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low cost single-step purification of endoglucanase from aspergillus fumigatus abk-9.low cost agro-waste was used as adsorption support for single-step purification of endoglucanase from the culture filtrate of a. fumigatus abk-9. among various agro-waste substrates, 1% naoh pretreated rice bran was proved to be the best for adsorbing about 74.8 and 71.1% of endoglucanase at 4 degrees c and 10 degrees c respectively. langmuir type adsorption isotherm at 4 degrees c showed maximum adsorption of enzyme at ph 5.0, which was in the range of optimum ph of the enzyme. the rice bran co ...201324416930
[cloning, expression and characterization of beta-glucosidase from aspergillus fumigatus].exploring new beta-glucosidase genes is of great importance to industrialize beta-glucosidase. the genomes of aspergillus fumigatus contain a bgl gene, which encodes a 65 kda putative beta-glucosidase. the bgl gene was cloned into an expression plasmid and transformed to escherichia coli bl21 (de3). the bgl was expressed upon induction of isopropyl beta-d-1-thiogalactopyranoside (iptg). the recombinant protein was purified by gst-tag affinity chromatography. the purified recombinant bgl was char ...201324409688
identification and characterization of prokaryotic dipeptidyl-peptidase 5 from porphyromonas gingivalis.porphyromonas gingivalis, a gram-negative asaccharolytic anaerobe, is a major causative organism of chronic periodontitis. because the bacterium utilizes amino acids as energy and carbon sources and incorporates them mainly as dipeptides, a wide variety of dipeptide production processes mediated by dipeptidyl-peptidases (dpps) should be beneficial for the organism. in the present study, we identified the fourth p. gingivalis enzyme, dpp5. in a dpp4-7-11-disrupted p. gingivalis atcc 33277, a dpp7 ...201424398682
identification of a key lysine residue in heat shock protein 90 required for azole and echinocandin resistance in aspergillus fumigatus.heat shock protein 90 (hsp90) is an essential chaperone involved in the fungal stress response that can be harnessed as a novel antifungal target for the treatment of invasive aspergillosis. we previously showed that genetic repression of hsp90 reduced aspergillus fumigatus virulence and potentiated the effect of the echinocandin caspofungin. in this study, we sought to identify sites of posttranslational modifications (phosphorylation or acetylation) that are important for hsp90 function in a. ...201424395240
macrophage reporter cell assay for screening immunopharmacological activity of cell wall-active antifungals.antifungal exposure can elicit immunological effects that contribute to activity in vivo, but this activity is rarely screened in vitro in a fashion analogous to mic testing. we used raw 264.7 murine macrophages that express a secreted embryonic alkaline phosphatase (seap) gene induced by transcriptional activation of nf-κb and activator protein 1 (ap-1) to develop a screen for immunopharmacological activity of cell wall-active antifungal agents. isolates of candida albicans and aspergillus fumi ...201424395226
anethole induces apoptotic cell death accompanied by reactive oxygen species production and dna fragmentation in aspergillus fumigatus and saccharomyces cerevisiae.trans-anethole (anethole), a major component of anise oil, has a broad antimicrobial spectrum, and antimicrobial activity that is weaker than that of other antibiotics on the market. when combined with polygodial, nagilactone e, and n-dodecanol, anethole has been shown to possess significant synergistic antifungal activity against a budding yeast, saccharomyces cerevisiae, and a human opportunistic pathogenic yeast, candida albicans. however, the antifungal mechanism of anethole has not been com ...201424393541
ecology drives the distribution of specialized tyrosine metabolism modules in fungi.gene clusters encoding accessory or environmentally specialized metabolic pathways likely play a significant role in the evolution of fungal genomes. two such gene clusters encoding enzymes associated with the tyrosine metabolism pathway (kegg #00350) have been identified in the filamentous fungus aspergillus fumigatus. the l-tyrosine degradation (td) gene cluster encodes a functional module that facilitates breakdown of the phenolic amino acid, l-tyrosine through a homogentisate intermediate, b ...201424391152
de novo design of non-coordinating indolones as potential inhibitors for lanosterol 14-α-demethylase (cyp51).the development of antifungal drugs that inhibit lanosterol 14-α-demethylase (cyp51) via non-covalent ligand interactions is a strategy that is gaining importance. a series of novel tetraindol-4-one derivatives with 1- and 2-(2,4-substituted phenyl) side chains were designed and synthesized based on the structure of cyp51 and fluconazole. the antifungal activities of these derivatives against eight human pathogenic filamentous fungi and yeast strains were evaluated in vitro by measuring the mini ...201424390489
incidence of non-candidal fungal infections in severe burn injury: an australian perspective.infection remains the primary cause of morbidity and mortality in the burns patient population. while candidal infection in burns patients is well described, there is dearth of information regarding non-candidal fungal infections in this setting.201424380706
nanodisk containing super aggregated amphotericin b: a high therapeutic index antifungal formulation with enhanced potency.nanodisk-amphotericin b (nd-amb) is a protein-phospholipid bioparticle containing a "super aggregate" form of antifungal amb. while lipid-based formulations of amb, including liposomal amb (l-amb), are safer than the deoxycholate (doc) solubilized form (doc-amb), the potency of lipid-based formulations is attenuated. we have developed an amb-based therapy that is both well tolerated and fully efficacious.201324379661
eosinophil deficiency compromises lung defense against aspergillus fumigatus.exposure to the mold aspergillus fumigatus may result in allergic bronchopulmonary aspergillosis, chronic necrotizing pulmonary aspergillosis, or invasive aspergillosis (ia), depending on the host's immune status. neutrophil deficiency is the predominant risk factor for the development of ia, the most life-threatening condition associated with a. fumigatus exposure. here we demonstrate that in addition to neutrophils, eosinophils are an important contributor to the clearance of a. fumigatus from ...201424379296
