B/therapeutic use , Antifungal Agents/therapeutic use , Drug Therapy, Combination , Female , Humans , Invasive Fungal Infections/diagnosis , Invasive Fungal Infections/drug therapy , Invasive Fungal Infections/microbiology , Leukemia, Myeloid, Acute/complications , Middle Aged , Molecular Diagnostic Techniques , Rhinitis/complications , Rhinitis/diagnosis , Rhinitis/drug therapy , Schizophyllum/genetics , Schizophyllum/isolation & purification , Sinusitis/complications , Sinusitis/diagnosis , Sinusitis/drug therapy , Transplantation, Homologous , Treatment Outcome , Voriconazole/therapeutic use
4.
Transpl Infect Dis ; 22(1): e13205, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31674700

ABSTRACT

Sinusitis is a serious infectious complication of allogeneic hematopoietic stem cell transplantation. Schizophyllum commune (S commune) is a common basidiomycete fungus that is rarely involved in human disease. We report herein a case of S commune sinusitis after allogeneic bone marrow transplantation. A 66-year-old man with myelodysplastic syndrome underwent allogeneic bone marrow transplantation and developed maxillary and ethmoid sinusitis. The sinusitis did not improve with liposomal amphotericin B after neutrophil engraftment, so we considered that surgical intervention was needed for the recovery of sinusitis. Endoscopic sinus surgery was performed. In the debridement tissue of paranasal mucosa, filamentous fungal elements were observed. Moreover, genetic analysis of the tissue revealed the presence of S commune. Schizophyllum commune should be recognized as a fungal pathogen that causes sinusitis after allogeneic hematopoietic stem cell transplantation. This case suggests the effectiveness of prompt surgical intervention with liposomal amphotericin B treatment for S commune sinusitis and the usefulness of genetic diagnosis for cases under antifungal treatment. (160 words).


Subject(s)
Bone Marrow Transplantation/adverse effects , Mycoses/etiology , Myelodysplastic Syndromes/complications , Sinusitis/microbiology , Aged , Amphotericin B/therapeutic use , Antifungal Agents/therapeutic use , Endoscopy , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Male , Mycoses/diagnosis , Mycoses/drug therapy , Myelodysplastic Syndromes/therapy , Schizophyllum/genetics , Schizophyllum/pathogenicity , Sinusitis/surgery
5.
J Mycol Med ; 29(4): 365-371, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31543381

ABSTRACT

Schizophyllumcommune is an environmental basidiomycetous fungus, causing occasional, predominantly respiratory, infections in humans. Although S. commune is considered an emerging pathogen, some authors pointed out the possibility that the increase in the diagnosed cases may be also due to recent advances in diagnostic technologies now allowing a more prompt and precise identification at the species level. Here we describe the first Italian case of chronic non-invasive fungal rhinosinusitis due to S. commune in an immunocompetent subject and update the literature review on S. commune sinusitis published between 2012-2019. A timely diagnosis is important to avoid local and systemic complications due to infection with this fungus. In our case, prompt identification at species level was only possible with the use of MALDI-TOF mass spectrometry and confirmed by sequence analysis of ribosomal DNA ITS regions, due to the difficulty in achieving a correct and rapid identification using routine morphological analysis.


Subject(s)
Mycoses/diagnosis , Schizophyllum/isolation & purification , Sinusitis/diagnosis , Sinusitis/microbiology , Chronic Disease , Face/diagnostic imaging , Face/microbiology , Female , Humans , Immunocompetence , Italy , Middle Aged , Mycoses/microbiology , Schizophyllum/genetics , Schizophyllum/pathogenicity , Sequence Analysis, DNA , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Tomography, X-Ray Computed
7.
Mol Biol Rep ; 46(4): 3877-3886, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31016617

