A new benzaldehyde from the coral-derived fungus Aspergillus terreus C23-3 and its anti-inflammatory effects via suppression of MAPK signaling pathway in RAW264.7 cells / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Marine fungi are important members of the marine microbiome, which have been paid growing attention by scientists in recent years. The secondary metabolites of marine fungi have been reported to contain rich and diverse compounds with novel structures (Chen et al., 2019). Aspergillus terreus, the higher level marine fungus of the Aspergillus genus (family of Trichocomaceae, order of Eurotiales, class of Eurotiomycetes, phylum of Ascomycota), is widely distributed in both sea and land. In our previous study, the coral-derived A. terreus strain C23-3 exhibited potential in producing other biologically active (with antioxidant, acetylcholinesterase inhibition, and anti-inflammatory activity) compounds like arylbutyrolactones, territrems, and isoflavones, and high sensitivity to the chemical regulation of secondary metabolism (Yang et al., 2019, 2020; Nie et al., 2020; Ma et al., 2021). Moreover, we have isolated two different benzaldehydes, including a benzaldehyde with a novel structure, from A. terreus C23-3 which was derived from Pectinia paeonia of Xuwen, Zhanjiang City, Guangdong Province, China.

Study on chemical constituents of sponge-associated Aspergillus terreus / 药学实践杂志

Objective To study the chemical constituents of Aspergillus terreus from sponge epiphytic fungal. Methods Sephadex LH-20 column chromatography, silica gel column chromatography and high performance liquid chroma-tography were used to separate and purify the compounds. The structures of compounds were identified by spectroscopic data. The α-glucosidase inhibitory activity and antioxidant activity of the compounds were tested by PNPG and DPPH methods, respectively. Results Eight compounds were isolated from Aspergillus terreus and identified as methyl-3,4,5-trimethoxy-2-(2-(nicotinamido) benzamido) benzoate (1), terrelumamide A (2), emeheterone (3), (8R,9S)-dihydroisoflavipucine (4), (8S,9S)-dihydroisoflavipucine (5), cyclo(S-Pro-S-Phe) (6), brevianamide F (7), terrein (8). Compound 3 showed strong inhibitory activity against α-glucosidase and the IC50 value was 14.28 μmol/L. Conclusion Compounds 3, 4, 5, and 7 were obtained from Aspergillus terreus for the first time.

Peptides and polyketides isolated from the marine sponge-derived fungus Aspergillus terreus SCSIO 41008 / 中国天然药物

Two new isomeric modified tripeptides, aspergillamides C and D (compounds 1 and 2), together with fifteen known compounds (compounds 3-17), were obtained from the marine sponge-derived fungus Aspergillus terreus SCSIO 41008. The structures of the new compounds, including absolute configurations, were determined by extensive analyses of spectroscopic data (NMR, MS, UV, and IR) and comparisons between the calculated and experimental electronic circular dichroism (ECD) spectra. Butyrolactone I (compound 11) exhibited strong inhibitory effects against Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB) with the IC being 5.11 ± 0.53 μmol·L, and acted as a noncompetitive inhibitor based on kinetic analysis.

Statistical optimization of kojic acid production by a UV-induced mutant strain of Aspergillus terreus

ABSTRACT The ability of four Aspergillus strains for biosynthesis of kojic acid was evaluated among which Aspergillus terreus represented the highest level (2.21 g/L) of kojic acid production. Improvement kojic acid production ability of A. terreus by random mutagenesis using different exposure time to ultraviolet light (5-40 min) was then performed to obtain a suitable mutant of kojic acid production (designated as C5-10, 7.63 g/L). Thereafter, design of experiment protocol was employed to find medium components (glucose, yeast extract, KH2PO4 (NH4)2SO4, and pH) influences on kojic acid production by the C5-10 mutant. A 25-1 fractional factorial design augmented to central composite design showed that glucose, yeast extract, and KH2PO4 were the most considerable factors within the tested levels (p < 0.05). The optimum medium composition for the kojic acid production by the C5-10 mutant was found to be glucose, 98.4 g/L; yeast extract, 1.0 g/L; and KH2PO4, 10.3 mM which was theoretically able to produce 120.2 g/L of kojic acid based on the obtained response surface model for medium optimization. Using these medium compositions an experimental maximum Kojic acid production (109.0 ± 10 g/L) was acquired which verified the efficiency of the applied method.