susceptibility testing in aspergillus species complex.methods for susceptibility testing of aspergillus are developed and validated by the european committee on antibiotic susceptibility testing subcommittee on antifungal susceptibility testing. breakpoints for phenotypic antimicrobial susceptibility testing have been determined by breakpoint committees and as part of regulatory processes for the approval of new drugs. dosages, pharmacokinetics, resistance mechanisms, mic distributions, pharmacodynamics and epidemiological cut-off values are used i ...201424372722
enhancement of biodegradation of palm oil mill effluents by local isolated microorganisms.this study was designed to investigate the microorganisms associated with palm oil mill effluent (pome) in johor bahru state, malaysia. biodegradation of palm oil mill effluents (pome) was conducted to measure the discarded pome based on physicochemical quality. the bacteria that were isolated are micrococcus species, bacillus species, pseudomonas species, and staphylococcus aureus, while the fungi that were isolated are aspergillus niger, aspergillus fumigatus, candida species, fusarium species ...201427433516
allergic bronchopulmonary mycosis due to co-infection with aspergillus fumigatus and schizophyllum commune.a 61-year-old female presented with eosinophilic pneumonia accompanied by bronchial asthma. she was finally diagnosed with allergic bronchopulmonary mycosis (abpm) due to co-infection with aspergillus fumigatus and schizophyllum commune detected by genetic analysis of the plug and from cultures.201426839766
direct transbronchial administration of liposomal amphotericin b into a pulmonary aspergilloma.pulmonary aspergillomas usually occur in pre-existing lung cavities exhibiting local immunodeficiency. as pulmonary aspergillomas only partially touch the walls of the cavities containing them, they rarely come into contact with the bloodstream, which makes it difficult for antifungal agents to reach them. although surgical treatment is the optimal strategy for curing the condition, most patients also have pulmonary complications such as tuberculosis and pulmonary fibrosis, which makes this stra ...201426029520
bioaerosols from a food waste composting plant affect human airway epithelial cell remodeling genes.the composting procedure in food waste plants generates airborne bioaerosols that have the potential to damage human airway epithelial cells. persistent inflammation and repair responses induce airway remodeling and damage to the respiratory system. this study elucidated the expression changes of airway remodeling genes in human lung mucoepidermoid nci-h292 cells exposed to bioaerosols from a composting plant. different types of microorganisms were detectable in the composting plant, using the a ...201324368426
the three aspergillus fumigatus cfem-domain gpi-anchored proteins (cfma-c) affect cell-wall stability but do not play a role in fungal virulence.fungal cell-wall proteins containing the conserved fungal cfem domain have been implicated in host-pathogen interactions and virulence. to determine the role of these proteins in the mold pathogen aspergillus fumigatus, we deleted the entire family of three cfem-containing genes (cfma-c), singly and in all combinations. we found an additive increase in the susceptibility of the single, double and triple δcfm mutants towards the chitin/β-glucan-microfibril destabilizing compounds congo red (cr) a ...201424361821
reactive oxygen species-inducing antifungal agents and their activity against fungal biofilms.invasive fungal infections are associated with very high mortality rates ranging from 20-90% for opportunistic fungal pathogens such as candida albicans, cryptococcus neoformans and aspergillus fumigatus. fungal resistance to antimycotic treatment can be genotypic (due to resistant strains) as well as phenotypic (due to more resistant fungal lifestyles, such as biofilms). with regard to the latter, biofilms are considered to be critical in the development of invasive fungal infections. however, ...201424358949
fumigaclavine c from a marine-derived fungus aspergillus fumigatus induces apoptosis in mcf-7 breast cancer cells.recently, much attention has been given to discovering natural compounds as potent anti-cancer candidates. in the present study, the anti-cancer effects of fumigaclavine c, isolated from a marine-derived fungus, aspergillus fumigatus, was evaluated in vitro. in order to investigate the impact of fumigaclavine c on inhibition of proliferation and induction of apoptosis in breast cancer, mcf-7 cells were treated with various concentrations of fumigaclavine c, and fumigaclavine c showed significant ...201324351905
aspergillus fumigatus--what makes the species a ubiquitous human fungal pathogen? 201324348239
crystal structures of the fungal pathogen aspergillus fumigatus protein farnesyltransferase complexed with substrates and inhibitors reveal features for antifungal drug design.species of the fungal genus aspergillus are significant human and agricultural pathogens that are often refractory to existing antifungal treatments. protein farnesyltransferase (ftase), a critical enzyme in eukaryotes, is an attractive potential target for antifungal drug discovery. we report high-resolution structures of a. fumigatus ftase (afftase) in complex with substrates and inhibitors. comparison of structures with farnesyldiphosphate (fpp) bound in the absence or presence of peptide sub ...201424347326
a new diphenyl ether from the endophytic fungus verticillium sp. isolated from rehmannia glutinosa.to investigate the chemical constituents of the endophytic fungus verticillium sp. isolated from rehmannia glutinosa.201324345509
in vitro analyses of mild heat stress in combination with antifungal agents against aspergillus fumigatus biofilm.aspergillus fumigatus biofilms still present a challenge for effective treatment in clinical settings. while mild heat stress has been introduced as a treatment for infectious diseases, the effectiveness of mild heat stress on a. fumigatus biofilm formation and antifungal susceptibility is still unknown. in the present study, confocal laser scanning microscopy (clsm) was used to image and quantify aspergillus fumigatus biofilm formation under three different regimens of continuous mild heat stre ...201424342649
aspergillus sensitization or carriage in cystic fibrosis patients.aspergillus fumigatus (af) sensitization and persistent carriage are deleterious to lung function, but no consensus has been reached defining these medical entities. this work aimed to identify possible predictive factors for patients who become sensitized to af, compared with a control group of non-sensitized af carriers.201424336095
