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the developmental regulators, flbb and flbe, are involved in the virulence of aspergillus fumigatus.several upstream activators required for proper activation of brla are involved in the development, vegetative growth, toxin production, and pathogenesis of aspergillus fumigatus. in this study, we characterized the roles of two upstream developmental regulators, a. fumigatus flbb (afuflbb) and flbe (afuflbe), in toxin production and virulence. the deletion of afuflbb and afuflbe resulted in reduction of the expression of afulaea. moreover, only about 8% to 10% of fumagillin was produced in the ...201323676908
effects of chirality on the antifungal potency of methylated succinimides obtained by aspergillus fumigatus biotransformations. comparison with racemic ones.eighteen (3r) and (3r,4r)-n-phenyl-, n-phenylalkyl and n-arylsuccinimides were prepared with high enantioselectivity by biotransformation of maleimides with a. fumigatus. this environmentally friendly, clean and economical procedure was performed by the whole-cell fungal bioconversion methodology. their corresponding eighteen racemic succinimides were prepared instead by synthetic methods. both, the racemic and the chiral succinimides were tested simultaneously by the microbroth dilution method ...201323676473
rsma regulates aspergillus fumigatus gliotoxin cluster metabolites including cyclo(l-phe-l-ser), a potential new diagnostic marker for invasive aspergillosis.dimeric basic leucine zipper (bzip) proteins are conserved transcriptional enhancers found in all eukaryotes. a recently reported and novel function for bzips is association of these proteins with secondary metabolite production in filamentous fungi. in particular a yap-like bzip termed rsma (restorer of secondary metabolism a) was identified in aspergillus nidulans that positively regulates the carcinogen sterigmatocystin. to assess for conserved function for rsma, we examined a role of this pr ...201323671611
cyp51a-based mechanisms of aspergillus fumigatus azole drug resistance present in clinical samples from germany.since the mid-1990s, a steady increase in the occurrence of itraconazole-resistant aspergillus fumigatus isolates has been observed in clinical contexts, leading to therapeutic failure in the treatment of aspergillosis. this increase has been predominantly linked to a single allele of the cyp51a gene, termed tr/l98h, which is thought to have arisen through the use of agricultural azoles. here, we investigated the current epidemiology of triazole-resistant a. fumigatus and underlying cyp51a mutat ...201323669382
population-based survey of filamentous fungi and antifungal resistance in spain (filpop study).a population-based survey was conducted to investigate the epidemiology of and antifungal resistance in spanish clinical strains of filamentous fungi isolated from deep tissue samples, blood cultures, and respiratory samples. the study was conducted in two different periods (october 2010 and may 2011) to analyze seasonal variations. a total of 325 strains were isolated in 29 different hospitals. the average prevalence was 0.016/1,000 inhabitants [corrected]. strains were identified by sequencing ...201323669377
environmental study of azole-resistant aspergillus fumigatus with tr34/l98h mutations in the cyp51a gene in iran.azole resistance in aspergillus is emerging in european and asian countries. as azoles are mainstay of therapy in the management of aspergillosis, azole resistance has serious implications in patient management. we report the emergence of resistance to triazoles in environmental aspergillus fumigatus isolates in iran. the tr34/l98h mutation was the only resistance mechanism. overall 3.3% of the a. fumigatus isolates from hospital surroundings in sari and tehran had the same tr34/l98h straf genot ...201323668594
voriconazole resistance in aspergillus fumigatus: should we be concerned? 201323667265
aspergillosis due to voriconazole highly resistant aspergillus fumigatus and recovery of genetically related resistant isolates from domiciles.azole resistance is an emerging problem in aspergillus fumigatus and complicates the management of patients with aspergillus-related diseases. selection of azole resistance may occur through exposure to azole fungicides in the environment. in the netherlands a surveillance network was used to investigate the epidemiology of resistance selection in a. fumigatus.201323667263
crude cellulase from oil palm empty fruit bunch by trichoderma asperellum upm1 and aspergillus fumigatus upm2 for fermentable sugars production.cellulase is an enzyme that converts the polymer structure of polysaccharides into fermentable sugars. the high market demand for this enzyme together with the variety of applications in the industry has brought the research on cellulase into focus. in this study, crude cellulase was produced from oil palm empty fruit bunch (opefb) pretreated with 2% naoh with autoclave, which was composed of 59.7% cellulose, 21.6% hemicellulose, and 12.3% lignin using trichoderma asperellum upm1 and aspergillus ...201323666614
evaluation of pharmacological activities, cytotoxicity and phenolic composition of four maytenus species used in southern african traditional medicine to treat intestinal infections and diarrhoeal diseases.microbial infections and resulting inflammation and oxidative stress are common pathogenesis of gastrointestinal tract (git) disorders. in south africa, several species of the genus maytenus are used in traditional medicine to treat various infectious diseases. most of the previous work on this genus was focused on nonpolar extracts from the root and bark. in this study, leaf extracts of polar extracts of maytenus peduncularis, maytenus procumbens, maytenus senegalensis and maytenus undata were ...201323663902
cardiac device-related invasive aspergilloma assessed by live/real time three-dimensional transthoracic echocardiography.cardiac device-related infection caused by aspergillus species is a rare finding associated with high mortality. prompt recognition and treatment is imperative, but difficult as blood cultures are often negative and diagnosis requires a high index of suspicion. live/real time three-dimensional transthoracic echocardiography (3dtte) provides incremental knowledge in the characterization of valvular vegetations. here, we provide a detailed description of an invasive cardiac device-related infectio ...201323662919
[preliminary study on aspergillus fumigatus-induced ikkα controlled maspin protein expression in respiratory epithelial cells of rats].to study if the expression of maspin protein in respiratory epithelial cells was downregulated through iκb kinase-α (ikkα)-controlled mechanism in an aspergillus fumigatus-induced model in rat.201323656816