ABSTRACT

Schizophyllum commune is a well-known mushroom forming fungi which is an edible one due to its nutritive value. It exhibits a special wood degrading mechanism to grow in decay matters by releasing a series of enzymes. These enzymes might make them an opportunistic pathogen which has been reported to infect various animals and human beings too. Although these fungi were identified as human and animal pathogens, their mechanisms of pathogenesis and the key virulence factors involved in disease establishment are not known. In this study, we reported this fungal infection in freshwater fish for the first time and its morphological features. Further, we employed RNA-seq technique to identify the major virulence factors involved in the pathogenesis in fish and the network of interaction between the identified virulence factors were analysed. Also, we confirmed the virulence roles of this fungus during infection by qRT-PCR analysis. This study emphasizes the virulence nature of the common mushroom forming food fungus and the involvement of enzymes such as phosphoinositide phospholipase C, hexosaminidase and few toxins such as pesticidal and insecticidal crystal proteins which opened a new avenue in the virulence nature of edible mushrooms.


Subject(s)
Schizophyllum/genetics , Schizophyllum/metabolism , Animals , Fishes/microbiology , Fungal Proteins/genetics , Gene Expression Profiling/methods , Glycoside Hydrolases , Mycoses/genetics , Mycoses/pathology , Opportunistic Infections/genetics , Opportunistic Infections/metabolism , Phosphoinositide Phospholipase C , Schizophyllum/pathogenicity , Transcriptome/genetics , Virulence , Virulence Factors/metabolism
9.
Clin Lab ; 61(11): 1799-801, 2015.
Article in English | MEDLINE | ID: mdl-26732008

ABSTRACT

Schizophyllum commune infections have been rarely reported. Here we reported a rare case of sinusitis in an acute myelocytic leukemia patient, who was co-infected by Escherichia coli, Stenotrophomonas maltophilia, and basidiomycetous fungi (Schizophyllum commune) in sinuses. Considering the in vitro and in vivo anti-fungal activity of voriconazole, it might be a good option to treat Schizophyllum commune infections when antifungal susceptibility testing is not available. When severe side effects occur, amphotericin B or itraconazole might be subsequent choice.


Subject(s)
Escherichia coli/pathogenicity , Leukemia, Myeloid, Acute/complications , Mycoses/complications , Schizophyllum/pathogenicity , Sinusitis/microbiology , Adult , Female , Humans , Mycoses/microbiology , Sinusitis/complications , Sinusitis/diagnostic imaging , Tomography, X-Ray Computed
10.
Mycopathologia ; 177(1-2): 103-10, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24318775

ABSTRACT

Schizophillum commune is an environmental fungus rarely causing human infections of diverse nature. Sinusitis occurs in immunocompromised persons and seldom in healthy subjects. Though easily isolated, the lack of awareness of its virulence is a bottleneck in the diagnosis of this infection. We report the first case of S. commune sinusitis with nasal polyps in an immunocompetent male from the sub-Himalayan region. The computerized tomography scan findings established the clinical diagnosis, and causative agent was confirmed as S. commune. A white, woolly mold with septate, hyaline hyphae and characteristic spicules but unclamped connections suggested a monokaryotic isolate. Patient was treated successfully with fiberoptic endoscopic sinus surgery, and no antifungal therapy was instituted. There was no recurrence at review after 1 year.


Subject(s)
Mycoses/microbiology , Nasal Polyps/microbiology , Schizophyllum/pathogenicity , Sinusitis/microbiology , Adult , Aged , Endoscopy , Female , Humans , Hyphae/physiology , Male , Middle Aged , Mycological Typing Techniques , Mycoses/diagnosis , Mycoses/surgery , Nasal Polyps/surgery , Sinusitis/diagnosis , Sinusitis/surgery , Tomography, X-Ray Computed , Young Adult
11.
Mycoses ; 56(1): 1-10, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22524529

ABSTRACT

We report Schizophyllum commune as the aetiological agent of one case each of allergic broncho-pulmonary mycosis (ABPM) and pulmonary fungal ball, and present a literature review. The fungus was characterised by clamp connections, hyphal spicules, and formation of basidiocarps with basidiospores. The phenotypic identification was confirmed by sequencing of the ITS region. To-date, ABPM and pulmonary fungal ball to S. commune have been reported exclusively from Japan and North America respectively. Of the 71 globally reported cases due to S. commune, 45 (63%) were bronchopulmonary, 22 (31%) sinusitis and 4 extrapulmonary. Taken together, cases of bronchopulmonary disease and sinusitis numbered 67 (94%), indicating the respiratory tract as the primary target of disease. Concerning the country-wise distribution, Japan topped the list with 33 cases (46%), followed by Iran - 7 cases (10%), U.S.A. - 6 cases (9%), and a lower prevalence of 1.4-6% for the remaining 12 countries. The preponderance of the disease in Japan may be attributed to its greater awareness vis-à-vis that in other countries rather than to any geographical/climatic factors. We believe that the burden of S. commune-incited disease is currently underestimated, warranting comprehensive prospective studies to determine its prevalence.