synthesis and evaluation of novel azoles as potent antifungal agents.using a rational approach to the design of antifungal agents, a series of azole agents with 1,3,4-oxadiazole side chains were designed and synthesized. the results of preliminary in vitro antifungal tests with eight human pathogenic compounds showed that all of the title compounds exhibited excellent activities against all of the tested fungi except aspergillus fumigatus. compounds 11e and 11f were found to be the most effective, with a minimum inhibitory concentration of 0.0039μg/ml, followed b ...201424332489
role of prostaglandin d2 /crth2 pathway on asthma exacerbation induced by aspergillus fumigatus.aspergillus fumigatus is often associated in asthmatic patients with the exacerbation of asthma symptoms. the pathomechanism of this phenomenon has not been fully understood. here, we evaluated the immunological mechanisms and the role of the prostaglandin d2 / chemoattractant receptor-homologous molecule expressed on th2 cells (crth2) pathway in the development of aspergillus-associated asthma exacerbation. we studied the effects of a. fumigatus on airway inflammation and bronchial hyper-respon ...201424329550
hypothermic endpoint for an intranasal invasive pulmonary aspergillosis mouse model.immunocompromised mice were infected intranasally with aspergillus fumigatus as part of a vaccine efficacy study. although body temperature was measured throughout the study, a formal evaluation of its usefulness as an endpoint criterion was not performed. we retrospectively evaluated survival data and temperature records to determine whether body temperature can be used as an objective predictor of death and included in the humane endpoint criteria for this mouse model. cf1 mice were immunosupp ...201324326222
an important finding of systemic aspergillosis: skin involvement and amphotericin b resistance in an adolescent.invasive aspergillosis is a life-threatening infectious complication in immunocompromised patients, especially with malignancy, and in some cases, it causes extensive tissue destruction and subsequent systemic illness, leading to multiorgan failure and death. skin involvement and amphotericin b resistance are very rare findings of aspergillosis. herein, we report the case of a primary hemophagocytic syndrome patient who developed subcutaneous nodules in the 3(rd) month of bone marrow transplanta ...201624326152
crystallization and preliminary x-ray diffraction studies of the (r)-selective amine transaminase from aspergillus fumigatus.the (r)-selective amine transaminase from aspergillus fumigatus was expressed in escherichia coli and purified to homogeneity. bright yellow crystals appeared while storing the concentrated solution in the refrigerator and belonged to space group c222(1). x-ray diffraction data were collected to 1.27 å resolution, as well as an anomalous data set to 1.84 å resolution that was suitable for s-sad phasing.201324316843
crystal structure and biochemical characterization of a manganese superoxide dismutase from chaetomium thermophilum.a manganese superoxide dismutase from the thermophilic fungus chaetomium thermophilum (ctmnsod) was expressed in pichia pastoris and purified to homogeneity. its optimal temperature was 60°c with approximately 75% of its activity retained after incubation at 70°c for 60min. recombinant yeast cells carrying c. thermophilum mnsod gene exhibited higher stress resistance to salt and oxidative stress-inducing agents than control yeast cells. in an effort to provide structural insights, ctmnsod was cr ...201424316252
evaluation of pulmonary infections in solid organ transplant patients: 12 years of experience.recipients of solid organ transplants (sots) are at higher risk to develop pulmonary infections (pis) owing to their immunocompromised state. flexible bronchoscopy (fb) is frequently performed to diagnose nature of these infections. the aim of 12-year review was to evaluate the demographic characteristics of sot recipients with pis and to study diagnostic utility of fb in this group of patients.201324314931
treatment options in severe fungal asthma and allergic bronchopulmonary aspergillosis.severe asthma with fungal sensitisation and allergic bronchopulmonary aspergillosis encompass two closely related subgroups of patients with severe allergic asthma. pulmonary disease is due to pronounced host inflammatory responses to noninvasive subclinical endobronchial infection with filamentous fungi, usually aspergillus fumigatus. these patients usually do not achieve satisfactory disease control with conventional treatment of severe asthma, i.e. high-dose inhaled corticosteroids and long-a ...201424311776
antigen-specific expansion of human regulatory t cells as a major tolerance mechanism against mucosal fungi.foxp3(+) regulatory t cells (treg) have a central role for keeping the balance between pro- and anti-inflammatory immune responses against chronically encountered antigens at mucosal sites. however, their antigen specificity especially in humans is largely unknown. here we used a sensitive enrichment technology for antigen-reactive t cells to directly compare the conventional vs. regulatory cd4(+) t-cell response directed against two ubiquitous mucosal fungi, aspergillus fumigatus and candida al ...201424301658
activated mouse eosinophils protect against lethal respiratory virus infection.eosinophils are recruited to the airways as a prominent feature of the asthmatic inflammatory response where they are broadly perceived as promoting pathophysiology. respiratory virus infections exacerbate established asthma; however, the role of eosinophils and the nature of their interactions with respiratory viruses remain uncertain. to explore these questions, we established acute infection with the rodent pneumovirus, pneumonia virus of mice (pvm), in 3 distinct mouse models of th2 cytokine ...201424297871
kinetic and structural evaluation of selected active site mutants of the aspergillus fumigatus kdnase (sialidase).aspergillus fumigatus is an airborne fungal pathogen. we previously cloned and characterized an exo-sialidase from a. fumigatus and showed that it preferred 2-keto-3-deoxynononic acid (kdn) as a substrate to n-acetylneuraminic acid (neu5ac). the purpose of this study was to investigate the structure-function relationships of critical catalytic site residues. site-directed mutagenesis was used to create three mutant recombinant enzymes: the catalytic nucleophile (y358h), the general acid/base cat ...201324295366
