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aspergillus fumigatus keratitis following intracorneal ring segment implantation.fungal keratitis has been rarely reported following intracorneal ring segment (icrs) inmplantation. this paper aims to report a case of fungal keratitis with aspergillus fumigatus following icrs implantation for correction of keratoconus.201222769849
correlation between triazole treatment history and susceptibility in clinically isolated aspergillus fumigatus.this is the first report of a detailed relationship between triazole treatment history and triazole mics for 154 aspergillus fumigatus clinical isolates. the duration of itraconazole dosage increased as the itraconazole mic increased, and a positive correlation was observed (r = 0.5700, p < 0.0001). the number of itraconazole-naïve isolates dramatically decreased as the itraconazole mic increased, particularly for mics exceeding 2 μg/ml (0.5 μg/ml versus 2 μg/ml, p = 0.03). we also examined the ...201222751542
protein phosphatase z modulates oxidative stress response in fungi.the genome of the filamentous fungus aspergillus nidulans harbors the gene ppza that codes for the catalytic subunit of protein phosphatase z (ppz), and the closely related opportunistic pathogen aspergillus fumigatus encompasses a highly similar ppz gene (phza). when ppza and phza were expressed in saccharomyces cerevisiae or schizosaccharomyces pombe they partially complemented the deleted phosphatases in the ppz1 or the pzh1 mutants, and they also mimicked the effect of ppz1 overexpression in ...201222750657
[azole resistance in aspergillus fumigatus in the netherlands--increase due to environmental fungicides?].the mould aspergillus fumigatus may develop mechanisms that confer resistance to itraconazole, voriconazole and posaconazole. in the netherlands a dominant resistance mechanism referred to as tr/l98h is found. in a. fumigatus isolates recovered from clinical samples in dutch hospitals the prevalence of azole resistance varied between 0.8% and 9.4%. the tr/l98h resistance mechanism probably develops in our environment, as azoles are frequently used for crop protection and material preservation. i ...201222748367
frequency of fungi in respiratory samples from turkish cystic fibrosis patients.an increased isolation of fungi from the respiratory tract of patients with cystic fibrosis (cf) has been reported. the prevalence of different fungi in cf patients from turkey is not known. our aim was to determine the frequency of fungi in the respiratory tract of turkish cf patients. we investigated a total of 184 samples from 48 patients. samples were inoculated on medium b+ and chromagar candida. candida albicans was the predominant yeast isolated [30 patients (62.5%)], followed by c. parap ...201322747891
selection of thermophilic and thermotolerant fungi for the production of cellulases and xylanases under solid-state fermentation.twenty-seven thermophilic and thermotolerant fungal strains were isolated from soil, decaying organic matter and sugarcane piles based on their ability to grow at 45°c on medium containing corn straw and cardboard as carbon sources. these fungi were identified in the genera aspergillus, thermomyces, myceliophthora, thermomucor and candida. the majority of the isolated strains produced xylanase and cellulases under solid state fermentation (ssf). the highest cellulase and xylanase productions wer ...201224031929
obstruction of a percutaneous pulmonary valve by an aspergillus mycotic thrombus mimicking massive pulmonary embolus.new technologies in the management of congenital and acquired heart disease may be associated with unfamiliar complications that may require repeated surgical intervention. a high index of suspicion for unusual problems and close collaboration between cardiologists and surgeons is essential when adopting evolving technologies. we report the case of near total obstruction of a 2.5-month-old implanted melody percutaneous pulmonary valve (ppv) with a thrombus mimicking saddle embolus causing right ...201222735023
μ-chain-deficient mice possess b-1 cells and produce igg and ige, but not iga, following systemic sensitization and inhalational challenge in a fungal asthma model.allergic bronchopulmonary aspergillosis is often difficult to treat and results in morbidity associated with chronic airway changes. this study assessed the requirement for b cells and their products in the allergic pulmonary phenotype in a murine model of fungal allergic asthma that mimics allergic bronchopulmonary aspergillosis. c57bl/6 and μmt mice (assumed to lack peripheral b cells) were sensitized with aspergillus fumigatus extract and challenged with two inhalation exposures of live conid ...201222732592
[role of neutrophil-derived reactive oxygen species in host defense and inflammation].neutrophil accumulation is a critical event in the pathogenesis of inflammation. the generation of hypochlorous acid by myeloperoxidase (mpo) in neutrophils is crucial to the host defense response. mpo-deficient (mpo-ko) mice showed severely reduced cytotoxicity to candida albicans, aspergillus fumigatus, cryptococcus neoformans and other microorganisms, demonstrating that an mpo-dependent oxidative system is important for in vivo host defense against fungi. on the other hand, impaired reactive ...201222728595
characteristics of nucleosomes and linker dna regions on the genome of the basidiomycete mixia osmundae revealed by mono- and dinucleosome mapping.we present findings on the nucleosomal arrangement in the genome of the basidiomycete mixia osmundae, focusing on nucleosomal linker dna regions. we have assembled the genomic sequences of m. osmundae, annotated genes and transcription start sites (tsss) on the genome, and created a detailed nucleosome map based on sequencing mono- and dinucleosomal dna fragments. the nucleosomal dna length distribution of m. osmundae is similar to that of the filamentous ascomycete aspergillus fumigatus, but di ...201222724063
non occupational chronic hypersensitivity pneumonitis due to aspergillus fumigatus on leaky walls. 201222722814
the transcriptional response to the inactivation of the pampk1 and pampk2 map kinase pathways in podospora anserina.transcription pattern during mycelium growth of podospora anserina was assayed by microarray analysis in wild type and in mutants affected in the map kinase genes pampk1 and pampk2 and in the nadph oxidase gene panox1. 15% of the genes have their expression modified by a factor two or more as growth proceeds in wild type. the genes whose expression is modified during growth in p. anserina are either not conserved or differently regulated in neurospora crassa and aspergillus niger, two fungi for ...201222721649
azole preexposure affects the aspergillus fumigatus population in patients.the relationship between the azole preexposure of 86 patients and the genotype, azole susceptibility, and cyp51a polymorphisms of 110 corresponding aspergillus fumigatus isolates was explored. isolates carrying serial polymorphisms (f46y and m172v with or without n248t with or without d255e with or without e427k) had higher itraconazole mics (p = 0.04), although <2 μg/ml using the eucast methodology, were associated with two genetic clusters (p < 0.001) and with voriconazole preexposure of patie ...201222710122