Presumably contaminated intravenous infusion-induced Aspergillus terreus endogenous endophthalmitis presenting with posterior hypopyon

A 36-year-old immunocompetent man developed endogenous endophthalmitis 1 week after intravenous fluid infusion in a rural setting. Large submacular abscess with posterior hypopyon warranted urgent vitrectomy which revealed Aspergillus terreus on fungal culture. Intravitreal and oral antifungals lead to resolution of inflammation with satisfactory anatomic outcome but poor visual outcome due to submacular scar.

Aspergillus terreus JF27 Promotes the Growth of Tomato Plants and Induces Resistance against Pseudomonas syringae pv. tomato

Certain beneficial microorganisms isolated from rhizosphere soil promote plant growth and induce resistance to a wide variety of plant pathogens. We obtained 49 fungal isolates from the rhizosphere soil of paprika plants, and selected 18 of these isolates that did not inhibit tomato seed germination for further investigation. Based on a seed germination assay, we selected four isolates for further plant tests. Treatment of seeds with isolate JF27 promoted plant growth in pot tests, and suppressed bacterial speck disease caused by Pseudomonas syringae pathovar (pv.) tomato DC3000. Furthermore, expression of the pathogenesis-related 1 (PR1) gene was higher in the leaves of tomato plants grown from seeds treated with JF27; expression remained at a consistently higher level than in the control plants for 12 h after pathogen infection. The phylogenetic analysis of a partial internal transcribed spacer sequence and the β-tubulin gene identified isolate JF27 as Aspergillus terreus. Taken together, these results suggest that A. terreus JF27 has potential as a growth promoter and could be used to control bacterial speck disease by inducing resistance in tomato plants.

Study on Identification of Lipid Metabolites of Endophytic Fungus Aspergillus terreus from Polygonum capitatum and Their Anti-multidrug Resistant Bacteria and Anti-inflammatory Effects / 中国药房

OBJECTIVE:To identify lipid metabolites of endophytic fungus Aspergillus terreus from Polygonum capitatum, and to investigate their anti-multidrug resistant bacteria and anti-inflammatory effects. METHODS:GC-MS was used to analyze and identify lipid metabolites of A. terreus. MIC of lipid metabolites and main composition to 10 strains of multidrug resistant bacteria (Klebsiella pneumoniae,Proteus common,Staphylococcus epidermidis,Escherichia coli,Staphylococcus aureus,Enterobacter cloacae,Pseudomonas aeruginosa,Proteus mirabilis,Enterococcus faecium and Acinetobacter baumanii) were determined by 96-well plate microdilution method. The spread plate method was used to determine MBC of samples to bacteria. LPS-induced RAW264.7 inflammatory model was used to investigate the effects of different mass concentrations(50,100,200 μg/mL)of lipid metabolites on the release of NO and TNF-α after treated for 24 h. RESULTS:A total of 13 compounds were identified in lipid metabolites of A. terreus,among which palmitic acid,stearic acid,linoleic acid and oleic acid were main components,and relative percentages of them were 29.35％,10.87％,21.94％,34.85％. The lipid metabolites displayed anti-bacterial activity against E. coli and K. pneumonia with MICs of 12.5 mg/mL and 50 mg/mL,MBC of 25 mg/mL and 100 mg/mL,respectively. The main 4 compositions could inhibit the growth of E. coli,with MIC of 0.5-1 mg/mL,among which palmitic acid showed significant antibacterial activity,especially to E. faecium(MIC of 0.25 mg/mL). 50,100 μg/mL lipid metabolites could signifiantly inhibit the release of inflammatory factor of NO and TNF-α in RAW264.7 in vitro. CONCLUSIONS:The lipid metabolites of endophytic fungus A. terreus from P. capitatum show anti- multi-drug resistant bacteria and anti-inflammatory effects.