Subject(s)
Lung Diseases, Fungal/microbiology , Schizophyllum/isolation & purification , Adult , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunodiffusion , Immunoglobulin E/blood , Male , Microbial Sensitivity Tests , Schizophyllum/drug effects , Schizophyllum/pathogenicity , Skin Tests
12.
Rhinology ; 47(2): 217-21, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19593982

ABSTRACT

Schizophillum commune (S. commune) is a rare type of basidiomycetous fungus that has being reported as a cause of allergic fungal rhinosinusitis (AFRS), invasive type of fungal sinusitis and allergic bronchopulmonary mycosis (ABPM). However, it is believed that S. commune was often misdiagnosed to Aspergillus sp. We report a case of bilateral nasal polyps and maxillary, ethmoidal and sphenoidal involvement within the context of S. commune and Aspergillus niger associated AFRS. Our patient was suffering from a chronic disease with periods of remission and exacerbation and was treated successfully by a combination of surgical and antifungal treatment. In our experience, S. commune may be found frequently in patients with AFRS. AFRS, including the S. commune-associated type, usually runs a prolonged course and can affect any paranasal sinus. Surgical treatment alone is not sufficient and must be combined with medical treatment.


Subject(s)
Aspergillus niger/pathogenicity , Mycoses/microbiology , Rhinitis/microbiology , Schizophyllum/pathogenicity , Sinusitis/microbiology , Antifungal Agents/therapeutic use , Aspergillus niger/isolation & purification , Combined Modality Therapy , Endoscopy , Female , Humans , Middle Aged , Mycoses/diagnostic imaging , Mycoses/drug therapy , Mycoses/surgery , Rhinitis/diagnostic imaging , Rhinitis/drug therapy , Rhinitis/surgery , Schizophyllum/isolation & purification , Sinusitis/diagnostic imaging , Sinusitis/drug therapy , Sinusitis/surgery , Tomography, X-Ray Computed
13.
J Vet Med Sci ; 70(11): 1257-9, 2008 Nov.
Article in English | MEDLINE | ID: mdl-19057147

ABSTRACT

A six-year-old female Labrador retriever dog was suffering from osteomyelitis in her hindlimb. A puncture wound caused by a rotted bamboo stick was presumed as the source of infection. The dog suffered from pre-existing aortic stenosis, but otherwise exhibited no significant abnormality in her systemic conditions excluding claudication of the left hindlimb. The results of cytology and pathological examinations of biopsy samples revealed the diagnosis of mycotic osteomyelitis in this dog. Mycological and DNA tests showed the pathogen as the mushroom Schizophyllum commune. Antibiotic sensitivity testing also revealed susceptibility to itraconazole, which was used to successfully treat the dog. This is a rare case of canine basidiomycosis with S. commune as the etiologic agent.


Subject(s)
Antifungal Agents/therapeutic use , Dog Diseases/microbiology , Itraconazole/therapeutic use , Mycoses/veterinary , Osteomyelitis/veterinary , Schizophyllum/pathogenicity , Animals , Bone Resorption/microbiology , Bone Resorption/veterinary , DNA Primers , DNA, Fungal/genetics , Dog Diseases/drug therapy , Dog Diseases/physiopathology , Dogs , Female , Mycoses/drug therapy , Mycoses/physiopathology , Osteomyelitis/drug therapy , Osteomyelitis/physiopathology , Polymerase Chain Reaction , Schizophyllum/genetics , Schizophyllum/isolation & purification
14.
Nihon Kokyuki Gakkai Zasshi ; 41(3): 233-6, 2003 Mar.
Article in Japanese | MEDLINE | ID: mdl-12772607