immunity and tolerance to fungi in hematopoietic transplantation: principles and perspectives.resistance and tolerance are two complementary host defense mechanisms that increase fitness in response to low-virulence fungi. resistance is meant to reduce pathogen burden during infection through innate and adaptive immune mechanisms, whereas tolerance mitigates the substantial cost of resistance to host fitness through a multitude of anti-inflammatory mechanisms, including immunological tolerance. in experimental fungal infections, both defense mechanisms are activated through the delicate ...201222707953
antifungal therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.allergic bronchopulmonary aspergillosis (abpa) is an allergic reaction to colonisation of the lungs with the fungus aspergillus fumigatus and affects around 10% of people with cystic fibrosis. abpa is associated with an accelerated decline in lung function. high doses of corticosteroids are the main treatment for abpa; although the long-term benefits are not clear, their many side effects are well-documented. a group of compounds, the azoles, have activity against aspergillus fumigatus and have ...201222696329
adoptive immunity mediated by hla-a*0201 restricted asp f16 peptides-specific cd8+ t cells against aspergillus fumigatus infection.aspergillus fumigatus (a. fumigatus) is the most common pathogen of invasive aspergillosis (ia), a life-threatening infection in immunocompromised patients. recent findings revealed that cd8+ t cells can mediate cytotoxic activity against a. fumigatus. here, we bioinformatically identified three hla-a*0201-restricted peptides from asp f16, an a. fumigatus antigen which was previously shown to be involved in t cell immunity. our immunological results demonstrated that these peptides can potently ...201222696051
amino acid-derived 1,2-benzisothiazolinone derivatives as novel small-molecule antifungal inhibitors: identification of potential genetic targets.we have identified four synthetic compounds (dfd-vi-15, bd-i-186, dfd-v-49, and dfd-v-66) from an amino acid-derived 1,2-benzisothiazolinone (bzt) scaffold that have reasonable mic(50) values against a panel of fungal pathogens. these compounds have no structural similarity to existing antifungal drugs. three of the four compounds have fungicidal activity against candida spp., cryptococcus neoformans, and several dermatophytes, while one is fungicidal to aspergillus fumigatus. the kill rates of ...201222687516
experimental central nervous system aspergillosis therapy: efficacy, drug levels and localization, immunohistopathology, and toxicity.we have shown previously that high-dose lipid amphotericin preparations are not more efficacious than lower doses in aspergillosis. we studied toxicity, drug concentrations and localization, and quantitative infection concurrently, using a 4-day model of central nervous system (cns) aspergillosis to assess early events. mice given aspergillus fumigatus conidia intracerebrally, under a cyclophosphamide immunosuppressive regimen, were treated for 3 days (ambisome at 3 or 10 mg/kg of body weight, a ...201222687510
purification, crystallization and preliminary x-ray diffraction data of udp-galactopyranose mutase from aspergillus fumigatus.aspergillus fumigatus udp-galactopyranose mutase (afugm) is a potential drug target involved in the synthesis of the cell wall of this fungal pathogen. afugm was recombinantly produced in escherichia coli, purified and crystallized by the sitting-drop method, producing orthorhombic crystals that diffracted to a resolution of 3.25 å. the crystals contained four molecules per asymmetric unit and belonged to space group p2(1)2(1)2(1), with unit-cell parameters a = 127.72, b = 134.30, c = 173.84 å. ...201222684076
hog-mapk signaling regulates the adaptive responses of aspergillus fumigatus to thermal stress and other related stress.aspergillus fumigatus is naturally exposed to a highly variable environment and subjected to various kinds of stresses. high-osmolarity glycerol mitogen-activated protein kinase (hog-mapk) pathway plays a crucial role in regulating cellular homeostasis in response to environmental changes. here, we explored the contribution of hog-mapk pathway to the adaptive responses to thermal stress and other related stresses in a. fumigatus. we observed the phenotype features of wild-type strains and their ...201222678624
the two-component sensor kinase tcsc and its role in stress resistance of the human-pathogenic mold aspergillus fumigatus.two-component signaling systems are widespread in bacteria, but also found in fungi. in this study, we have characterized tcsc, the only group iii two-component sensor kinase of aspergillus fumigatus. tcsc is required for growth under hyperosmotic stress, but dispensable for normal growth, sporulation and conidial viability. a characteristic feature of the δtcsc mutant is its resistance to certain fungicides, like fludioxonil. both hyperosmotic stress and treatment with fludioxonil result in a t ...201222675534
molecular epidemiology of aspergillus fumigatus isolates harboring the tr34/l98h azole resistance mechanism.a rapid emergence of azole resistance has been observed in aspergillus fumigatus in the netherlands over the past decade. the dominant resistance mechanism appears to be of environmental origin and involves the tr(34)/l98h mutations in cyp51a. this resistance mechanism is now also increasingly being found in other countries. therefore, genetic markers were used to gain more insights into the origin and spread of this genotype. studies of 142 european isolates revealed that those with the tr(34)/ ...201222675126
restriction analysis of an amplified roda gene fragment to distinguish aspergillus fumigatus var. ellipticus from aspergillus fumigatus var. fumigatus.a previous multidisciplinary study indicated that gliotoxin-producing aspergillus fumigatus fresen. isolates from silage commodities mostly belonged to its variant a. fumigatus var. ellipticus raper & fennell. sequence analysis revealed the presence of a single nucleotide polymorphism at five positions in a fragment of the roda gene (coding for a hydrophobin rodleta protein) between aspergillus fumigatus var. fumigatus and aspergillus fumigatus var. ellipticus. a method was developed to distingu ...201222670589
development of monoclonal antibody-based galactomannoprotein antigen-capture elisas to detect aspergillus fumigatus infection in the invasive aspergillosis rabbit models.aspergillus fumigatus is one of the most prominent opportunistic fungal pathogens in immunocompromised hosts. early recognition of this infection along with prompt antifungal therapy may increase the survival rate. we expressed two potential bio-markers of a. fumigatus infection-galactomannoprotein afmp1p and afmp4p in pichia pastoris. we generated 33 monoclonal antibodies (mabs), 20 against recombinant afmp1p (rafmp1p) and the other 13 against recombinant afmp4p (rafmp4p). subsequently, we deve ...201222669560