enhanced production of fumigaclavine c in liquid culture of aspergillus fumigatus under a two-stage process.fumigaclavine c (fc) produced by aspergillus fumigatus is a conidiation associated ergot alkaloid with strong anti-inflammatory activity. however, its wide application has been severely limited by low fc production from submerged culture. in this work, a novel two-stage culture process by combining shake culture with static culture was proposed to enhance the production of fc. after the process optimization, the fc production reached 62.7 mg/l, which was significantly higher than ever report. fo ...201424291794
isolation and structural elucidation of novel cholestane glycosides and spirostane saponins from polygonatum odoratum.much attention has been paid to cholestane-type steroidal glycosides because of their importance from the perspectives of both chemical diversity and significant biological activities. a phytochemical investigation of the rhizomes of polygonatum odoratum (liliaceae) resulted in the isolation of three novel cholestane-type steroidal glycosides (1-3) with unique δ(14,16)-unsaturated d-ring structures as well as two novel spirostane-type steroidal saponins (4 and 5) and three known steroidal glycos ...201424291419
effectiveness of voriconazole in the treatment of aspergillus fumigatus-associated asthma (evita3 study).ige sensitization to aspergillus fumigatus and a positive sputum fungal culture result are common in patients with refractory asthma. it is not clear whether these patients would benefit from antifungal treatment.201424290286
induction of innate immunity by aspergillus fumigatus cell wall polysaccharides is enhanced by the composite presentation of chitin and beta-glucan.chitin and β-glucan are conserved throughout evolution in the fungal cell wall and are the most common polysaccharides in fungal species. together, these two polysaccharides form a structural scaffold that is essential for the survival of the fungus. in the present study, we demonstrated that aspergillus fumigatus alkali-insoluble cell wall fragments (aif), composed of chitin linked covalently to β-glucan, induced enhanced immune responses when compared with individual cell wall polysaccharides. ...201424286790
an in vitro study of the antimicrobial effects of indigo naturalis prepared from strobilanthes formosanus moore.indigo naturalis is effective in treating nail psoriasis coexisting with microorganism infections. this study examines the antimicrobial effects of indigo naturalis prepared from strobilanthes formosanus moore. eight bacterial and seven fungal strains were assayed using the agar diffusion method to examine the effects of indigo naturalis and its bioactive compounds. the bioactive compounds of indigo naturalis were purified sequentially using gfc, tlc, and hplc. their structures were identified u ...201324284490
why is mucormycosis more difficult to cure than more common mycoses?although considered to be a rare infection, mucormycosis (zygomycosis) has emerged as the second most common invasive mould infection. despite the advent of newer antifungal agents, mortality rate of mucormycosis remains exceedingly high. successful management of mucormycosis requires early diagnosis, reversal of underlying predisposing risk factors, surgical debridement and prompt administration of active antifungal agents. however, mucormycosis is not always amenable to cure. there are challen ...201424279587
a novel class of fungal lipoxygenases.lipoxygenases (loxs) are well-studied enzymes in plants and mammals. however, fungal loxs are less studied. in this study, we have compared fungal lox protein sequences to all known characterized loxs. for this, a script was written using shell commands to extract sequences from the ncbi database and to align the sequences obtained using multiple sequence comparison by log-expectation. we constructed a phylogenetic tree with the use of quicktree to visualize the relation of fungal loxs towards o ...201424276623
a prominent role for the il1 pathway and il15 in susceptibility to chronic cavitary pulmonary aspergillosis.chronic cavitary pulmonary aspergillosis (ccpa) is a progressive lung condition with a 10-30% annual mortality. although overtly immunocompetent, some immunogenetic defect in patients is likely. to investigate a possible immunogenetic defect in ccpa, we analysed biologically plausible candidate genes in 112 ccpa patients and 279 healthy controls in a genetic association study of genes involved in the post-recognition immune response to aspergillus fumigatus. we also compared gene expression in m ...201424274595
feline aspergillosis.feline aspergillosis includes sinonasal aspergillosis (sna), sino-orbital aspergillosis (soa), other focal invasive forms, and disseminated disease. soa is an invasive mycosis that is being increasingly recognized, and is most commonly caused by a recently discovered pathogen aspergillus felis. sna can be invasive or noninvasive and is most commonly caused by aspergillus fumigatus and aspergillus niger. molecular methods are required to correctly identify the fungi that cause sna and soa. sna ha ...201424268333
a case of acute cerebral aspergillosis complicating influenza a/h1n1pdm 2009.invasive aspergillosis is a rare complication in patients with influenza infection. several cases of invasive pulmonary aspergillosis accompanying influenza infections were reported during the influenza a/h1n1pdm 2009. we encountered a case of acute cerebral aspergillosis in a patient with influenza a/h1n1pdm 2009 infection. a 24-year-old man with uncontrolled diabetes was diagnosed with influenza a/h1n1pdm 2009 infection. initial evaluation indicated methicillin-sensitive staphylococcus aureus ...201324265971
an immunomodulatory activity of micafungin in preclinical aspergillosis.micafungin inhibits 1,3-β-d-glucan synthase and interferes with fungal cell wall synthesis. clinically, micafungin has been shown to be efficacious for the treatment of invasive fungal infections. however, little is known about the immunomodulatory activity of micafungin in these infections.201424265229
characterization of fungal keratitis in alpacas: 11 cases (2003-2012).to describe clinical, microbiological, in vivo confocal microscopic, and histopathologic features of fungal keratitis in alpacas and to estimate prevalence of the disease in a population of alpacas from the northeastern united states.201324261813