Aspergilosis invasora post-quirúrgica: presentación de caso clínico / Invasive aspergillosis post surgical: presentation of case

La aspergilosis invasora es una infección oportunista causada por hongos del género Aspergillus spp, considerándose la con peor pronóstico producida por este organismo. Presenta una elevada tasa de mortalidad a pesar del avance en los tratamientos antifúngicos, afectando principalmente a pacientes inmunosuprimidos. Dentro de las formas clínicas se encuentra la que sucede posterior a una cirugía conllevando una elevada morbi-mortalidad. Presentamos un caso clínico del Hospital Roberto Del Río. Recién nacido de término diagnosticado de transposición de grandes vasos, quien a los 9 días de vida es sometido a cirugía correctora. Egresa de pabellón con tórax abierto y con requerimiento de drogas vasoactivas. Al décimo día postoperatorio presenta deterioro hemodinámico, se realiza ecocardiograma que muestra líquido con ecorefringencias y se realiza aseo quirúrgico, extrayendo muestra para cultivo que resulta positivo para Aspergillus terreus. Por consiguiente, se inicia tratamiento con voriconazol con buena respuesta clínica...

Invasive aspergillosis is an opportunistic infection caused by fungi of the genus Aspergillus spp, considered the worst prognosis produced by this organism. It has a high mortality despite progress in antifungal treatments, affecting mainly immunocompromised patients. Clinically can occur following surgery , leading to high morbidity and mortality. We report a case of Roberto Del Río Hospital. Term newborn diagnosed with transposition of the great vessels, who at 9 days of life undergoes corrective surgery. Leaves the pavilion with open chest and requirement of vasoactive drugs. On the tenth day after surgery presents hemodynamic deterioration, the echocardiogram shows refringence and surgical cleaning is performed, a sample is removed and cultured resulting positive for Aspergillus terreus. Therefore, treatment with voriconazole starts with good clinical response...

Characterization of biotechnologically relevant extracellular lipase produced by Aspergillus terreus NCFT 4269.10

Abstract Enzyme production by Aspergillus terreus NCFT 4269.10 was studied under liquid static surface and solid-state fermentation using mustard oil cake as a substrate. The maximum lipase biosynthesis was observed after incubation at 30 °C for 96 h. Among the domestic oils tested, the maximum lipase biosynthesis was achieved using palm oil. The crude lipase was purified 2.56-fold to electrophoretic homogeneity, with a yield of 8.44%, and the protein had a molecular weight of 46.3 kDa as determined by SDS-PAGE. Enzyme characterization confirmed that the purified lipase was most active at pH 6.0, temperature of 50 °C, and substrate concentration of 1.5%. The enzyme was thermostable at 60 °C for 1 h, and the optimum enzyme–substrate reaction time was 30 min. Sodium dodecyl sulfate and commercial detergents did not significantly affect lipase activity during 30-min incubation at 30 °C. Among the metal ions tested, the maximum lipase activity was attained in the presence of Zn2+, followed by Mg2+ and Fe2+. Lipase activity was not significantly affected in the presence of ethylenediaminetetraacetic acid, sodium lauryl sulfate and Triton X-100. Phenylmethylsulfonyl fluoride (1 mM) and the reducing, β-mercaptoethanol significantly inhibited lipase activity. The remarkable stability in the presence of detergents, additives, inhibitors and metal ions makes this lipase unique and a potential candidate for significant biotechnological exploitation.

A Case of Toenail Onychomycosis Due to Aspergillus terreus / 대한의진균학회지

Onychomycosis is caused by dermatophytes usually, but some species of nondermatophytic molds and yeasts are also associated with invasion of nails. Aspergillus(A.) terreus is a nondermatophytic mold which is opportunistic filamentous fungus in all environments. We report a case of onychomycosis caused by A. terreus in a 60-year-old male. The patient showed brownish yellow discoloration with hyperkeratotic change on the distal and lateral portion of both toenails. Direct microscopic examination of scraping on the potassium hydroxide preparation revealed septate hyphae and repeated cultures on Sabouraud's dextrose agar showed the velvety, cinnamon brown colonies. Biseriate and compactly columnar phialides that cover upper vesicle with conidial structure were shown in the slide culture. The DNA sequence of internal transcribed spacer (ITS) region of clinical sample was 99% match to that of A. terreus strain ATCC 20542 (GenBank accession number GU256759.1). We confirmed A. terreus by KOH mount, colony, light microscopic morphology and DNA sequence analysis. The patient was treated with 200 mg oral itraconazole daily and topical 5% amorolfine nail lacquer for 3 months.