a new type of hypersensitivity pneumonitis: salami brusher's disease.we observed five consecutive cases of hypersensitivity pneumonitis in subjects working in a salami factory. the workers had to clean the white mould growing on salami surface using a manual wire brush. the five patients (four female) had a mean age of 39 +/- 15 years; two were smokers. three patients had an acute clinical presentation with fever, dyspnoea, dry cough, oxygen desaturation, and presented at the emergency department with suspected diagnosis of community acquired pneumonia. the mean ...201222662646
functional characterization of an aspergillus fumigatus calcium transporter (pmca) that is essential for fungal infection.aspergillus fumigatus is a primary and opportunistic pathogen, as well as a major allergen, of mammals. the ca(+2)-calcineurin pathway affects virulence, morphogenesis and antifungal drug action in a. fumigatus. here, we investigated three components of the a. fumigatus ca(+2)-calcineurin pathway, pmca,-b, and -c, which encode calcium transporters. we demonstrated that crza can directly control the mrna accumulation of the pmca-c genes by binding to their promoter regions. crza-binding experimen ...201222649543
crystal structures of trypanosoma cruzi udp-galactopyranose mutase implicate flexibility of the histidine loop in enzyme activation.chagas disease is a neglected tropical disease caused by the protozoan parasite trypanosoma cruzi. here we report crystal structures of the galactofuranose biosynthetic enzyme udp-galactopyranose mutase (ugm) from t. cruzi, which are the first structures of this enzyme from a protozoan parasite. ugm is an attractive target for drug design because galactofuranose is absent in humans but is an essential component of key glycoproteins and glycolipids in trypanosomatids. analysis of the enzyme-udp n ...201222646091
aspergillus endocarditis in a native valve without prior cardiac surgery.aspergillus native valve endocarditis continues to be a lethal disease, even when maximal therapeutic options are taken. we describe herein a patient with mitral valve endocarditis due to aspergillus fumigatus following colon cancer and invasive pulmonary aspergillosis. voriconazole was effective in controlling pulmonary and cerebral aspergillosis, despite the relative ineffectiveness for the vegetation. with the combination of aggressive medical and surgical therapy, the patient survived and re ...201222644820
prenylation of a nonaromatic carbon of indolylbutenone by a fungal indole prenyltransferase.ftmpt1 from aspergillus fumigatus is a fungal indole prenyltransferase (pt) that normally catalyzes the regiospecific prenylation of brevianamide f (cyclo-l-trp-l-pro) at the c-2 position of the indole ring with dimethylallyl diphosphate (dmapp). interestingly, ftmpt1 exhibited remarkable substrate tolerance and accepted (e)-4-(1h-indol-3-yl)but-3-en-2-one (1) as a substrate to produce an unnatural novel α-prenylindolylbutenone (1a). this is the first demonstration of the prenylation of a nonaro ...201222642693
plga nanoparticles and nanosuspensions with amphotericin b: potent in vitro and in vivo alternatives to fungizone and ambisome.this paper describes the development of poly(d,l-lactide-co-glycolide) (plga) nanoparticles (nps) and nanosuspensions with the polyene antibiotic amphotericin b (amb). the nanoformulations were prepared using nanoprecipitation and were characterised with respect to size, zeta potential, morphology, drug crystallinity and content. standard in vitro sensitivity tests were performed on mrc-5 cells, red blood cells, leishmania infantum promastigotes and intracellular amastigotes and the fungal speci ...201222641062
allergic bronchopulmonary aspergillosis.allergic bronchopulmonary aspergillosis (abpa) is caused by an exaggerated t(h)2 response to the ubiquitous mold aspergillus fumigatus. abpa develops in a small fraction of patients with cystic fibrosis and asthma, suggesting that intrinsic host defects play a major role in disease susceptibility. this article reviews current understanding of the immunopathology, clinical and laboratory findings, and diagnosis and management of abpa. it highlights clinical and laboratory clues to differentiate a ...201222640845
pharmacodynamics of voriconazole in a dynamic in vitro model of invasive pulmonary aspergillosis: implications for in vitro susceptibility breakpoints.voriconazole is a first-line agent for the treatment of invasive pulmonary aspergillosis (ipa). there are increasing reports of aspergillus fumigatus isolates with reduced susceptibility to voriconazole.201222634880
aspergillus fumigatus calcineurin interacts with a nucleoside diphosphate kinase.the ca(2+)-calcineurin pathway affects virulence and morphogenesis in filamentous fungi. here, we identified 37 cala-interacting proteins that interact with the catalytic subunit of calcineurin (cala) in aspergillus fumigatus, including the nucleoside diphosphate kinase (swoh). the in vivo interaction between cala and swoh was validated by bimolecular fluorescence complementation. a. fumigatus swoh is an essential gene. therefore, a temperature-sensitive conditional mutant strain with a point mu ...201222634424
salvage therapy with topical antifungal for aspergillus fumigatus empyema complicating extrapleural pneumonectomy.we describe an unusual case of aspergillus fumigatus empyema and bronchopleural fistulae after extrapleural pneumonectomy (epp) and chemoradiotherapy (crt), which was treated successfully under salvage conditions with debridement, an innovative topical antifungal application and supplemented systemic antifungal therapy and which went on for a definitive surgical procedure. combinations of crt and epp have been recommended in a select group of patients with malignant mesothelioma. irrespective of ...201222617507
pharmacodynamics of itraconazole against aspergillus fumigatus in an in vitro model of the human alveolus: perspectives on the treatment of triazole-resistant infection and utility of airway administration.itraconazole is used for the prevention and treatment of infections caused by aspergillus fumigatus. an understanding of the pharmacodynamics of itraconazole against wild-type and triazole-resistant strains provides a basis for innovative therapeutic strategies for treatment of infections. an in vitro model of the human alveolus was used to define the pharmacodynamics of itraconazole. galactomannan was used as a biomarker. the effect of systemic and airway administration of itraconazole was asse ...201222615280
pseudomembranous necrotizing tracheobronchial aspergillosis: an analysis of 16 cases.in our clinical practice we have been attracted by a group of patients with airway aspergillosis who have airway obstruction; we termed the condition as pseudomembranous necrotizing tracheobronchial aspergillosis (pnta). in this study we analyzed the clinical data from patients with pnta, so as to guide the diagnosis and treatment of the disease.201222613594
orbital aspergillosis: voriconazole - the new standard treatment?to describe a case of invasive orbital aspergillosis and evaluate treatments and outcomes.201222611368