invasive fungal infections in patients with chronic granulomatous disease.invasive fungal infections are a major threat for chronic granulomatous disease (cgd) patients. the present study provides a comprehensive overview of published invasive fungal infections in the cgd host through an extensive review of epidemiological, clinical, diagnostic and therapeutic data. in addition to the often mild clinical presentation, the currently used diagnostics for invasive aspergillosis have low sensitivity in cgd patients and cannot be easily translated to this non-neutropenic h ...201323654055
modified culture method detects a high diversity of fungal species in cystic fibrosis patients.cystic fibrosis (cf) is one of the most common genetic lung diseases worldwide. the production of sticky viscous mucus leads to enhanced bacterial colonization and infection, but yeasts and filamentous fungi are also found abundantly in the mucus of patients suffering from cf. the role of fungi in the airways of cf patients is still not understood completely. furthermore, recent investigations have shown that the spectrum of fungi isolated from the airways of cf patients depends strongly on the ...201423651180
inflammatory marker profiles in an avian experimental model of aspergillosis.aspergillosis is a common infection in avian species, but can be a challenge to diagnose. inflammatory markers have been successfully used in mammals for diagnostic and monitoring purposes of various diseases. the aim of this study was to identify inflammatory markers that could aid in the diagnosis of aspergillosis in an avian species. five-week-old japanese quail were infected experimentally with aspergillus fumigatus, and inflammatory markers were measured in plasma. in addition, lung tissues ...201323651177
n-glycosylation of gel1 or gel2 is vital for cell wall β-glucan synthesis in aspergillus fumigatus.fungal cell wall is a dynamic structure that communicates with and protects the cell from outside stress. in aspergillus fumigatus, the cell wall β-glucans are mainly elongated by β-1,3-glucanosyltransferases gels, which consist of seven family members (gel1-7) utilizing β-1,3-glucan chains as substrates. previously, we have shown that the mutant deficient of n-glycan processing displays a reduction in the cell wall β-glucans, suggesting that n-glycosylation is required for the proper function o ...201323650256
bacterium induces cryptic meroterpenoid pathway in the pathogenic fungus aspergillus fumigatus.stimulating encounter: the intimate, physical interaction between the soil-derived bacterium streptomyces rapamycinicus and the human pathogenic fungus aspergillus fumigatus led to the activation of an otherwise silent polyketide synthase (pks) gene cluster coding for an unusual prenylated polyphenol (fumicycline a). the meroterpenoid pathway is regulated by a pathway-specific activator gene as well as by epigenetic factors.201323649940
a point mutation in ftmd blocks the fumitremorgin biosynthetic pathway in aspergillus fumigatus strain af293.fumitremorgins (ftms), tremorgenic mycotoxins produced by the human pathogen aspergillus fumigatus, are prenylated indole alkaloids that have been extensively studied in view of their diverse chemical structures and biological activities. their biosynthetic gene (ftm) cluster was identified on the basis of the genome sequence of a. fumigatus. however, it has been reported that the ftm cluster in genome reference strain af293 is inactive, which makes complete understanding of the ftm pathway diff ...201323649274
proteomic analysis of temperature dependent extracellular proteins from aspergillus fumigatus grown under solid-state culture condition.fungal species of the genus aspergillus are filamentous ubiquitous saprophytes that play a major role in lignocellulosic biomass recycling and also are considered as cell factories for the production of organic acids, pharmaceuticals, and industrially important enzymes. analysis of extracellular secreted biomass degrading enzymes using complex lignocellulosic biomass as a substrate by solid-state fermentation could be a more practical approach to evaluate application of the enzymes for lignocell ...201323647126
opportunistic infection of aspergillus and bacteria in captive cape vultures (gyps coprotheres).to describe clinical signs, pathology, diagnosis and treatment of cape vultures in which aspergillus fumigatus (a. fumigatus) and mixed species of bacteria were isolated.201323646305
aspergillus fumigatus-induced il-22 is not restricted to a specific th cell subset and is dependent on complement receptor 3.th cell responses induced by aspergillus fumigatus have been extensively investigated in mouse models. however, the requirements for differentiation and the characteristics of a. fumigatus-induced human th cell subsets remain poorly defined. we demonstrate that a. fumigatus induces th1 and th17 subsets in human pbmcs. moreover, we show that the cytokine il-22 is not restricted to a specific th subset, in contrast to il-17a. the pattern recognition and cytokine pathways that skew these aspergillu ...201323645883
x-ray structure analysis and characterization of afuei, an elastase inhibitor from aspergillus fumigatus.elastase from aspergillus sp. is an important factor for aspergillosis. afuei is an inhibitor of the elastase derived from aspergillus fumigatus. afuei is a member of the i78 inhibitor family and has a high inhibitory activity against elastases of aspergillus fumigatus and aspergillus flavus, human neutrophil elastase and bovine chymotrypsin, but does not inhibit bovine trypsin. here we report the crystal structure of afuei in two crystal forms. afuei is a wedge-shaped protein composed of an ext ...201323640894
synthesis and antifungal activity of the novel triazole derivatives containing 1,2,3-triazole fragment.a series of fluconazole analogues containing 1,2,3-triazole fragment have been designed and synthesized on the basis of the active site of the cytochrome p450 14α-demethylase (cyp51). their structures were characterized by (1)h nmr, (13)c nmr and lc-ms. the mic80 values indicate that the target compounds 1a-r showed higher activities against nearly all the fungi tested to some extent except against aspergillus fumigatus. compounds 1c, e, f, l and p showed 128 times higher activity (with the mic8 ...201323640383
loss of ccla, required for histone 3 lysine 4 methylation, decreases growth but increases secondary metabolite production in aspergillus fumigatus.secondary metabolite (sm) production in filamentous fungi is mechanistically associated with chromatin remodeling of specific sm clusters. one locus recently shown to be involved in sm suppression in aspergillus nidulans was ccla, a member of the histone 3 lysine 4 methylating compass complex. here we examine loss of ccla and a putative h3k4 demethylase, hdma, in the human pathogen aspergillus fumigatus. although deletion of hdma showed no phenotype under the conditions tested, the ccla deletant ...201323638376