Enhanced alkaline cellulases production by the thermohalophilic Aspergillus terreus AUMC 10138 mutated by physical and chemical mutagens using corn stover as substrate

Abstract A thermohalophilic fungus, Aspergillus terreus AUMC 10138, isolated from the Wadi El-Natrun soda lakes in northern Egypt was exposed successively to gamma and UV-radiation (physical mutagens) and ethyl methan-sulfonate (EMS; chemical mutagen) to enhance alkaline cellulase production under solid state fermentation (SSF) conditions. The effects of different carbon sources, initial moisture, incubation temperature, initial pH, incubation period, inoculum levels and different concentrations of NaCl on production of alkaline filter paper activity (FPase), carboxymethyl cellulase (CMCase) and β-glucosidase by the wild-type and mutant strains of A. terreus were evaluated under SSF. The optimum conditions for maximum production of FPase, CMCase and β-glucosidase were found to be the corn stover: moisture ratio of 1:3(w/v), temperature 45 °C, pH range, 9.0–11.0, and fermentation for 4, 4 and 7 day, respectively. Inoculum levels of 30% for β-glucosidase and 40% for FPase, CMCase gave the higher cellulase production by the wild-type and mutant strains, respectively. Higher production of all three enzymes was obtained at a 5% NaCl. Under the optimized conditions, the mutant strain A. terreus M-17 produced FPase (729 U/g), CMCase (1,783 U/g), and β-glucosidase (342 U/g), which is, 1.85, 1.97 and 2.31-fold higher than the wild-type strain. Our results confirmed that mutant strain M-17 could be a promising alkaline cellulase enzyme producer employing lignocellulosics especially corn stover.

Fumigaclavine I, a new alkaloid isolated from endophyte Aspergillus terreus / 中国天然药物

The present study was designed to isolate and purify chemical constituents from solid culture of endophyte Aspergillus terreus LQ, using silica gel column chromatography, gel filtration with Sephadex LH-20, and HPLC. Fumigaclavine I (1), a new alkaloid, was obtained, along with seven known compounds, including fumigaclavine C (2), rhizoctonic acid (3), monomethylsulochrin (4), chaetominine (5), spirotryprostatin A (6), asperfumoid (7), and lumichrome (8). The structure of compound 1 was elucidated by various spectroscopic analyses (UV, MS, 1D and 2D NMR). The in vitro cytotoxicity of compound 1 was determined by MTT assay in human hepatocarcinoma cell line SMMC-7721, showing weaker cytotoxicity, compared with cisplatin, a clinically used cancer chemotherapeutic agent.

Cellulase Producing Potential of Aspergillus terreus Uv2 on Cellulosic Wastes Pretreated with Acid and Alkali.