overlapping and distinct roles of aspergillus fumigatus udp-glucose 4-epimerases in galactose metabolism and the synthesis of galactose-containing cell wall polysaccharides.the cell wall of aspergillus fumigatus contains two galactose-containing polysaccharides, galactomannan and galactosaminogalactan, whose biosynthetic pathways are not well understood. the a. fumigatus genome contains three genes encoding putative udp-glucose 4-epimerases, uge3, uge4, and uge5. we undertook this study to elucidate the function of these epimerases. we found that uge4 is minimally expressed and is not required for the synthesis of galactose-containing exopolysaccharides or galactos ...201424257745
highlights in pathogenic fungal biofilms.a wide variety of fungi have demonstrated the ability to colonize surfaces and form biofilms. most studies on fungal biofilms have focused on candida albicans and more recently, several authors have reported the involvement of other genera of yeasts and candida species, as well as of filamentous fungi in the formation of biofilms, including: cryptococcus neoformans, cryptococcus gattii, rhodotorula species, aspergillus fumigatus, malassezia pachydermatis, histoplasma capsulatum, paracoccidioides ...201424252828
the zrfc alkaline zinc transporter is required for aspergillus fumigatus virulence and its growth in the presence of the zn/mn-chelating protein calprotectin.aspergillus fumigatus can invade the lungs of immunocompromised individuals causing a life-threatening disease called invasive pulmonary aspergillosis (ipa). to grow in the lungs, a. fumigatus obtains from the host all nutrients, including zinc. in living tissues, however, most zinc is tightly bound to zinc-binding proteins. moreover, during infection the bioavailability of zinc can be further decreased by calprotectin, an antimicrobial zn/mn-chelating protein that is released by neutrophils in ...201424245710
deletion of the α-(1,3)-glucan synthase genes induces a restructuring of the conidial cell wall responsible for the avirulence of aspergillus fumigatus.α-(1,3)-glucan is a major component of the cell wall of aspergillus fumigatus, an opportunistic human fungal pathogen. there are three genes (ags1, ags2 and ags3) controlling the biosynthesis of α-(1,3)-glucan in this fungal species. deletion of all the three ags genes resulted in a triple mutant that was devoid of α-(1,3)-glucan in its cell wall; however, its growth and germination was identical to that of the parental strain in vitro. in the experimental murine aspergillosis model, this mutant ...201324244155
deletion of the putative stretch-activated ion channel mid1 is hypervirulent in aspergillus fumigatus.calcium ion is a universal and physiologically important molecule affecting almost every cellular function, while mid1 (mating induced death) is a stretch-activated ion channel localized in the plasma membrane, which can replenish the fungus with extracellular calcium. aspergillus fumigatus is one of the most important fungal pathogens but little is known about its calcium channels in the plasma membrane. in this study, a homolog of saccharomyces cerevisiae mid1 was identified in a. fumigatus an ...201424239700
supercluster takes a walk on the wild side.in a recent proc. natl. acad. sci. usa paper by wiemann et al., a gene supercluster for secondary metabolite production in aspergillus fumigatus is genetically dissected. the analysis demonstrates that gene regulation takes place at different layers and that genes belonging to specific clusters are intertwined.201324239205
synthesis and characterization of some novel antimicrobial thiosemicarbazone o-carboxymethyl chitosan derivatives.three novel thiosemicarbazone o-carboxymethyl chitosan derivatives were obtained via a condensation reaction of thiosemicarbazide o-carboxymethyl chitosan with o-hydroxybenzaldehyde, p-methoxybenzaldehyde, and p- chlorobenzaldehyde respectively. their structures were characterized by elemental analysis, ftir, (13)c nmr and x-ray diffraction. the antimicrobial behaviors of the prepared derivatives against three types of bacteria staphylococcus aureus (s. aureus, rcmba 2004), bacillus subtilis (b. ...201424211430
prostatic and renal aspergillosis due to aspergillus fumigatus in a patient receiving alemtuzumab for chronic lymphocytic leukaemia.treatment of chronic lymphocytic leukaemia (cll) is rapidly evolving, with emerging new drugs. alemtuzumab is a monoclonal antibody recognizing cd52 antigen approved in the treatment of relapsing-refractory cll. a frequent side effect is the immunosuppression and patients treated with alemtuzumab risk to develop fungal infections such as aspergillosis.201324210582
snapafu: a novel single nucleotide polymorphism multiplex assay for aspergillus fumigatus direct detection, identification and genotyping in clinical specimens.early diagnosis of invasive aspergillosis is essential for positive patient outcome. likewise genotyping of fungal isolates is desirable for outbreak control in clinical setting. we designed a molecular assay that combines detection, identification, and genotyping of aspergillus fumigatus in a single reaction.201324204585
are we there yet? recent progress in the molecular diagnosis and novel antifungal targeting of aspergillus fumigatus and invasive aspergillosis. 201324204250
emergence of azole-resistant aspergillus fumigatus strains due to agricultural azole use creates an increasing threat to human health. 201324204249
allergic bronchopulmonary aspergillosis in asthma: epidemiological, clinical and therapeutic issues.allergic bronchopulmonary aspergillosis (abpa) is a complex pulmonary disorder caused by immunologic reactions to antigens released by aspergillus fumigatus, a ubiquitous fungi colonizing the tracheobronchial tree of asthmatic patients. the clinical presentation is usually poorly controlled asthma, recurrent pulmonary opacities and bronchiectasis. the prevalence of abpa in asthma clinics may be as high as 13% with a global burden of almost 5 million patients. a. fumigatus-specific ige level is t ...201324199804
angiogenesis at the mold-host interface: a potential key to understanding and treating invasive aspergillosis.invasive aspergillosis (ia) in neutropenic patients is characterized by angioinvasion, intravascular thrombosis and tissue infarction, features that lead to sequestration of infected tissue and impaired fungal clearance. recent research has shown that host angiogenesis, the homeostatic compensatory response to tissue hypoxia, is downregulated by aspergillus fumigatus secondary metabolites. a. fumigatus metabolites inhibit multiple key angiogenic mediators, notably basic fgf, vegf and their respe ...201324199803