incidence of dsrna mycoviruses in a collection of aspergillus fumigatus isolates.a collection of clinical and environmental isolates of the opportunistic human pathogen, aspergillus fumigatus, were screened for the presence of mycoviruses and 6.6 % of 366 isolates contained dsrna segments ranging in size from ~1.0 to 4.0 kbp. the dsrnas were categorised into three different groups comprising bipartite dsrnas, quadripartite dsrnas, representative isolates of which have both been sequenced, and an uncharacterised mycovirus, whose genome apparently consists of four dsrnas 1-2.5 ...201222610906
blood basophils from cystic fibrosis patients with allergic bronchopulmonary aspergillosis are primed and hyper-responsive to stimulation by aspergillus allergens.fifteen to sixty percent of cystic fibrosis patients harbor aspergillus fumigatus (af) in their airways (cf-ac) and some will develop allergic bronchopulmonary aspergillosis (cf-abpa). since basophils play a key role in allergy, we hypothesized that they would display alterations in cf-abpa patients compared to cf-ac or patients without af colonization (cf).201222608296
in vitro efficacy of the combination of voriconazole and anidulafungin against voriconazole-resistant cyp51a mutants of aspergillus fumigatus.we selected voriconazole-resistant (vcz-r) aspergillus fumigatus in the laboratory, characterized the cyp51a gene for possible mutations and evaluated the in vitro activities of voriconazole and anidulafungin alone and in combination against vcz-r isolates of a. fumigatus using a fractional inhibitory concentration index (fici) methodology. voriconazole-resistant isolates were selected from wild-type a. fumigatus isolates in the laboratory by a 2-step selection process (plus 1 clinical isolate). ...201222608136
antifungal cyclic peptides from the marine sponge microscleroderma herdmani.screening natural product extracts from the national cancer institute open repository for antifungal discovery afforded hits for bioassay-guided fractionation. using lc-ms analysis to generate chemical structure information on potentially active compounds, two new cyclic hexapeptides, microsclerodermins j (1) and k (2), were isolated from the deep-water sponge microscleroderma herdmani, along with microsclerodermins a (3) and b (4), previously isolated from an unidentified microscleroderma speci ...201223936761
prenatal exposure to allergen, dna methylation, and allergy in grandoffspring mice.prenatal allergen exposure has been linked to both induction and protection of allergic sensitization in offspring. we hypothesized that prenatal exposure of mice (f0) to aspergillus fumigatus (a. fumigatus) would be associated with decreased immunoglobulin (ig) e and airway eosinophilia and alterations in cpg methylation of t-helper genes in third-generation mice (f2).201222583153
high prevalence of triazole resistance in aspergillus fumigatus, especially mediated by tr/l98h, in a french cohort of patients with cystic fibrosis.triazole resistance in aspergillus fumigatus due to a single azole resistance mechanism (tr/l98h) is increasingly reported in european countries. data from patients with cystic fibrosis (cf) are limited. our study aimed to investigate the prevalence and molecular mechanisms of azole resistance in a. fumigatus in a cohort of patients with cf.201222581906
new metabolites from the marine-derived fungus aspergillus fumigatus.a new alkaloid, fumiquinazoline k (1), and a new nordammarane triterpenoid (2), together with three known diketopiperazines (3-5) and tryptoquivaline f (6) have been isolated from a marine strain of aspergillus fumigatus kmm 4 631 associated with the soft coral sinularia sp. their structures were determined by hr-ms and 1d and 2d nmr. compounds 3-5 exhibit weak cytotoxicity against cytoplasm non-specific esterase in ehrlich carcinoma cells. compound 3 also induces early apoptosis of the same cel ...201222574452
identification and characterization of antifungal compounds using a saccharomyces cerevisiae reporter bioassay.new antifungal drugs are urgently needed due to the currently limited selection, the emergence of drug resistance, and the toxicity of several commonly used drugs. to identify drug leads, we screened small molecules using a saccharomyces cerevisiae reporter bioassay in which s. cerevisiae heterologously expresses hik1, a group iii hybrid histidine kinase (hhk) from magnaporthe grisea. group iii hhks are integral in fungal cell physiology, and highly conserved throughout this kingdom; they are ab ...201222574132
resistance to voriconazole due to a g448s substitution in aspergillus fumigatus in a patient with cerebral aspergillosis.a voriconazole-resistant isolate of aspergillus fumigatus was recovered from an immunocompetent patient receiving long-term antifungal therapy for cerebral aspergillosis. a g448s amino acid substitution in the azole target (cyp51a) was identified as the cause of the resistance phenotype. this article describes the first isolation of a voriconazole-resistant a. fumigatus isolate from an immunocompetent patient in spain.201222573589
occlusive fungal tracheitis in 4 captive bottlenose dolphins (tursiops truncatus).respiratory disease is common in dolphins, primarily affecting pulmonary parenchyma and sparing large airways. over a 10-year period, 4 captive adult bottlenose dolphins succumbed to chronic, progressive respiratory disease with atypical recurrent upper respiratory signs. all dolphins had severe, segmental to circumferential fibrosing tracheitis that decreased luminal diameter. histologically, tracheal cartilage, submucosa, and mucosa were distorted and replaced by extensive fibrosis and pyogran ...201322573576
mucoadhesive nanoparticles for prolonged ocular delivery of natamycin: in vitro and pharmacokinetics studies.the aim of this study was to prepare natamycin encapsulated lecithin/chitosan mucoadhesive nanoparticles (nps) for prolonged ocular application. these nps were characterized by their mean particle size 213nm, encapsulation efficiency 73.57%, with a theoretical drug loading 5.09% and zeta potential +43. in vitro release exhibited a biphasic drug release profile with initial burst followed by a very slow drug release. the mic(90) and zone of inhibition of nps showed similar antifungal activity as ...201222569234
treatment of aspergillus fumigatus in patients with cystic fibrosis: a randomized, placebo-controlled pilot study.many patients with cystic fibrosis develop persistent airway infection/colonization with aspergillus fumigatus, however the impact of a. fumigatus on clinical outcomes remains unclear. the objective of this study was to determine whether treatment directed against aspergillus fumigatus improves pulmonary function and clinical outcomes in patients with cystic fibrosis (cf).201222563440