Aims: Cellulases offer very wide applications in biotechnology and enzymes from microbial origins present inexpensive source. Production of value added chemicals from wastes will be an exciting translation from waste to wealth and an eco-friendly initiative instead of the incineration option often given to cellulosic wastes. Study Design: Sulphuric acid and Sodium hydroxide solutions were prepared at 0.5 M and 2 M concentrations to pretreat three cellulosic wastes that had been made neutral prior to fermentation with a known cellulase producing mold Place and Duration of Study: All experiments were conducted in the laboratory of the Department of Microbiology, Federal University of Technology, Minna, Nigeria for a period of six weeks. Methodology: Hypercellulase producing Aspergillus terreus UV2 strain was used to ferment pretreated cellulosic wastes: Corn cob, corn straw and bagasse, using submerged fermentation in Mandel basal medium. The crystalline lignocelluloses were milled and fractionated into 850 μ particle size and pretreated in two concentrations (0.5 M and 2 M) of both acid (sulphuric acid) and alkali (sodium hydroxide) independently and were left for varying residence time of one hour or three hours in the digester at ambient temperature, Optimum spore concentration of 1.0 x 106 spores/ml and pH of 4.8. Supernatants of crude enzyme were taken and assayed at 24 hours interval. Results: Cellulase activity peaked at 96 hours. Enzyme secretion in the cellulosic wastes was highest in sugarcane bagasse, followed by the corn cob and then the corn straw corresponding to 51%, 40% and 16% respectively. Alkali pretreated cellulosics gave higher yield of cellulase than its counterpart acid. Non-pretreated residues gave only low enzyme titers. Bagasse produced optimum cellulase yield of 0.068 IU/ml/min within 120 hours when subjected to 2 M NaOH digestion for one hour before fermentation. This translated to 39% increase in enzyme expression when compared with non-treated bagasse of 0.049 IU/ml/min. Conclusion: Sugarcane bagasse therefore when digested with mild alkali (2 M NaOH) for a pretreatment period of one hour holds a great possibility for cellulase production using a mutant mold, Aspergillus terreus UV2. Production of value added chemicals from cellulosic wastes will be an exciting translation from waste to wealth.

Endophytic Fungi: A Poor Candidate for the Production of Lovastatin.

Aim: The aim of the present study was to screen soil and endophytic fungi for production of lovastatin. Methodology: Soil fungi were isolated by dilution plating technique and endophytic fungi from selected medicinal plants by using standard procedures. All isolates were tested for lovastatin production by Solid State Fermentation (SSF) using wheat bran as substrate. Results: The soil isolate, Aspergillus terreus NCBI (KM017963) showed positive for lovastatin (1.0 mg/G DWS) whereas none of the endophytic fungi tested showed positivefor lovastatin production.

Aspergillus terreus endogenous endophthalmitis: Report of a case and review of literature.

We report a rare case of Aspergillus terreus endogenous endophthalmitis in an immunocompetent patient with subretinal abscess and also review the reported cases. A 50-year-old healthy male presented with sudden painful loss of vision in right eye. He was diagnosed with endogenous endophthalmitis and underwent urgent vitrectomy. Aspergillus terreus growth was obtained in culture. At fi nal follow-up, there was complete resolution of the infection but visual acuity was poor due to macular scar. Aspergillus terreus is a rare cause of endophthalmitis with usually poor outcomes. Newer antifungals like Voriconazole can be sometimes associated with better prognosis.

Peptidase with Keratinolytic Activity Secreted by Aspergillus terreus During Solid-State Fermentation

The aim of this study was to evaluate peptidase production by Aspergillus terreus in solid-state bioprocess and evaluate its parameters. The best conditions were 5.0 g of wheat bran as substrate, incubation temperature 30°C, inoculum 2.0x105 spores/g and 75% saline volume, with production reaching 677 U/mL (5400 U/g culture medium) after 72 h of fermentation. Biochemical characterization of the crude enzymatic extract showed the optimum pH and temperature of 6.5 and 55°C, respectively. The stability at different temperatures and pH values showed that the extract could endure different pH. The evaluation of the ions influence and inhibitors proved that the enzyme required an ion for better activity, which was corroborated with the inhibition of EDTA and PMSF, characterizing serine and/or metallo peptidase. The extract was also tested for specific activities and showed promising results for keratinolytic and collagenolytic activities (0.252 and 0.165 OD/mL, respectively).

A case of dual infection in a paediatric trauma victim of primary cutaneous aspergillosis caused by Aspergillus flavus and Aspergillus terreus.

Aspergillus spp. are widely distributed throughout the environment. They are opportunistic pathogens causing infection at various sites in the body such as lungs, sinuses, eyes, skin, central nervous system etc., Primary cutaneous aspergillosis is an uncommon disease entity. Primary infections usually occur at sites having disruption of the skin and usually occur in burn patients, trauma and surgical patients. A 4-year-old girl who was run over by a truck and suffered extensive de-gloving injury to bilateral lower limbs developed greenish discharge and scaly lesions around the wound margins after 50 days of hospital stay. The skin biopsy demonstrated the presence of thin septate hyphae branching at acute angles and culture demonstrated growth of Aspergillus flavus and Aspergillus terreus. The child was started on voriconazole therapy for 3 weeks and the lesion healed satisfactorily. Subsequent skin biopsy culture was negative for fungi. Prompt diagnosis and management of such cases can salvage the limbs in severe trauma cases.