pretreatment with tlr2 and tlr4 ligand modulates innate immunity in corneal fibroblasts challenged with aspergillus fumigatus.to study the innate immunity in telomerase-immortalized human stroma fibroblasts (thsfs) challenged with aspergillus fumigatus hyphae after copretreatment with tlr2 and tlr4 ligand.201323633661
light sensing in aspergillus fumigatus highlights the case for establishing new models for fungal photobiology.microbes inhabit diverse environmental locations, and many species need to shift their physiology between different niches. to do this effectively requires the accurate sensing of and response to the environment. for pathogens, exposure to light is one major change between a free-living saprophyte lifestyle and causation of disease within the host. however, how light may act as a signal to influence pathogenesis, on the side of either the host or the pathogen, is poorly understood. research duri ...201323631920
is azole resistance in aspergillus fumigatus a problem in spain?aspergillus fumigatus complex comprises a. fumigatus and other morphologically indistinguishable cryptic species. we retrospectively studied 362 a. fumigatus complex isolates (353 samples) from 150 patients with proven or probable invasive aspergillosis or aspergilloma (2, 121, and 6 samples, respectively) admitted to the hospital from 1999 to 2011. isolates were identified using the β-tubulin gene, and only 1 isolate per species found in each sample was selected. antifungal susceptibility to az ...201323629706
antifungal indole and pyrrolidine-2,4-dione derivative peptidomimetic lead design based on in silico study of bioactive peptide families.the rise of opportunistic fungal infections highlights the need for development of new antimicrobial agents. antimicrobial peptides (amps) and antifungal peptides (afps) are among the agents with minimal resistance being developed against them, therefore they can be used as structural templates for design of new antimicrobial agents.201323626876
1,1-diphenyl,2-picrylhydrazyl free radical scavenging, bactericidal, fungicidal and leishmanicidal properties of teucrium stocksianum.in the present study, we evaluated the pharmacological and toxicological effects of teucrium stocksianum. the crude extract of t. stocksianum (ts.cr) and its subsequent organic fractions: n-hexane (ts.hex), chloroform (ts.chcl3) and ethyl acetate (ts.etac) exhibited 1,1-diphenyl,2-picrylhydrazyl free radical scavenging activity with different potencies. ts.etac was found to be most potent. ts.cr, ts.hex, ts.chcl3 and ts.etac showed significant bactericidal activity against escherichia coli, stap ...201523625908
clinical and pathological findings of concurrent poxvirus lesions and aspergillosis infection in canaries.to investigate clinical, pathological and mycological findings in canaries, in which pox lesions and aspergillus fumigatus (a. fumigatus) infection were observed simultaneously.201323620834
fungal siderophore biosynthesis is partially localized in peroxisomes.siderophores play a central role in iron metabolism and virulence of most fungi. both aspergillus fumigatus and aspergillus nidulans excrete the siderophore triacetylfusarinine c (tafc) for iron acquisition. in a. fumigatus, green fluorescence protein-tagging revealed peroxisomal localization of the tafc biosynthetic enzymes sidi (mevalonyl-coa ligase), sidh (mevalonyl-coa hydratase) and sidf (anhydromevalonyl-coa transferase), while elimination of the peroxisomal targeting signal (pts) impaired ...201323617799
β-1,3-glucan modifying enzymes in aspergillus fumigatus.in aspergillus fumigatus like in other filamentous ascomycetes, β-1,3-glucan constitutes a prominent cell wall component being responsible for rigidity of the cell wall structure. in filamentous fungi, softening of the cell wall is absolutely required during conidial germination and hyphal branching. because of the central structure of β-1,3-glucans, it is expected that β-1,3-glucanases play a major role in cell wall softening. based on in silico and experimental data, this review gives an overv ...201323616783
environmental fungicides and triazole resistance in aspergillus.fungal diseases are problematic in both human health and agriculture. treatment options are limited and resistance may emerge. the relatively recent recognition of triazole resistance in aspergillus fumigatus has prompted questioning of the origin of resistance. while multiple mechanisms are described in clinical isolates from triazole-treated patients, some de novo resistance is also recognised, especially attributable to tr34 /l98h. such strains probably arose in the environment, and, indeed, ...201423616354
a 76-year-old man with a right lung adenocarcinoma and invasive aspergillosis.a 76-year-old male with adenocarcinoma on the right lung underwent five cycles of chemotherapy with pemetrexed disodium, cisplatin, and dexamethasone. imaging studies of control showed a node in a cavitary lesion on the left lung, and the main hypothesis was aspergillus infection. pcr was utilized and contributed to establish the early diagnosis in this patient with invasive aspergillosis. furthermore, the species aspergillus fumigatus was characterized by its growing at 50 °c but not at 10 °c, ...201323615821
production, purification, and characterization of exoglucanase by aspergillus fumigatus.fungi are considered good producers of industrially valuable enzymes with higher enzymatic activities. among these cellulases are group of extracellular enzymes commonly employed in many industries for the hydrolysis of cellulolytic material. aspergillus fumigatus produced exoglucanase having high enzymatic activity (83 u/gds) during the solid-state fermentation of wheat straw under optimum physical and nutritional conditions. maximum production was obtained after 72 h of fermentation, at 55 °c ...201323615734
[construction of a cell-surface expression system in trichoderma reesei].afmp1p is a glycosylphosphatidylinositol (gpi) anchored cell wall protein (gpi-cwp) identified in filamentous fungus aspergillus fumigatus, which contains a specific c terminal signal for cell wall localization. trichoderma reesei is known as a safe fungal species (gras) and widely used in the industry. thus, developing of the cell-surface expression systems in t. reesei is of industrial interest.201323614239
functional properties of a manganese-activated exo-polygalacturonase produced by a thermotolerant fungus aspergillus niveus.a thermotolerant fungus identified as aspergillus niveus was isolated from decomposing materials and it has produced excellent levels of hydrolytic enzymes that degrade plant cell walls. a. niveus germinated faster at 40 °c, presenting protein levels almost twofold higher than at 25 °c. the crude extract of the a. niveus culture was purified by diethylaminoethyl (deae)-cellulose, followed by biogel p-100 column. polygalacturonase (pg) is a glycoprotein with 37.7 % carbohydrate, molecular mass of ...201323613286