expression and activity of catalases is differentially affected by gpaa (ga) and flba (regulator of g protein signaling) in aspergillus fumigatus.vegetative growth signaling of the opportunistic human pathogenic fungus aspergillus fumigatus is mediated by gpaa (gα). flba is a regulator of g protein signaling, which attenuates gpaa-mediated growth signaling in this fungus. the flba deletion (δflba) and the constitutively active gpaa (gpaa(q204l)) mutants exhibit enhanced proliferation, precocious autolysis, and reduced asexual sporulation. in this study, we demonstrate that both mutants also show enhanced tolerance against h2o2 and their r ...201324198669
recurrent pulmonary aspergillosis and mycobacterial infection in an unsplenectomized patient with type 1 gaucher disease.the clinical presentation of gaucher disease (gd), an inherited lysosomal storage disorder caused by the deficient activity of the lysosomal enzyme glucocerebrosidase, is highly variable, and three clinical types are distinguished based upon the presence of neurologic symptoms. thrombocytopenia, anemia, hepatosplenomegaly, and bone manifestations are the most typical signs of gd type 1 (gd1).201424195576
the aspergillus genome database: multispecies curation and incorporation of rna-seq data to improve structural gene annotations.the aspergillus genome database (aspgd; http://www.aspgd.org) is a freely available web-based resource that was designed for aspergillus researchers and is also a valuable source of information for the entire fungal research community. in addition to being a repository and central point of access to genome, transcriptome and polymorphism data, aspgd hosts a comprehensive comparative genomics toolbox that facilitates the exploration of precomputed orthologs among the 20 currently available asperg ...201424194595
the fungal upr: a regulatory hub for virulence traits in the mold pathogen aspergillus fumigatus.aspergillus fumigatus is an opportunistic pathogen that is responsible for a life-threatening fungal infection known as invasive aspergillosis. current therapies for the treatment of this disease continue to be associated with a poor outcome, so there is a need for more information about aspects of the fungus-host interaction that could offer novel targets for drug intervention. one attractive possibility is the unfolded protein response (upr), an intracellular signaling network that helps the f ...201424189125
potential allelopathic indole diketopiperazines produced by the plant endophytic aspergillus fumigatus using the one strain-many compounds method.on the basis of the osmac (one strain-many compounds) strategy, 14 indole diketopiperazine (dkp) alkaloids, including spirotryprostatins (1-3), tryprostatins (4-6), and cyclotryprostatins (7-14), were isolated from the endophyte aspergillus fumigatus associated with melia azedarach l. their structures were identified by nuclear magnetic resonance and electrospray ionization mass spectrometry data. all the indole dkps were evaluated for plant growth regulation using the lettuce (lactuca sativa) s ...201324188331
double-stranded rna mycovirus infection of aspergillus fumigatus is not dependent on the genetic make-up of the host.aspergillus fumigatus is a fungus that causes opportunistic infections in immunocompromised patients, with high morbidity and mortality. in its turn, a. fumigatus can become infected with mycoviruses. most mycoviruses have a dsrna genome and can cause fungal hypovirulence. for that reason, mycoviruses could theoretically be used as therapeutic tools to combat fungal infections. we determined if a certain genetic make-up of a. fumigatus was associated with the presence of mycoviruses in 86 clinic ...201324167572
antimicrobial activity and cytotoxicity of the ethanol extract, fractions and eight compounds isolated from eriosema robustum (fabaceae).the aim of this study was to evaluate the antimicrobial activity and the cytotoxicity of the ethanol crude extract, fractions and isolated compounds from the twigs of eriosema robustum, a plant used for the treatment of coughs and skin diseases.201324165199
human natural killer cells acting as phagocytes against candida albicans and mounting an inflammatory response that modulates neutrophil antifungal activity.natural killer (nk) cells are innate lymphocytes with potent cytotoxic activity. whereas activity of nk cells has been demonstrated against the fungal pathogens aspergillus fumigatus and cryptococcus neoformans, little was known about their interaction with candida albicans.201424163416
production and partial characterization of serine and metallo peptidases secreted by aspergillus fumigatus fresenius in submerged and solid state fermentation.enzyme production varies in different fermentation systems. enzyme expression in different fermentation systems yields important information for improving our understanding of enzymatic production induction. comparative studies between solid-state fermentation (ssf) using agro-industrial waste wheat bran and submerged fermentation (smf) using synthetic media were carried out to determinate the best parameters for peptidase production by the fungus aspergillus fumigatus fresen. variables tested i ...201324159310
monitoring environmental aspergillus spp. contamination and meteorological factors in a haematological unit.the opportunistic pathogens belonging to the aspergillus genus are present in almost all seasons of the year, and their concentration is related to meteorological conditions. the high density of aspergillus spp. conidia in a haematological hospital ward may be a significant risk factor for developing invasive fungal diseases in immunocompromised patients. aim of the present study was to evaluate the variability of airborne aspergillus spp. conidia contamination in a haematological unit (hu) with ...201324158616
aspergillus fumigatus invasion increases with progressive airway ischemia.despite the prevalence of aspergillus-related disease in immune suppressed lung transplant patients, little is known of the host-pathogen interaction. because of the mould's angiotropic nature and because of its capacity to thrive in hypoxic conditions, we hypothesized that the degree of aspergillus invasion would increase with progressive rejection-mediated ischemia of the allograft. to study this relationship, we utilized a novel orthotopic tracheal transplant model of aspergillus infection, i ...201324155924