Physiological studies on carboxymethyl cellulase formation by Aspergillus terreus DSM 826

Physiological studies were conducted to determine the optimum cultural conditions for maximal carboxymethyl cellulase (CMCase) formation by Aspergillus terreus DSM 826. Shaking condition at 150 rpm is favorable for the production of CMCase from rice straw and sugar cane bagasse. The highest enzyme yield was obtained at the third day of incubation at 30ºC for both cases; however CMCase formation occurred at a broad range of pH values, with maximal formation of A. terreus DSM 826 CMCase at pH 4.5 and 5.0 when rice straw and sugar cane bagasse were used as sole carbon source, respectively. Carboxymethyl cellulose (CMC) was found to be a good inducer for CMCase formation in both agricultural wastes with CMC concentrations of 0.5 and 1.0 % (w/v) in case of rice straw and sugar cane bagasse, respectively. High level of enzyme formation was obtained with the addition of ammonium chloride as nitrogen source in both cases and at a concentration of 0.4 % (v/v Tween-80) as an addition to medium containing rice straw. However this addition did not influence the production of CMCase in case of using sugar cane bagasse as carbon source.

Successful Treatment of Pneumonia caused by Aspergillus terrerus and Cytomegalovirus after Chemotherapy for Acute Myelogenous Leukemia / 감염과화학요법

We report a case of pneumonia caused by Aspergillus terreus and cytomegalovirus (CMV) in a patient with acute myleogenous leukemia (AML) after remission induction chemotherapy. A 19-year-old woman underwent chemotherapy for AML. Twenty-three days after completing chemotherapy, she experienced a neutropenic fever with a rapidly-progressive pulmonary infiltration. In those days, her serum galactomannan immunoassay was 4.7 and she was treated with intravenous voriconazole (6 mg/kg q12h for 2 doses, followed by 4 mg/kg q12h) because of persistent fever and radiological worsening, despite the administration of amphotericin B deoxycholate (1 mg/kg q24h) for 7 days. A chest CT showed wedge-shaped consolidation with a central hypodense lesion and an air-crescent sign in the right middle lobe. With maintenance therapy of oral voriconazole for 10 weeks, a partial response was shown and neutrophil count was still less than 100/mm3. A lobectomy of the right middle lobe was performed. A. terreus was discovered from the lung tissue. At the same time, giant cells with intranuclear inclusions were found and immunohistochemical staining for CMV was positive. Ganciclovir (5 mg/kg q12h) was added to voriconazole therapy for 3 weeks after surgery, and then cord blood hematopoietic stem cell transplantation (HSCT) was performed. During HSCT, foscarnet (60 mg/kg q12h) was substituted for ganciclovir, and both antiviral agents were used alternatively due to CMV DNAemia. After 83 days from HSCT, the patient achieved successful engraftment and discharged without worsening the pneumonia.

Modification of c and n sources for enhanced production of cyclosporin 'a' by Aspergillus Terreus

Most of the studies regarding cyclosporin 'A' production through fungi concentrate around Tolypocladium inflatum. This is mainly due to lower reported production of this drug in other fungi. The present study was therefore conducted to explore indigenous isolates of Aspergillus terreus for synthesis of this drug and defining a production medium for obtaining high yield of cyclosporin 'A'. For this purpose carbon and nitrogen sources were optimized for the selected best strain of A. terreus. Overall results depicted that the best cyclosporin 'A' yield from selected Aspergillus terreus (FCBP58) could be obtained by using production medium containing glucose 10 percent as carbon source and peptone 0.5 percent as nitrogen source. This modification in production medium enhanced drug synthesis by selected fungi significantly. The production capabilities when compared with biomass of fungi there was found no relationship between the two confirming that the medium modification increased overall drug synthesis powers of the fungi.