new trifluoromethyl quinolone derivatives: synthesis and investigation of antimicrobial properties.a series of quinolone derivatives, containing different heterocyclic amines were prepared. synthesized compounds were evaluated for their in vitro antimicrobial activities against two gram-positive bacteria, three gram-negative bacteria as well as four fungi. all the derivatives showed good activity towards gram-positive bacteria and less activity towards gram-negative bacteria. they also showed moderate to comparable activity against aspergillus niger and candida albicans and low to moderate an ...201323611733
multiple endobronchial mycetomas with varied appearances and mixed fungal flora.we present images of a patient with multiple endobronchial mycetomas visible by bronchoscopy with varying appearances and with mixed fungal flora on culture. a 44-year-old african american male previously treated for pulmonary tuberculosis 11 years earlier presented with moderate hemoptysis and infiltrates in the right upper lobe on chest radiograph. he received levofloxacin without improvement in the infiltrate. computed tomography scan revealed bronchiectasis, multiple intrabronchial masses, a ...201323609249
mycotoxin production by pure fungal isolates analysed by means of an uhplc-ms/ms multi-mycotoxin method with possible pitfalls and solutions for patulin-producing isolates.this study is the first report of applying an ultra high performance liquid chromatography/tandem mass spectrometric (uhplc-ms/ms) multi-mycotoxin method to identify and quantify the mycotoxins produced by pure fungal isolates grown on yeast extract sucrose (yes) agar. the method developed concerns a triple extraction procedure based on methanol, dichloromethane and ethyl acetate. the total extract was chromatographically separated on an uhplc beh c18 column and analyzed with a triple quadrupole ...201123605621
gliotoxin in aspergillus fumigatus: an example that mycotoxins are potential virulence factors.moulds produce several different mycotoxins that may improve their chance of survival in particular environments. for example, aspergillus fumigatus, an important human pathogen, produces several mycotoxins including gliotoxin. this secondary metabolite, a small lipid soluble dipeptide, exerts toxic effects on phagocytic cells and t-lymphocytes at low concentrations in vitro. a. fumigatus also produces high levels of gliotoxin in vivo, and this suggests that host defense mechanisms might be impa ...200923605091
expression of the protein serum amyloid a in response to aspergillus fumigatus in murine models of allergic airway inflammation.serum amyloid a (saa) is an acute phase protein that is elevated in blood during inflammation. the role of this protein in allergic diseases of airways remains unclear.201523603100
secondary metabolites from the endophytic fungi penicillium polonicum and aspergillus fumigatus.two new compounds, rhodostegone (1) from endophytic fungus penicillium polonicum and cyclo-(l-val-l-leu) (2) from aspergillus fumigatus, together with six known diketopiperazines (3-8), were isolated. the structures of these compounds were characterized through a combination of extensive ir, ms, nmr, and cd analysis.201323600807
disparate proteome responses of pathogenic and nonpathogenic aspergilli to human serum measured by activity-based protein profiling (abpp).aspergillus fumigatus is the primary pathogen causing the devastating pulmonary disease invasive aspergillosis in immunocompromised individuals. there is high genomic synteny between a. fumigatus and closely related rarely pathogenic neosartorya fischeri and aspergillus clavatus genomes. we applied activity-based protein profiling to compare unique or overexpressed activity-based probe-reactive proteins of all three fungi over time in minimal media growth and in response to human serum. we found ...201323599423
aspergillus fumigatus during stable state and exacerbations of copd.bacteria are often isolated in stable chronic obstructive pulmonary disease (copd). whether fungi are also commonly present and associated with clinical and pathological features of disease is uncertain. we investigated the frequency of filamentous fungal culture and ige sensitisation to aspergillus fumigatus and the relationship to clinical outcomes in copd subjects. copd subjects were recruited to enter a 1-year observational study. assessments of lung function, allergen testing and sputum ana ...201423598955
itraconazole as 'bridge therapy' to anti-ige in a patient with severe asthma with fungal sensitisation.sensitisation to fungi has been reported to play an important role in a particular phenotype of severe asthma, the so-called severe asthma with fungal sensitisation, characterised by high levels of total ige, which may be an obstacle to anti-ige therapy. we describe here the case of a polysensitised woman with refractory asthma, sensitised to aspergillus fumigatus with high total ige values (1793 kua/l), but without the diagnostic criteria for allergic bronchopulmonary aspergillosis. additional ...201323598928
antimicrobial potential of ricinus communis leaf extracts in different solvents against pathogenic bacterial and fungal strains.to investigate the in vitro antimicrobial activities of the leaf extract in different solvents viz., methanol, ethanol and water extracts of the selected plant ricinus communis.201223593573
low-volume toolbox for the discovery of immunosuppressive fungal secondary metabolites.the secondary metabolome provides pathogenic fungi with a plethoric and versatile panel of molecules that can be deployed during host ingress. while powerful genetic and analytical chemistry methods have been developed to identify fungal secondary metabolites (sms), discovering the biological activity of sms remains an elusive yet critical task. here, we describe a process for identifying the immunosuppressive properties of aspergillus sms developed by coupling a cost-effective microfluidic neut ...201323592999
assessment of efficacy of antifungals against aspergillus fumigatus: value of real-time bioluminescence imaging.aspergillus fumigatus causes life-threatening infections, especially in immunocompromised patients. common drugs for therapy of aspergillosis are polyenes, azoles, and echinocandins. however, despite in vitro efficacy of these antifungals, treatment failure is frequently observed. in this study, we established bioluminescence imaging to monitor drug efficacy under in vitro and in vivo conditions. in vitro assays confirmed the effectiveness of liposomal amphotericin b, voriconazole, and anidulafu ...201323587947
exposure assessment of lovastatin in pu-erh tea.this paper reports the results of an extensive survey on the levels of lovastatin in pu-erh tea samples. the microbial source of lovastatin was assessed by testing the ability of fungi with higher isolation frequency in the pu-erh tea samples to produce lovastatin on czapek yeast extract agar (cya). lovastatin was not detected in any of the raw pu-erh tea samples without storage but was found in almost all the ripe pu-erh tea samples, with lovastatin contents ranging from 20.61 ng/gdw to 226.38 ...201323587710