ABSTRACT

We report on two patients, a 27-year-old and a 33-year-old woman, with allergic bronchopulmonary mycosis (ABPM) caused by the basidiomycetous fungus Schizophyllum commune (S. commune). Each patient had bronchial asthma. Both were admitted to our institution for further examination of cough, sputum, and abnormal chest shadows. ABPM was strongly suspected, because they showed eosinophilia in both peripheral blood and sputum, and increased serum IgE levels. A mold was isolated from their sputum, but identification was not possible. Systemic corticosteroid therapy relieved their symptoms and chest abnormal shadows. Later, S. commune, a basidiomycetous fungus, was detected from further examination of their sputum cultures, and serum anti-S. commune IgG was elevated. Finally, both cases were diagnosed as ABPM caused by S. commune. It is reported that this syndrome typically develops in women in middle age, but our patients were young women. It is important to take into account the possibility of ABPM caused by S. commune even in young patients when Aspergillus species are not isolated.


Subject(s)
Asthma/microbiology , Hypersensitivity/microbiology , Lung Diseases, Fungal/microbiology , Schizophyllum/pathogenicity , Adult , Age Factors , Asthma/drug therapy , Female , Humans , Hypersensitivity/diagnosis , Hypersensitivity/drug therapy , Lung Diseases, Fungal/diagnosis , Lung Diseases, Fungal/drug therapy , Prednisolone/administration & dosage , Schizophyllum/isolation & purification , Sputum/microbiology , Treatment Outcome
15.
Nihon Ishinkin Gakkai Zasshi ; 40(3): 175-81, 1999.
Article in Japanese | MEDLINE | ID: mdl-10423513

ABSTRACT

Infections caused by Schizophyllum commune have recently been on the increase. We analyzed cases in which this fungus was isolated from clinical samples from 1991 to 1995. Regular morphological methods were first employed in the identification of S. commune, and when necessary, mating was made with a known S. commune isolate. IgG antibodies against S. commune in the patients' serum were determined by the ELISA method. Profiles of the cases were analyzed and the English-language medical literature was reviewed. S. commune was isolated from 12 patients. Eighty three percent of the patients were female, most of which presented with allergy-related pulmonary diseases, i. e. allergic bronchopulmonary mycosis or mucoid impaction of bronchi. IgG antibodies were detectable in nine of eleven patients examined (82%). Fifty eight percent of the isolates were monokaryotic, and therefore, unidentifiable by regular morphological methods. In contrast, analysis of the English literature disclosed that sinusitis is the most common form of infection, and that hyphal invasion into the tissue was seen in 50% of reported cases. Our study shows that S. commune should be regarded as a pathogenic fungus, and is infecting humans much more frequently than previously assumed. Further investigation is warranted.


Subject(s)
Lung Diseases, Fungal/microbiology , Schizophyllum/isolation & purification , Adolescent , Adult , Age Factors , Aged , Antibodies, Fungal/analysis , Bronchi/microbiology , Female , Humans , Immunoglobulin G/analysis , Japan/epidemiology , Lung Diseases, Fungal/diagnosis , Lung Diseases, Fungal/epidemiology , Male , Middle Aged , Schizophyllum/immunology , Schizophyllum/pathogenicity , Sex Factors
18.
Nihon Kyobu Shikkan Gakkai Zasshi ; 34(7): 804-9, 1996 Jul.
Article in Japanese | MEDLINE | ID: mdl-8810763

ABSTRACT

In December 1989, a 72-year-old woman was hospitalized with atelectasis in the left lower lobe. The atelectasis resolved after bronchoscopic removal of impacted mucous plugs. Histopathological examination showed pulmonary mycosis. Microscopy suggested that a species of Aspergillus was responsible, but no definite diagnosis was made. After treatment with flucytosine and nebulized amphotericin, the patient's condition improved and she was discharged. In the middle of August 1994, she visited a local hospital complaining of fatigue. Eosinophilia (22%) was detected, and a few days later she visited that hospital again due to sudden dyspnea. A chest X-ray examination showed an abnormal shadow, and she was referred to our hospital. Atelectasis was seen in the left upper lobe. This finding, together with eosinophilia, suggested recurrence of pulmonary mycosis, and therefore bronchoscopy was performed. White mucous plugs obstructing the left upper lobe were observed and were bronchoscopically removed. Microscopical examination of the mucous plugs showed marked eosinophil infiltration and hyphae. Cultures of specimens obtained during bronchoscopy showed Schizophyllum commune, and allergic bronchopulmonary mycosis due to this microorganism was diagnosed. Identification of this microorganism as a cause of deep-seated pulmonary mycosis is very rare.