plasma membrane localization is required for rasa-mediated polarized morphogenesis and virulence of aspergillus fumigatus.ras is a highly conserved gtpase protein that is essential for proper polarized morphogenesis of filamentous fungi. localization of ras proteins to the plasma membrane and endomembranes through posttranslational addition of farnesyl and palmitoyl residues is an important mechanism through which cells provide specificity to ras signal output. although the aspergillus fumigatus rasa protein is known to be a major regulator of growth and development, the membrane distribution of rasa during polariz ...201222562470
an efficient one-pot synthesis, structure, antimicrobial and antioxidant investigations of some novel quinolyldibenzo[b,e][1,4]diazepinones.a highly improved one-pot procedure for the synthesis of diazepinones, which incorporate a bioactive quinoline nucleus, under catalyst-, and solvent-free environment has been developed. the method allowed us to achieve the products in high yields without requiring a chromatographic separation. all new quinolyldibenzo[b,e][1,4]diazepinones 6a-h thus obtained were further treated to achieve n10-allylated products 7a-h by a simple allylation. the structure of all new synthesized compounds was estab ...201222560587
agent-based modeling approach of immune defense against spores of opportunistic human pathogenic fungi.opportunistic human pathogenic fungi like the ubiquitous fungus aspergillus fumigatus are a major threat to immunocompromised patients. an impaired immune system renders the body vulnerable to invasive mycoses that often lead to the death of the patient. while the number of immunocompromised patients is rising with medical progress, the process, and dynamics of defense against invaded and ready to germinate fungal conidia are still insufficiently understood. besides macrophages, neutrophil granu ...201222557995
the roles of surfactant protein d during aspergillus fumigatus infection in human corneal epithelial cells.to investigate roles of surfactant protein d (sp-d) and relative cytokines in human corneal epithelial(hce) cells exposed to aspergillus fumigatus (af) antigens.201222553747
organic dust toxic syndrome at a grass seed plant caused by exposure to high concentrations of bioaerosols.we describe an outbreak of sudden health problems in workers at a danish grass seed plant after exposure to a particularly dusty lot of grass seeds. the seeds are called problematic seeds. the association between development of organic dust toxic syndrome (odts) and the handling of grass seeds causing exposure was assessed in a four-step model: (i) identification of exposure source, (ii) characterization of the emission of bioaerosols from the problematic and reference seeds, (iii) personal and ...201222553153
development stage-specific proteomic profiling uncovers small, lineage specific proteins most abundant in the aspergillus fumigatus conidial proteome.the pathogenic mold aspergillus fumigatus is the most frequent infectious cause of death in severely immunocompromised individuals such as leukemia and bone marrow transplant patients. germination of inhaled conidia (asexual spores) in the host is critical for the initiation of infection, but little is known about the underlying mechanisms of this process.201222545825
evaluation of plasma (1-->3) beta-d-glucan concentrations in birds naturally and experimentally infected with aspergillus fumigatus.avian aspergillosis, most often caused by aspergillus fumigatus, is a common and devastating disease affecting a range of bird species. early diagnosis is difficult and often unreliable. the current study evaluated the utility of measuring (1-->3)-beta-d-glucan (bg) concentrations in avian plasma samples to aid in the diagnosis of aspergillosis. we evaluated a commercially available bg assay (fungitell, beacon diagnostics) using 178 plasma samples from naturally infected, experimentally infected ...201222545545
the ram network in pathogenic fungi.the regulation of ace2 and morphogenesis (ram) network is a protein kinase signaling pathway conserved among eukaryotes from yeasts to humans. among fungi, the ram network has been most extensively studied in the model yeast saccharomyces cerevisiae and has been shown to regulate a range of cellular processes, including daughter cell-specific gene expression, cell cycle regulation, cell separation, mating, polarized growth, maintenance of cell wall integrity, and stress signaling. increasing num ...201222544903
the fatty acid 8,11-diol synthase of aspergillus fumigatus is inhibited by imidazole derivatives and unrelated to ppob.(8r)-hydroperoxy-(9z,12z)-octadecadienoic acid (8-hpode) is formed by aspergilli as an intermediate in biosynthesis of oxylipins with effects on sporulation. 8-hpode is transformed by separate diol synthases to (5s,8r)-dihydroxy- and (8r,11s)-dihydroxy-(9z,12z)-octadecadienoic acids (5,8- and 8,11-dihode). the former is formed by the cytochrome p450 (p450) domain of 5,8-linoleate diol synthase (5,8-lds or ppoa). our aim was to characterize the 8,11-diol synthase of aspergillus fumigatus, which i ...201222544380
antifungal activity of lactobacillus against microsporum canis, microsporum gypseum and epidermophyton floccosum.a total of 220 lactic acid bacteria isolates were screened for antifungal activity using aspergillus fumigatus and aspergillus niger as the target strains. four lactobacillus strains exhibited strong inhibitory activity on agar surfaces. all four were also identified as having strong inhibitory activity against the human pathogenic fungi microsporum canis, microsporum gypseum and epidermophyton floccosum. one of the four lactobacilli, namely lb. reuteri ee1p exhibited the most inhibition against ...201722539027
characterisation of innate fungal recognition in the lung.the innate recognition of fungi by leukocytes is mediated by pattern recognition receptors (prr), such as dectin-1, and is thought to occur at the cell surface triggering intracellular signalling cascades which lead to the induction of protective host responses. in the lung, this recognition is aided by surfactant which also serves to maintain the balance between inflammation and pulmonary function, although the underlying mechanisms are unknown. here we have explored pulmonary innate recognitio ...201222536422
microcolony imaging of aspergillus fumigatus treated with echinocandins reveals both fungistatic and fungicidal activities.the echinocandins are lipopeptides that can be employed as antifungal drugs that inhibit the synthesis of 1,3-β-glucans within the fungal cell wall. anidulafungin and caspofungin are echinocandins used in the treatment of candida infections and have activity against other fungi including aspergillus fumigatus. the echinocandins are generally considered fungistatic against aspergillus species.201222536390
analyzing disease risks associated with translocations.translocations of species are expected to be used increasingly to counter the undesirable effects of anthropogenic changes to ecosystems, including loss of species. methods to assess the risk of disease associated with translocations have been compiled in a comprehensive manual of disease-risk analysis for movement of domestic animals. we used this manual to devise a qualitative method for assessing the probability of the occurrence of disease in wild animals associated with translocations. we a ...201222533691