one single basic amino acid at the ω-1 or ω-2 site is a signal that retains glycosylphosphatidylinositol-anchored protein in the plasma membrane of aspergillus fumigatus.although the plasma membrane is the terminal destination for glycosylphosphatidylinositol (gpi) proteins in higher eukaryotes, cell wall-attached gpi proteins (gpi-cwps) are found in many fungal species. in yeast, some of the cis-requirements directing localization of gpi proteins to the plasma membrane or cell wall are now understood. however, it remains to be determined how aspergillus fumigatus, an opportunistic fungal pathogen, signals, and sorts gpi proteins to either the plasma membrane or ...201323584992
the cdr1b efflux transporter is associated with non-cyp51a-mediated itraconazole resistance in aspergillus fumigatus.recent increases in triazole resistance in aspergillus fumigatus have been attributed primarily to target site (cyp51a) mutations. a recent survey of resistant isolates in manchester showed that >50% of resistant isolates had no mutation in cyp51a or its promoter. we investigated the mechanisms of resistance in clinical azole-resistant isolates without cyp51a mutations.201323580559
clinical-scale generation of multi-specific anti-fungal t cells targeting candida, aspergillus and mucormycetes.invasive fungal infections, in particular, infections caused by candida, aspergillus and mucormycetes, are a major cause of morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation. adoptive transfer of donor-derived anti-fungal t cells shows promise to restore immunity and to offer a cure. because t cells recognize only specific epitopes, the low rate of patients in which the causal fungal pathogen can be identified and the considerable number of patient ...201323579059
active site model of (r)-selective ω-transaminase and its application to the production of d-amino acids.ω-transaminase (ω-ta) is one of the important biocatalytic toolkits owing to its unique enzyme property which enables the transfer of an amino group between primary amines and carbonyl compounds. in addition to preparation of chiral amines, ω-ta reactions have been exploited for the asymmetric synthesis of l-amino acids using (s)-selective ω-tas. however, despite the availability of (r)-selective ω-tas, catalytic utility of the ω-tas has not been explored for the production of d-amino acids. her ...201423576035
volatile composition and antimicrobial activity of the essential oil of artemisia absinthium growing in western ghats region of north west karnataka, india.artemisia absinthium l. (asteraceae) is an aromatic, herbaceous, perennial plant commonly known as wormwood. artemisia absinthium is traditionally used as an anthelmintic, antiseptic, antispasmodic and for bacillary dysentery, cancers and neurodegenerative diseases.201323570523
changes in atmospheric co2 influence the allergenicity of aspergillus fumigatus.increased susceptibility to allergies has been documented in the western world in recent decades. however, a comprehensive understanding of its causes is not yet available. it is therefore essential to understand trends and mechanisms of allergy-inducing agents, such as fungal conidia. in this study, we investigated the hypothesis that environmental conditions linked to global atmospheric changes can affect the allergenicity of aspergillus fumigatus, a common allergenic fungal species in indoor ...201323568517
characterization of homocysteine γ-lyase from submerged and solid cultures of aspergillus fumigatus ash (jx006238).among 25 isolates, aspergillus fumigatus ash (jx006238) was identified as a potent producer of homocysteine gamma- lyase. the nutritional requirements to maximize the enzyme yield were optimized under submerged (sf) and solid-state fermentation (ssf) conditions, resulting in a 5.2- and 2.3-fold increase, respectively, after the last purification step. the enzyme exhibited a single homogenous band of 50 kda on sds-page, along with an optimum ph of 7.8 and ph stability range of 6.5 to 7.8. it also ...201323568204
design, synthesis and antimicrobial activity of novel benzothiazole analogs.in an attempt to design and synthesize a new class of antimicrobials, dialkyne substituted 2-aminobenzothiazole was reacted with various substituted aryl azides to generate a small library of 20 compounds (3a-t) by click chemistry. structures of the newly synthesized compounds were established on the basis of spectral data. these compounds were screened for their antibacterial activity against gram+ bacteria (staphylococcus aureus and enterococcus faecalis), gram- bacteria (salmonella typhi, esc ...201323567952
chlorine gas exposure increases susceptibility to invasive lung fungal infection.chlorine (cl₂) is a highly irritating and reactive gas with potential occupational and environmental hazards. acute exposure to cl₂ induces severe epithelial damage, airway hyperreactivity, impaired alveolar fluid clearance, and pulmonary edema in the presence of heightened inflammation and significant neutrophil accumulation in the lungs. herein, we investigated whether cl₂ exposure affected the lung antimicrobial immune response leading to increased susceptibility to opportunistic infections. ...201323564508
pathway of glycine betaine biosynthesis in aspergillus fumigatus.the choline oxidase (choa) and betaine aldehyde dehydrogenase (badh) genes identified in aspergillus fumigatus are present as a cluster specific for fungal genomes. biochemical and molecular analyses of this cluster showed that it has very specific biochemical and functional features that make it unique and different from its plant and bacterial homologs. a. fumigatus choap catalyzed the oxidation of choline to glycine betaine with betaine aldehyde as an intermediate and reduced molecular oxygen ...201323563483
structure-activity relationship of cytochrome bc1 reductase inhibitor broad spectrum antifungal ilicicolin h.ilicicolin h is a broad spectrum antifungal agent showing sub micro g/ml mics against candida spp., aspergillus fumigatus and cryptococcus spp. it is a potent inhibitor (c50 2-3ng/ml) of the mitochondrial cytochrome bc1 reductase with over 1000-fold selectivity against rat liver cytochrome bc1 reductase. structure-activity relationship of semisynthetic derivatives by chemical modification of ilicicolin h and its 19-hydroxy derivative produced by biotransformation have been described. basic 4'-es ...201323562597
azole resistant aspergillus fumigatus: an emerging problem.azole resistance has appeared recently in aspergillus fumigatus and increased dangerously in the last decade. the main resistance mechanism is a point mutation of cyp51a, the gene encoding 14α-sterol demethylase, the target enzyme of azole antifungal drugs. this mutation can induce resistance to itraconazole alone or multi-azole resistance. cyp51a mutation can occur in two cases. the first usually concerns patients receiving long-term azole therapy, most of the time for chronic aspergillosis, an ...201323562488