role of carbonic anhydrases in pathogenic micro-organisms: a focus on aspergillus fumigatus.aspergillus fumigatus is a ubiquitous saprophytic fungus responsible for organic material decomposition, and plays an important role in recycling environmental carbon and nitrogen. besides its important role in the environment, this fungus has been reported as one of the most important fungal pathogens in immunocompromised patients. due to changes in co2 concentration that some pathogens face during the infection process, studies have been undertaken to understand the pathogenic roles of carboni ...201424149624
[the treatment of aspergillus empyema using open thoraco-myoplasty with the preservation of lung function -- case report].invasive aspergillosis is a life threatening complication in immune-compromised patients causing lung tissue destruction. aspergillus empyema requires aggressive multimodality treatment.201324144821
in-silico characterization of β-(1, 3)-endoglucanase (engl1) from aspergillus fumigatus by homology modeling and docking studies.during the past few years a significant rise in aspergillosis caused by filamentous fungus aspergillus fumigatus has been recorded particularly in immunocompromised patients. at present, there are limited numbers of antifungal agents to combat these infections and the situation has become more complex due to emergence of antifungal resistance and side-effects of antifungal drugs. these situations have increased the demand for novel drug targets. recent studies have revealed that the β-1,3-endogl ...201324143049
laccase production optimization by response surface methodology with aspergillus fumigatus af1 in unique inexpensive medium and decolorization of different dyes with the crude enzyme or fungal pellets.in the present study, alkaline pretreatment was applied for the enhanced laccase production from rice straw. various process parameters including sodium hydroxide concentration, ph and fermentation temperature were optimized via response surface methodology (rsm) with a box-behnken design (bbd). through regression analysis, it was found that laccase activity was well fitted by a quadratic polynomial equation (r(2)=0.998, adj r(2)=0.995), and the fermentation temperature was the most significant ...201324140539
biosorption characteristics of aspergillus fumigatus for the decolorization of triphenylmethane dye acid violet 49.this study focuses on the possible use of aspergillus fumigatus to remove acid violet 49 dye (av49) from aqueous solution. in batch biosorption experiments, the highest biosorption efficiency was achieved at ph 3.0, with biosorbent dosage of 3.0 gl(-1) within about 30 min at 40 °c. the langmuir and freundlich models were able to describe the biosorption equilibrium of av49 onto fungal biomass with maximum dye uptake capacity 136.98 mg g(-1). biosorption followed a pseudo-second-order kinetic mod ...201424136473
secretome diversity and quantitative analysis of cellulolytic aspergillus fumigatus z5 in the presence of different carbon sources.aspergillus fumigatus z5 has a strong ability to decompose lignocellulose biomass, and its extracellular protein secretion has been reported in earlier studies employing traditional techniques. however, a comprehensive analysis of its secretion in the presence of different carbon sources is still lacking. the goal of this work was to identify, quantify and compare the secretome of a. fumigatus z5 in the presence of different carbon sources to understand in more details the mechanisms of lignocel ...201324131596
azole resistance in aspergillus fumigatus: a growing public health concern.reports from the end of the 2000s forced the medical community to take azole resistance in aspergillus fumigatus into account. not only patients with chronic aspergillus disease, who develop resistance during long-term azole treatment, but also azole-naive patients are at risk, owing to the presence of resistant strains in the environment. the purpose of this review is to overview the latest findings concerning the origin, evolution, and implications of azole resistance in a. fumigatus.201324126719
aspergillus collagen-like genes (acl): identification, sequence polymorphism, and assessment for pcr-based pathogen detection.the genus aspergillus is a burden to public health due to its ubiquitous presence in the environment, its production of allergens, and wide demographic susceptibility among cystic fibrosis, asthmatic, and immunosuppressed patients. current methods of detection of aspergillus colonization and infection rely on lengthy morphological characterization or nonstandardized serological assays that are restricted to identifying a fungal etiology. collagen-like genes have been shown to exhibit species-spe ...201324123732
assessment of selection and resistance risk for demethylation inhibitor fungicides in aspergillus fumigatus in agriculture and medicine: a critical review.an increasing number of publications have claimed that demethylation inhibitor (dmi) fungicides are confronted with resistance development in the fungus aspergillus fumigatus and that the origin of resistant isolates may also be outside the medical area. for resistance risk assessment and sourcing the origin of dmi resistance, the primary exposure events ofa. fumigatus with dmi treatments have been analysed case by case, resulting in the pathogen exposure risk (per).201424123539
laccases involved in 1,8-dihydroxynaphthalene melanin biosynthesis in aspergillus fumigatus are regulated by developmental factors and copper homeostasis.aspergillus fumigatus produces heavily melanized infectious conidia. the conidial melanin is associated with fungal virulence and resistance to various environmental stresses. this 1,8-dihydroxynaphthalene (dhn) melanin is synthesized by enzymes encoded in a gene cluster in a. fumigatus, including two laccases, abr1 and abr2. although this gene cluster is not conserved in all aspergilli, laccases are critical for melanization in all species examined. here we show that the expression of a. fumiga ...201324123270
contributions of aspergillus fumigatus atp-binding cassette transporter proteins to drug resistance and virulence.in yeast cells such as those of saccharomyces cerevisiae, expression of atp-binding cassette (abc) transporter proteins has been found to be increased and correlates with a concomitant elevation in azole drug resistance. in this study, we investigated the roles of two aspergillus fumigatus proteins that share high sequence similarity with s. cerevisiae pdr5, an abc transporter protein that is commonly overproduced in azole-resistant isolates in this yeast. the two a. fumigatus genes encoding the ...201324123268