proteomic characterization of aspergillus fumigatus treated with an antifungal coumarin for identification of novel target molecules of key pathways.a synthetic coumarin, n,n,n-triethyl-11-(4-methyl-2-oxo-2h-chromen-7-yloxy)-11-oxoundecan-1-aminium bromide (scd-1), having potent activity against pathogenic aspergilli (mic90 15.62 μg/ml), was investigated to identify its molecular targets in the pathogen. the proteome of aspergillus fumigatus was developed after treatment with sublethal doses of compound and analyzed. the results demonstrated 143 differentially expressed proteins on treatment with scd-1. the expression of four proteins, namel ...201222533410
sago pith residue as an alternative cheap substrate for fermentable sugars production.sago pith residue is one of the most abundant lignocellulosic biomass which can serve as an alternative cheap substrate for fermentable sugars production. this residue is the fibrous waste left behind after the starch extraction process and contains significant amounts of starch (58%), cellulose (23%), hemicellulose (9.2%) and lignin (3.9%). the conversion of sago pith residue into fermentable sugars is commonly performed using cellulolytic enzymes or known as cellulases. in this study, crude ce ...201222528646
preclinical evaluation of two 68ga-siderophores as potential radiopharmaceuticals for aspergillus fumigatus infection imaging.invasive pulmonary aspergillosis is mainly caused by aspergillus fumigatus, and is one of the major causes of morbidity and mortality in immunocompromised patients. the mortality associated with invasive pulmonary aspergillosis remains high, mainly due to the difficulties and limitations in diagnosis. we have shown that siderophores can be labelled with (68)ga and can be used for pet imaging of a. fumigatus infection in rats. here we report on the further evaluation of the most promising (68)ga- ...201222526953
development of novel pcr assays to detect azole resistance-mediating mutations of the aspergillus fumigatus cyp51a gene in primary clinical samples from neutropenic patients.the increasing incidence of azole resistance in aspergillus fumigatus causing invasive aspergillosis (ia) in immunocompromised/hematological patients emphasizes the need to improve the detection of resistance-mediating cyp51a gene mutations from primary clinical samples, particularly as the diagnosis of invasive aspergillosis is rarely based on a positive culture yield in this group of patients. we generated primers from the unique sequence of the aspergillus fumigatus cyp51a gene to establish p ...201222526309
immediate hypersensitivity and serum ige antibody responses in patients with dermatophytosis.the association of dermatophytes with atopic patients and improvement in allergic signs with antifungal treatment suggest a possible link between chronic infection and atopy.201222523906
cd4(+) t cell vaccination overcomes defective cross-presentation of fungal antigens in a mouse model of chronic granulomatous disease.aspergillus fumigatus is a model fungal pathogen and a common cause of infection in individuals with the primary immunodeficiency chronic granulomatous disease (cgd). although primarily considered a deficiency of innate immunity, cgd is also linked to dysfunctional t cell reactivity. both cd4(+) and cd8(+) t cells mediate vaccine-induced protection from experimental aspergillosis, but the molecular mechanisms leading to the generation of protective immunity and whether these mechanisms are dysre ...201222523066
in vitro and in vivo role of heat shock protein 90 in amphotericin b resistance of aspergillus terreus.aspergillus terreus (a. terreus) is of serious concern because of a high propensity to dissemination and in vitro and in vivo resistance to amphotericin b (amb). the underlying molecular mechanism of amb is not known yet and here we want to explore whether fungal heat shock protein 90 (hsp90) is involved in polyene resistance in a. terreus. amb-susceptible (ats) and amb-resistant (atr) a. terreus and amb-susceptible aspergillus fumigatus (afs) were investigated in response to amb with a special ...201322515428
isolation of filamentous fungi from sputum in asthma is associated with reduced post-bronchodilator fev1.fungal sensitization is common in severe asthma, but the clinical relevance of this and the relationship with airway colonization by fungi remain unclear. the range of fungi that may colonize the airways in asthma is unknown.201222515394
germination of aspergillus fumigatus inside avian respiratory macrophages is associated with cytotoxicity.although aspergillosis is one of the most common diseases in captive birds, the pathogenesis of avian aspergillosis is poorly known. we studied the role of avian respiratory macrophages as a first line of defense against avian aspergillosis. the phagocytic and killing capacities of avian respiratory macrophages were evaluated using pigeon respiratory macrophages that were inoculated with aspergillus fumigatus conidia. on average, 25% of macrophage-associated conidia were phagocytosed after one h ...201222515231
transcriptional and proteomic analysis of the aspergillus fumigatus δprtt protease-deficient mutant.aspergillus fumigatus is the most common opportunistic mold pathogen of humans, infecting immunocompromised patients. the fungus invades the lungs and other organs, causing severe damage. penetration of the pulmonary epithelium is a key step in the infectious process. a. fumigatus produces extracellular proteases to degrade the host structural barriers. the a. fumigatus transcription factor prtt controls the expression of multiple secreted proteases. prtt shows similarity to the fungal gal4-type ...201222514608
identification of novel genes conferring altered azole susceptibility in aspergillus fumigatus.azoles are currently the mainstay of antifungal treatment both in agricultural and in clinical settings. although the target site of azole action is well studied, the basis of azole resistance and the ultimate mode of action of the drug in fungi are poorly understood. to gain a deeper insight into these aspects of azole action, restriction-mediated plasmid integration (remi) was used to create azole sensitive and resistant strains of the clinically important fungus aspergillus fumigatus. four az ...201222509997
towards the crystal structure elucidation of eukaryotic udp-galactopyranose mutase.udp-galactopyranose mutase (ugm) catalyzes the interconversion of udp-galactopyranose and udp-galactofuranose. eukaryotic ugms from aspergillus fumigatus and leishmania major have been purified to homogeneity by means of ni(2+)-affinity chromatography and crystallized. eukaryotic ugm structure elucidation was not straightforward owing to high pseudo-symmetry, twinning and very low anomalous signal. phasing to 2.8 å resolution using sad was successful for l. major ugm. however, the maps could onl ...201222505419