deciphering the aetiology of a mixed fungal infection by broad-range pcr with sequencing and fluorescence in situ hybridisation.simultaneous infections with multiple fungi may be misinterpreted as monomicrobial infections by current diagnostics with ramifications for the choice of antimicrobial agents that may impact patient outcomes. the application of molecular methods on tissue samples may be useful to decipher the aetiology of mixed fungal infections. we present a leukaemic patient who died from sepsis due to candidaemia. the postmortem examination documented fungal elements in lung tissue. fungal dna was amplified f ...201323560622
reconstruction of the biosynthetic pathway for the core fungal polyketide scaffold rubrofusarin in saccharomyces cerevisiae.fungal polyketides include commercially important pharmaceuticals and food additives, e.g. the cholesterol-lowering statins and the red and orange monascus pigments. presently, production relies on isolation of the compounds from the natural producers, and systems for heterologous production in easily fermentable and genetically engineerable organisms, such as saccharomyces cerevisiae and escherichia coli are desirable. rubrofusarin is an orange polyketide pigment that is a common intermediate i ...201323557488
biological activities of selected basidiomycetes from yemen.in a previous paper we demonstrated the results of biological screening of yemeni basidiomycetes. the present study was aimed to investigate the antimicrobial and the antioxidant activity of further basidiomycetes collected in yemen. dichloromethane, methanol and aqueous extracts of the fruiting bodies of 25 species were screened in vitro for their antibacterial activities against three gram-positive bacteria (staphyloccocus aureus, bacillus subtilis, micrococcus flavus) and two gram-negative ba ...201323556343
complement component 3c3 and c3a receptor are required in chitin-dependent allergic sensitization to aspergillus fumigatus but dispensable in chitin-induced innate allergic inflammation.levels of the anaphylatoxin c3a are increased in patients with asthma compared with those in nonasthmatics and increase further still during asthma exacerbations. however, the role of c3a during sensitization to allergen is poorly understood. sensitization to fungal allergens, such as aspergillus fumigatus, is a strong risk factor for the development of asthma. exposure to chitin, a structural polysaccharide of the fungal cell wall, induces innate allergic inflammation and may promote sensitizat ...201323549917
culture condition-dependent metabolite profiling of aspergillus fumigatus with antifungal activity.three sections of aspergillus (five species, 21 strains) were classified according to culture medium-dependent and time-dependent secondary metabolite profile-based chemotaxonomy. secondary metabolites were analysed by liquid chromatography-electrospray ionisation tandem mass spectrometry (lc-esi-ms-ms) and multivariate statistical methods. from the aspergillus sections that were cultured on malt extract agar (mea) and czapek yeast extract agar (cya) for 7, 12, and 16 d, aspergillus sections fum ...201323537878
biological interactions between soil saprotrophic fungi and ascaris suum eggs.the in vitro effect of saprotrophic soil fungi on the embryonic development of ascaris suum was evaluated. the fungi tested were aspergillus fumigatus, aspergillus terreus, penicillium citrinum, penicillium expansum, fusarium oxysporum and trichothecium roseum, isolated from children's recreation areas in the city of lodz (poland). each species was co-cultured with a. suum egg suspension (6 × 10(3)eggs/ml) at 25 ± 2°c for 60 days. each day, 100 eggs were randomly collected and their developmenta ...201323534981
the fungal pathogen aspergillus fumigatus regulates growth, metabolism, and stress resistance in response to light.light is a pervasive environmental factor that regulates development, stress resistance, and even virulence in numerous fungal species. though much research has focused on signaling pathways in aspergillus fumigatus, an understanding of how this pathogen responds to light is lacking. in this report, we demonstrate that the fungus does indeed respond to both blue and red portions of the visible spectrum. included in the a. fumigatus light response is a reduction in conidial germination rates, inc ...201323532976
[functional role of protein kinase d1 in aspergillus fumigatus-induced activation of nuclear factor-κb signal pathway and transcription].to explore the functional role of protein kinase d1 (pkd1) in the activation of nuclear factor-κb (nf-κb) signal pathway and nf-κb transcription mediated by aspergillus fumigatus.201323529230
preemptive treatment with voriconazole in lung transplant recipients.invasive fungal infection (ifi) is associated with high mortality in lung transplant (ltx) recipients. data for voriconazole use in preemptive treatment remain scant.201323527908
transcriptome and biochemical analysis reveals that suppression of gpi-anchor synthesis leads to autophagy and possible necroptosis in aspergillus fumigatus.previously, it has been shown that gpi proteins are required for cell wall synthesis and organization in aspergillus fumigatus, a human opportunistic pathogen causing life-threatening invasive aspergillosis (ia) in immunocompromised patients. blocking gpi anchor synthesis leads to severe phenotypes such as cell wall defects, increased cell death, and attenuated virulence. however, the mechanism by which these phenotypes are induced is unclear. to gain insight into global effects of gpi anchoring ...201323527074
pharmacokinetic evaluation in mice of amorphous itraconazole-based dry powder formulations for inhalation with high bioavailability and extended lung retention.three itraconazole (itz) dry powders for inhalation (dpi) were prepared by spray-drying a mannitol solution in which the itz was in suspension (f1) or was in solution without (f2) or with phospholipid (pl) (f3). these powders were endotracheally insufflated in vivo at a single dose of 0.5mg/kg for pharmacokinetic profile (lung and plasma concentration) determination in icr cd-1 mice. itz was crystalline in f1 and assumed to be amorphous in the f2 and f3 formulations. f2 and f3 formulations allow ...201423523546
imaging living cells surface and quantifying its properties at high resolution using afm in qi™ mode.since the last 10 years, afm has become a powerful tool to study biological samples. however, the classical modes offered (imaging or tapping mode) often damage sample that are too soft or loosely immobilized. if imaging and mechanical properties are required, it requests long recording time as two different experiments must be conducted independently. in this study we compare the new qi™ mode against contact imaging mode and force volume mode, and we point out its benefit in the new challenges ...201323522742