Subject(s)
Lung Diseases, Fungal/microbiology , Schizophyllum/isolation & purification , Aged , Female , Humans , Lung/microbiology , Lung/pathology , Lung Diseases, Fungal/diagnosis , Lung Diseases, Fungal/pathology , Schizophyllum/pathogenicity
19.
J Clin Microbiol ; 34(7): 1628-32, 1996 Jul.
Article in English | MEDLINE | ID: mdl-8784558

ABSTRACT

Despite the worldwide distribution and prevalence of Schizophyllum commune, an emerging basidiomycetous pathogen, human infections occur only rarely. We describe the first well-documented pulmonary infection caused by S. commune which disseminated to the brain of a 58-year-old patient undergoing empiric corticosteroid therapy. Magnetic resonance imaging scans revealed ring-enhancing masses. Histologic examination of biopsy tissue from lungs and brain showed hyaline, septate, branched hyphae with clamp connections. Cultures of the lung tissue grew S. commune, which produced numerous, characteristic flabelliform and medusoid fruiting bodies on Czapek's agar. The isolate was susceptible to amphotericin B (MIC, < 0.03 microgram/ml) and fluconazole (MIC, 8 micrograms/ml). Despite treatment with antifungal and antibacterial agents, the patient developed progressive pulmonary failure and bacterial sepsis and died.


Subject(s)
Brain Abscess/etiology , Mycoses/etiology , Schizophyllum/pathogenicity , Antifungal Agents/therapeutic use , Brain Abscess/diagnosis , Brain Abscess/microbiology , Fatal Outcome , Humans , Lung Diseases, Fungal/diagnosis , Lung Diseases, Fungal/etiology , Lung Diseases, Fungal/microbiology , Magnetic Resonance Imaging , Male , Middle Aged , Mycoses/diagnosis , Mycoses/microbiology , Schizophyllum/isolation & purification
20.
Clin Infect Dis ; 18(3): 305-9, 1994 Mar.
Article in English | MEDLINE | ID: mdl-8011808

ABSTRACT

We describe, to our knowledge, the first case of allergic bronchopulmonary mycosis (ABPM) caused by the basidiomycetous fungus Schizophyllum commune in an otherwise healthy woman. Bronchoscopic analysis repeatedly disclosed S. commune hyphae in the bronchi of the lingular lobe; these hyphae were originally misidentified as Aspergillus because the presence of clamp connections was overlooked. A lingular infiltrate with ectatic proximal bronchi, eosinophilia, an elevated serum level of IgE, and antibodies to S. commune supported the diagnosis. It is sometimes difficult to isolate and identify S. commune in clinical specimens, and hence only a limited number of cases of ABPM might have been correctly diagnosed in the past. We suspect, therefore, that some cases of ABPM caused by an allergic reaction to S. commune may be misdiagnosed as allergic bronchopulmonary aspergillosis or eosinophilic pneumonia of unknown origin. The significance of S. commune in allergic bronchopulmonary diseases is discussed.


Subject(s)
Hypersensitivity/etiology , Lung Diseases, Fungal/etiology , Schizophyllum/pathogenicity , Antibodies, Fungal/blood , Antigens, Fungal/isolation & purification , Bronchoalveolar Lavage Fluid/microbiology , Enzyme-Linked Immunosorbent Assay , Female , Humans , Hypersensitivity/diagnosis , Hypersensitivity/microbiology , Lung Diseases, Fungal/diagnosis , Lung Diseases, Fungal/microbiology , Middle Aged , Schizophyllum/immunology , Schizophyllum/isolation & purification
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