cytotoxicity and antimicrobial activity of the methanol extract and compounds from polygonum limbatum.the present study was designed to investigate the antimicrobial activity and the cytotoxicity of the methanol extract (pla) as well as fractions (pla1-4) and compounds [cardamomin (1), (±)-polygohomoisoflavanone (2), (s)-(-)-pinostrobin (3), 2',4'-dihydroxy-3',6'-dimethoxychalcone (4), (2s)-(-)-5-hydroxy-6,7-dimethoxyflavanone (5), and (2s)-(-)-5,7-dimethoxyflavanone (6)] obtained from leaves of polygonum limbatum. the microbroth dilution was used to determine the minimal inhibitory concentratio ...201222495442
a low-molecular-mass aspartic protease inhibitor from a novel penicillium sp.: implications in combating fungal infections.a low-molecular-mass aspartic protease inhibitor was isolated from a novel penicillium sp. the inhibitor was purified to homogeneity, as shown by reversed-phase hplc and sds-page. the m(r) of the inhibitor was 1585 and the amino acid composition showed the presence of d, d, d, e, a, k, l, y, h, i and w residues. the steady-state kinetic interactions of aspergillus saitoi aspartic protease with the inhibitor revealed the reversible, competitive, time-dependent tight-binding nature of the inhibito ...201222493301
genome-based cluster deletion reveals an endocrocin biosynthetic pathway in aspergillus fumigatus.endocrocin is a simple anthraquinone frequently identified in extracts of numerous fungi. several biosynthetic schemes for endocrocin synthesis have been hypothesized, but to date, no dedicated secondary metabolite gene cluster that produces this polyketide as its major metabolite has been identified. here we describe our biosynthetic and regulatory characterization of the endocrocin gene cluster in aspergillus fumigatus. this is the first report of this anthraquinone in this species. the biosyn ...201222492455
e-cadherin mediates adhesion and endocytosis of aspergillus fumigatus blastospores in human epithelial cells.aspergillus fumigatus (a. fumigatus) is a ubiquitous saprophytic fungus responsible for the majority of invasive mold infections in patients undergoing chemotherapy, organ transplantation or with persistent neutropenia. this study aimed to determine the role of e-cadherin for adhesion and endocytosis of a. fumigatus blastospores in the human epithelial cell line a549.201222490484
vanishing bronchus intermedius syndrome in a pediatric patient with cystic fibrosis after lung transplantation.airway complications occur frequently after lung transplantation. bronchial stenosis is the most frequently encountered complication with the most severe form of that being the vanishing bronchus intermedius syndrome (vbis). this rare disorder has never been reported in the pediatric population. this is the first report of vbis in a pediatric patient, specifically a 16-yr-old male patient with cystic fibrosis whose course was complicated by a lower airway infection with aspergillus fumigatus. th ...201222489792
chronic aspergillus fumigatus exposure upregulates the expression of mucin 5ac in the airways of asthmatic rats.airway mucus hypersecretion is associated with increased morbidity and mortality in patients with asthma. chronic aspergillus fumigatus (a. fumigatus) exposure leads to aggravation of airway inflammation and remodeling, including goblet cell hyperplasia (gch) and mucus hypersecretion in a rat model of asthma. the effects of chronic a. fumigatus exposure on the expression of airway mucin 5ac (muc5ac) are unknown.201222489685
systems biology of fungal infection.elucidation of pathogenicity mechanisms of the most important human-pathogenic fungi, aspergillus fumigatus and candida albicans, has gained great interest in the light of the steadily increasing number of cases of invasive fungal infections. a key feature of these infections is the interaction of the different fungal morphotypes with epithelial and immune effector cells in the human host. because of the high level of complexity, it is necessary to describe and understand invasive fungal infecti ...201222485108
recurrent fungal iris granuloma in a 10-year-old child.to report the diagnosis of a case of recurrent iris fungal granuloma presumed to be an iris tuberculoma in a 10-year-old girl.201222480141
invasive pulmonary aspergillosis due to a multi-azole resistant aspergillus fumigatus.a patient with invasive pulmonary aspergillosis due to an azole-resistant aspergillus fumigatus is described. despite treatment change from voriconazole to amphotericin b as soon as the resistance data were available, the patient died. azole resistance is an emerging problem, which significantly complicates the management of a. fumigatus infections. it should be considered in every patient with an invasive a. fumigatus infection who is not responding to voriconazole therapy.201622480040
dual role of nadp(h) in the reaction of a flavin dependent n-hydroxylating monooxygenase.aspergillus fumigatus siderophore a (af sida) is a flavin-dependent monooxygenase that catalyzes the hydroxylation of ornithine, producing n(5)-hydroxyornithine. this is the first step in the biosynthesis of hydroxamate-containing siderophores in a. fumigatus. af sida is essential for virulence, validating this enzyme as a drug target. af sida can accept reducing equivalents from either nadph or nadh and displays similar kinetic parameters when using either coenzyme. when the enzyme is reduced w ...201222465572
[pulmonary aspergillosis in a non-immunocompromised critically ill patient].in non-immunocompromised patients admitted to intensive care departments or units (icu), it is difficult to establish a definitive diagnosis of pulmonary aspergillosis because the signs and symptoms of this infectious disease are non-specific, and serological techniques are not very specific as well. for this reason, a diagnosis of possible pulmonary aspergillosis is initially established, and the starting of the treatment is controversial.201222463784
allergic bronchopulmonary aspergillosis with aspergilloma: an immunologically severe disease with poor outcome.the association between allergic bronchopulmonary aspergillosis (abpa) and aspergilloma has been proposed as a severe form of abpa. however, this conclusion is based on single-patient case reports. in this study, we describe the clinical details and immunological findings of this association and compare patients of abpa with aspergilloma and those without.201222457034
monitoring the reductive and oxidative half-reactions of a flavin-dependent monooxygenase using stopped-flow spectrophotometry.aspergillus fumigatus siderophore a (sida) is an fad-containing monooxygenase that catalyzes the hydroxylation of ornithine in the biosynthesis of hydroxamate siderophores that are essential for virulence (e.g. ferricrocin or n',n",n'''-triacetylfusarinine c). the reaction catalyzed by sida can be divided into reductive and oxidative half-reactions. in the reductive half-reaction, the oxidized fad bound to af sida, is reduced by nadph. in the oxidative half-reaction, the reduced cofactor reacts ...201222453826