assessment of aspergillus fumigatus pathogenicity in aerosol-challenged chickens (gallus gallus) belonging to two lineages.infection due to the mold aspergillus fumigatus remains a common and life-threatening infection in many animals, especially birds. animal models are still required to better understand the physiopathology of infection and evaluate diagnostic tools and treatment procedures. the aim of the present study was to assess the pathogenicity of a. fumigatus in two lineages of chicken (gallus gallus): spf white leghorn pa12 layers and conventional ja657 broilers. four-day-old birds were experimentally inf ...201323522612
importance of elastase production in development of invasive aspergillosis.to evaluate the relationship between elastase activity of different aspergillus fumigatus (a. fumigatus) isolates and their pathogenicity in mice.201223518019
intravenous antibiotics reduce the presence of aspergillus in adult cystic fibrosis sputum.pseudomonas aeruginosa and aspergillus fumigatus frequently co-colonise the airways of patients with cystic fibrosis (cf). this study aimed to assess the impact of short-term administration of intravenous antipseudomonal antibiotics during cf exacerbations on the presence of aspergillus.201323513028
monocyte- and macrophage-targeted nadph oxidase mediates antifungal host defense and regulation of acute inflammation in mice.chronic granulomatous disease, an inherited disorder of the nadph oxidase in which phagocytes are defective in the generation of superoxide anion and downstream reactive oxidant species, is characterized by severe bacterial and fungal infections and excessive inflammation. although nadph oxidase isoforms exist in several lineages, reactive oxidant generation is greatest in neutrophils, where nadph oxidase has been deemed vital for pathogen killing. in contrast, the function and importance of nad ...201323509361
sun proteins belong to a novel family of β-(1,3)-glucan-modifying enzymes involved in fungal morphogenesis.sun proteins are involved in yeast morphogenesis, but their function is unknown.201323508952
csp typing of chinese aspergillus fumigatus isolates: identification of additional csp types.cell surface protein (csp) typing is a typing strategy that employs comparative dna sequence analysis of the 12-mer tandem repeat region of the afua_3g08890 gene. the csp typing scheme and modified nomenclature was applied to a collection of 162 clinical aspergillus fumigatus isolates from china. a total of 16 csp variants were observed, including five that were newly reported, indicating that phylogeographic differences may exist between the chinese and the previously studied australian, europe ...201323506321
critical tests for determination of microbiological quality and biological activity in commercial vermicompost samples of different origins.the aim of the present paper was to show that differences in biological activity among commercially produced vermicompost samples can be found by using a relatively simple test system consisting of microorganism tests on six microbiological media and soilless seedling growth tests with four vegetable crop species. significant differences in biological properties among analyzed samples were evident both at the level of microbial load as well as plant growth-affecting activity. these differences w ...201323504062
novel terephthaloyl thiourea cross-linked chitosan hydrogels as antibacterial and antifungal agents.four novel terephthaloyl thiourea chitosan (ttu-chitosan) hydrogels were synthesized via a cross-linking reaction of chitosan with different concentrations of terephthaloyl diisothiocyanate. their structures were investigated by elemental analyses, ftir, sem and x-ray diffraction. the antimicrobial activities of the hydrogels against three species of bacteria (bacillis subtilis, staphylococcus aureus and escherichia coli) and three crop-threatening pathogenic fungi (aspergillus fumigatus, geotri ...201323500435
a magneto-nanosensor immunoassay for sensitive detection of aspergillus fumigatus allergen asp f 1.we report a magneto-nanosensor biochip for fungal detection. the chip is made of arrays of giant magnetoresistive (gmr) spin-valve sensors, and is able to detect protein biomarkers at low concentrations in solutions. as a demonstration, a standard curve for fungal pathogen asp f 1 was obtained by measuring signals from various concentrations of asp f 1 spiked in pbs solutions, indicating a detection limit of ~100 pg/ml. five positive and negative asp f 1 solution samples were discriminated corre ...201223494403
liver transplantation in cystic fibrosis: a report from baylor college of medicine and the texas children's hospital.cf affects one of 2000 caucasians, and approximately 25% are found to have cfld for which olt may be indicated. timing of transplantation, contraindications, and survival are still widely debated. we report the outcomes of olt for pediatric patients with cfld from the largest children's hospital in the united states. our records since september 1998 were analyzed for all patients undergoing olt for cfld. nine patients were then compared to similar patients in the unos/optn database (n = 155). su ...201323489441
the fumagillin biosynthetic gene cluster in aspergillus fumigatus encodes a cryptic terpene cyclase involved in the formation of β-trans-bergamotene.fumagillin 1 is a meroterpenoid from aspergillus fumigatus that is known for its anti-angiogenic activity by binding to human methionine aminopeptidase 2. the genetic and molecular basis for biosynthesis of 1 had been an enigma despite the availability of the a. fumigatus genome sequence. here, we report the identification and verification of the fma gene cluster, followed by characterization of the polyketide synthase and acyltransferase involved in biosynthesis of the dioic acid portion of 1. ...201323488861
[biological safety of the molluscicidal ingredient from aspergillus fumigatus sl-30 isolated from rhizosphere of phytolacca acinosa].to study biological safety of the molluscicidal ingredient (mi, a kind of diketopiperazines) in the exocellular broth of aspergillus fumigatus sl-30' which was isolated from the rhizosphere of phytolacca acinosa.201223484258
chloroquine modulates the fungal immune response in phagocytic cells from patients with chronic granulomatous disease.invasive aspergillosis is a major threat to patients with chronic granulomatous disease (cgd). fungal pathogenesis is the result of a diminished antifungal capacity and dysregulated inflammation. a deficient nadph-oxidase complex results in defective phagolysosomal alkalization. to investigate the contribution of defective ph regulation in phagocytes among patients with cgd during fungal pathogenesis, we evaluated the effect of the acidotropic, antimalarial drug chloroquine (cq) on the antifunga ...201323482646