chemotypic and genotypic diversity in the ergot alkaloid pathway of aspergillus fumigatus.aspergillus fumigatus is an opportunistic human pathogen that synthesizes a group of mycotoxins via a branch of the ergot alkaloid pathway. this fungus is globally distributed, and genetic data indicate that isolates recombine freely over that range; however, previous work on ergot alkaloids has focused on a limited number of isolates. we hypothesized that a. fumigatus harbors variation in the chemotype of ergot alkaloids and genotype of the ergot alkaloid gene cluster. analysis of 13 isolates b ...201522453123
conservation of nucleosome positions in duplicated and orthologous gene pairs.although nucleosome positions tend to be conserved in gene promoters, whether they are conserved in duplicated and orthologous genes is unknown. in order to elucidate how nucleosome positions are conserved between duplicated and orthologous gene pairs, i performed 2 comparative studies. first, i compared the nucleosome position profiles of duplicated genes in the filamentous ascomycete aspergillus fumigatus. after identifying 63 duplicated gene pairs among 9630 protein-encoding genes, i compared ...201222448128
hypoxia and fungal pathogenesis: to air or not to air?over the last 3 decades, the frequency of life-threatening human fungal infections has increased as advances in medical therapies, solid-organ and hematopoietic stem cell transplantations, an increasing geriatric population, and hiv infections have resulted in significant rises in susceptible patient populations. although significant advances have been made in understanding how fungi cause disease, the dynamic microenvironments encountered by fungi during infection and the mechanisms by which th ...201222447924
serologic allergic bronchopulmonary aspergillosis (abpa-s): long-term outcomes.abpa is radiologically classified on the presence or absence of central bronchiectasis (cb) as abpa-cb and serologic abpa (abpa-s) respectively. few studies have described the follow-up of patients with abpa-s. the aim of this retrospective study was to describe the outcomes of abpa-s.201222445696
aspergillus fumigatus mitochondrial electron transport chain mediates oxidative stress homeostasis, hypoxia responses and fungal pathogenesis.we previously observed that hypoxia is an important component of host microenvironments during pulmonary fungal infections. however, mechanisms of fungal growth in these in vivo hypoxic conditions are poorly understood. here, we report that mitochondrial respiration is active in hypoxia (1% oxygen) and critical for fungal pathogenesis. we generated aspergillus fumigatus alternative oxidase (aoxa) and cytochrome c (cyca) null mutants and assessed their ability to tolerate hypoxia, macrophage kill ...201222443190
expression, purification and crystallization of an indole prenyltransferase from aspergillus fumigatus.cdpnpt from aspergillus fumigatus is a dimethylallyltryptophan synthase/indole prenyltransferase that catalyzes reverse prenylation at position n1 of tryptophan-containing cyclic dipeptides. residues 38-440 of cdpnpt were expressed in escherichia coli and crystallized using the sitting-drop vapour-diffusion and microseeding techniques. the crystals belonged to space group p2(1)2(1)2(1), with unit-cell parameters a = 84.4, b = 157.1, c = 161.8 å, α = β = γ = 90.0°.201222442243
synthesis of a new group of aliphatic hydrazide derivatives and the correlations between their molecular structure and biological activity.in view of the growing demand for new compounds showing biological activity against pathogenic microorganisms, such as pathogenic and phytopathogenic fungi, the objective of this study was to synthesize a new group of aliphatic and aromatic derivatives of hydrazide. in consequence of the reactions observed during synthesis, the resulting compounds retained their linear structure. their structure and lipophilicity, measured by high-performance liquid chromatography (hplc), were analyzed. correlat ...201222441334
targeting the oxidative stress response system of fungi with redox-potent chemosensitizing agents.the cellular antioxidant system is a target in the antifungal action of amphotericin b (amb) and itraconazole (itz), in filamentous fungi. the sakaδ mutant of aspergillus fumigatus, a mitogen-activated protein kinase (mapk) gene deletion mutant in the antioxidant system, was found to be more sensitive to amb or itz than other a. fumigatus strains, a wild type and a mpkcδ mutant (a mapk gene deletion mutant in the polyalcohol sugar utilization system). complete fungal kill (≥99.9%) by itz or amb ...201222438852
disinfection of ocular cells and tissues by atmospheric-pressure cold plasma.low temperature plasmas have been proposed in medicine as agents for tissue disinfection and have received increasing attention due to the frequency of bacterial resistance to antibiotics. this study explored whether atmospheric-pressure cold plasma (apcp) generated by a new portable device that ionizes a flow of helium gas can inactivate ocular pathogens without causing significant tissue damage.201222432007
a potent plant-derived antifungal acetylenic acid mediates its activity by interfering with fatty acid homeostasis.6-nonadecynoic acid (6-nda), a plant-derived acetylenic acid, exhibits strong inhibitory activity against the human fungal pathogens candida albicans, aspergillus fumigatus, and trichophyton mentagrophytes. in the present study, transcriptional profiling coupled with mutant and biochemical analyses were conducted using the model yeast saccharomyces cerevisiae to investigate its mechanism of action. 6-nda elicited a transcriptome response indicative of fatty acid stress, altering the expression o ...201222430960
invasive aspergillosis in a putty-nosed monkey (cercopithecus nictitans) with adrenocortical cushing's syndrome.an 18-year-old captive female putty-nosed-monkey (cercopithecus nictitans) with a history of long-term infertility and hyperglucocorticism was euthanized because of perforating thoracic trauma induced by group members and subsequent development of neurological signs.201222429114
phage display against corneal epithelial cells produced bioactive peptides that inhibit aspergillus adhesion to the corneas.dissection of host-pathogen interactions is important for both understanding the pathogenesis of infectious diseases and developing therapeutics for the infectious diseases like various infectious keratitis. to enhance the knowledge about pathogenesis infectious keratitis, a random 12-mer peptide phage display library was screened against cultured human corneal epithelial cells (hcec). fourteen sequences were obtained and blastp analysis showed that most of their homologue counterparts in genban ...201222428072
new antifungal compounds from aspergillus terreus isolated from desert soil.two new butyrolactone i derivatives: 3-[3-hydroxy-4-(3-methyl-but-2-enyl)-phenyl]-5-(-4-hydroxybenzyl)-4-methyl-dihydrofuran-2(3h)-one (1) and (z)-3-[3-hydroxy-4-(3-methyl-but-2-enyl)-phenyl]-5-(-4-hydroxybenzylidene)-4-methyl-dihydrofuran-2(3h)-one (2), in addition to the previously described (s)-methyl-4-hydroxy-2-[4-hydroxy-3-(3-methyl-but-2-enyl)-benzyl]-3-(4-hydroxy-phenyl)-5-oxo-2,5-dihydro-furan-2-carboxylic acid methyl ester (3), were identified from a strain of aspergillus terreus thom ...201222422648
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