identification and evaluation of novel acetolactate synthase inhibitors as antifungal agents.high-throughput phenotypic screening against the yeast saccharomyces cerevisiae revealed a series of triazolopyrimidine-sulfonamide compounds with broad-spectrum antifungal activity, no significant cytotoxicity, and low protein binding. to elucidate the target of this series, we have applied a chemogenomic profiling approach using the s. cerevisiae deletion collection. all compounds of the series yielded highly similar profiles that suggested acetolactate synthase (ilv2p, which catalyzes the fir ...201323478965
role of ficolin-a and lectin complement pathway in the innate defense against pathogenic aspergillus species.aspergillus species are saprophytic molds causing life-threatening invasive fungal infections in the immunocompromised host. innate immune recognition, in particular, the mechanisms of opsonization and complement activation, has been reported to be an integral part of the defense against fungi. we have shown that the complement component ficolin-a significantly binds to aspergillus conidia and hyphae in a concentration-dependent manner and was inhibited by n-acetylglucosamine and n-acetylgalacto ...201323478320
proteolytic cleavage of the long pentraxin ptx3 in the airways of cystic fibrosis patients.the prototypic long pentraxin ptx3, a soluble pattern recognition receptor, plays an important role in innate defense against selected pathogens by favoring their elimination and the initiation of protective responses. ptx3 has notably beneficial effects in mice infected with aspergillus fumigatus and pseudomonas aeruginosa. cystic fibrosis (cf), a severe inherited autosomal recessive disease, is characterized by recurrent lung infections, especially by these two pathogens. we thus hypothesized ...201323475792
synthesis, antimicrobial, antiquorum-sensing, antitumor and cytotoxic activities of new series of fused [1,3,4]thiadiazoles.new series of [1,3,4]thiadiazolo[3,2-a]pyrimidines, benzo[h][1,3,4]thiadiazolo[2,3-b]quinazolines, benzothiadiazolotriazocine, and imidazo[2,1-b][1,3,4]thiadiazoles have been synthesized and characterized by analytical and spectrometrical methods (ir, ms, (1)h and (13)c nmr). twenty of the synthesized compounds were screened for antibacterial activity against escherichia coli, staphylococcus aureus and bacillus cereus. they were found to be either moderately active, slightly active or inactive a ...201323474904
gliotoxinogenic aspergillus fumigatus in the dairy herd environment.the potential association between hygienic conditions in the environment of lactating cows and the presence of gliotoxinogenic aspergillus fumigatus strains was studied. milk samples (individual cow's milk [icm], bulk tank milk [btm]) from 44 dairy farms were sampled. in icm samples, eight different species of aspergillus were identified. a. flavus and a. fumigatus were predominant, with 37.8% and 26.1% relative densities, respectively. a. fumigatus strains were isolated from 61.4% of the btm sa ...201323467846
the tell-tale heart: aspergillus fumigatus endocarditis in an immunocompetent patient.aspergillus is a saprophytic, spore-forming fungus that is ubiquitous in our daily environment. inhalation of the airborne conidia leads to a variety of diseases, from asymptomatic colonization to disseminated disease. immunocompromised patients are usually viewed as the population most susceptible to aspergillosis because of their lack of host immune defenses. however, a healthy immune system does not preclude an individual from susceptibility to aspergillosis. our case illustrates an immunocom ...201323466974
efficacy of dna amplification in tissue biopsy samples to improve the detection of invasive fungal disease.the performance of a pan-fungal pcr-based technique was evaluated to assess the aetiology of invasive fungal diseases (ifds). a total of 89 formalin-fixed paraffin-embedded biopsy samples from 84 patients with proven ifd were studied. culture of tissue was performed in 68 (81%) patients. the sensitivities of the pcr-based technique and microbiological culture of tissues were 89% and 56%, respectively (p <0.01). according to pcr results, aspergillus species accounted for 67%, candida species for ...201323464751
azole resistance in aspergillus fumigatus from bronchoalveolar lavage fluid samples of patients with chronic diseases.triazole resistance in aspergillus fumigatus has been increasing. we explored the a. fumigatus azole resistance profiles in bronchoalveolar lavage (bal) fluid samples from danish patients examined for aspergillosis.201323463213
epidemiology of invasive fungal infections in the intensive care unit: results of a multicenter italian survey (aurora project).the aims of this study are to evaluate the epidemiology of invasive fungal infections (ifis) in patients admitted to an intensive care unit (icu) in southern italy and the in vitro antifungal susceptibility of isolates.201323463186
dectin-1 expression at early period of aspergillus fumigatus infection in rat's corneal epithelium.to investigate the expression of dendritic cell-associated c-type lectin-1(dectin-1) at the early period of aspergillus fumigatus infection in rat's corneal epithelium.201323447102
vitamin d regulation of ox40 ligand in immune responses to aspergillus fumigatus.ox40 ligand (ox40l) is a costimulatory molecule involved in th2 allergic responses. it has been shown that vitamin d deficiency is associated with increased ox40l expression in peripheral cd11c(+) cells and controls th2 responses to aspergillus fumigatus in vitro in cystic fibrosis (cf) patients with allergic bronchopulmonary aspergillosis (abpa). to investigate if vitamin d deficiency regulated ox40l and th2 responses in vivo, we examined the effect of nutritional vitamin d deficiency on costim ...201323439304
partial reconstruction of the ergot alkaloid pathway by heterologous gene expression in aspergillus nidulans.ergot alkaloids are pharmaceutically and agriculturally important secondary metabolites produced by several species of fungi. ergot alkaloid pathways vary among different fungal lineages, but the pathway intermediate chanoclavine-i is evolutionarily conserved among ergot alkaloid producers. at least four genes, dmaw, easf, ease, and easc, are necessary for pathway steps prior to chanoclavine-i; however, the sufficiency of these genes for chanoclavine-i synthesis has not been established. a fragm ...201323435153
receptor-mediated signaling in aspergillus fumigatus.aspergillus fumigatus is the most pathogenic species among the aspergilli, and the major fungal agent of human pulmonary infection. to prosper in diverse ecological niches, aspergilli have evolved numerous mechanisms for adaptive gene regulation, some of which are also crucial for mammalian infection. among the molecules which govern such responses, integral membrane receptors are thought to be the most amenable to therapeutic modulation. this is due to the localization of these molecular sensor ...201323430083
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