exopolysaccharides and antimicrobial biosurfactants produced by paenibacillus macerans tku029.paenibacillus macerans tku029 can produce exopolysaccharides (epss; 3.46 g/l) and a biosurfactant (1.78 g/l) in a medium with 2 % (w/v) squid pen powder as the sole carbon/nitrogen source. the biosurfactant can reduce the surface tension of water from 72.30 to 35.34 mn/m at a concentration of 2.76 g/l and reach an emulsification index of 56 % after a 24-h reaction with machine oil. this biosurfactant is stable at 121 °c for 20 min, over a ph range from 3 to 11, and in <5 % salt solutions. it als ...201424122708
distinct mechanisms for spiro-carbon formation reveal biosynthetic pathway crosstalk.spirotryprostatins, an indole alkaloid class of nonribosomal peptides isolated from aspergillus fumigatus, are known for their antimitotic activity in tumor cells. because spirotryprostatins and many other chemically complex spiro-carbon-bearing natural products exhibit useful biological activities, identifying and understanding the mechanism of spiro-carbon biosynthesis is of great interest. here we report a detailed study of spiro-ring formation in spirotryprostatins from tryprostatins derived ...201324121553
gfsa encodes a novel galactofuranosyltransferase involved in biosynthesis of galactofuranose antigen of o-glycan in aspergillus nidulans and aspergillus fumigatus.the cells walls of filamentous fungi in the genus aspergillus have galactofuranose (galf)-containing polysaccharides and glycoconjugates, including o-glycans, n-glycans, fungal-type galactomannan and glycosylinositolphosphoceramide, which are important for cell wall integrity. here, we attempted to identify galactofuranosyltransferases that couple galf monomers onto other wall components in aspergillus nidulans. using reverse-genetic and biochemical approaches, we identified that the an8677 gene ...201324118544
the fumagillin gene cluster, an example of hundreds of genes under vea control in aspergillus fumigatus.aspergillus fumigatus is the causative agent of invasive aspergillosis, leading to infection-related mortality in immunocompromised patients. we previously showed that the conserved and unique-to-fungi vea gene affects different cell processes such as morphological development, gliotoxin biosynthesis and protease activity, suggesting a global regulatory effect on the genome of this medically relevant fungus. in this study, rna sequencing analysis revealed that vea controls the expression of hund ...201324116213
coinfection of pneumocystis jirovecii and invasive pulmonary aspergillosis in an immunocompromised patient: a diagnostic challenge.invasive infections caused by aspergillus fumigatus as well as pneumocystis pneumonia are serious and often lethal diseases in severely immunocompromised patients.201324107913
genomic identification of potential targets unique to candida albicans for the discovery of antifungal agents.despite of modern antifungal therapy, the mortality rates of invasive infection with human fungal pathogen candida albicans are up to 40%. studies suggest that drug resistance in the three most common species of human fungal pathogens viz., c. albicans, aspergillus fumigatus (causing mortality rate up to 90%) and cryptococcus neoformans (causing mortality rate up to 70%) is due to mutations in the target enzymes or high expression of drug transporter genes. drug resistance in human fungal pathog ...201424102473
the complexity of aging: cancer risk among elderly people and infectious risk among those with cancer.aging is associated with a reduced capability of the immune system to adequately respond to pathogens and to prevent tumor formation. as a consequence of immunosenescence, older people have a higher risk to develop infections as well as cancer. in addition, cancer itself may expose old patients to infections, including opportunistic infections, i.e. pseudomonas aeruginosa, aspergillus fumigatus and cytomegalovirus infection. patients with hematologic malignancies have a higher risk than patients ...201324102281
nkt cells: the smoking gun in fungal-induced asthma?aspergillus fumigatus is a fungus that is associated with a severe form of asthma, although the precise immunological basis for this disease is unclear. a new study in mice shows that natural killer t (nkt) cells are crucial for progression of a. fumigatus–induced asthma and also identifies a glycolipid antigen from this fungus that seems to drive this nkt cell–mediated inflammatory response (pages 1297–1304).201324100979
isavuconazole (bal4815) pharmacodynamic target determination in an in vivo murine model of invasive pulmonary aspergillosis against wild-type and cyp51 mutant isolates of aspergillus fumigatus.invasive pulmonary aspergillosis (ipa) continues to rise in concert with increasing numbers of immune suppression techniques to treat other medical conditions and transplantation. despite these advances, morbidity and mortality rates remain unacceptably high. one strategy used to optimize outcomes is antifungal pharmacodynamic (pd) examination. we explored the pharmacodynamics of a new triazole in development, isavuconazole, in a murine neutropenic ipa model. ten a. fumigatus isolates were used, ...201324100500
a functional and structural study of the major metalloprotease secreted by the pathogenic fungus aspergillus fumigatus.fungalysins are secreted fungal peptidases with the ability to degrade the extracellular matrix proteins elastin and collagen and are thought to act as virulence factors in diseases caused by fungi. fungalysins constitute a unique family among zinc-dependent peptidases that bears low sequence similarity to known bacterial peptidases of the thermolysin family. the crystal structure of the archetype of the fungalysin family, aspergillus fumigatus metalloprotease (afumep), has been obtained for the ...201324100314
antifungal dimeric chalcone derivative kamalachalcone e from mallotus philippinensis.from the red coloured extract (kamala) prepared through acetone extraction of the fresh whole uncrushed fruits of mallotus philippinensis, one new dimeric chalcone (1) along with three known compounds 1-(5,7-dihydroxy-2,2,6-trimethyl-2h-1-benzopyran-8-yl)-3-phenyl-2-propen-1-one (2), rottlerin (3) and 4'-hydroxyrottlerin (4) were isolated. the structure of compound 1 was elucidated by 1d and 2d nmr analyses that included hsqc, hmbc, cosy and roesy experiments along with the literature comparison ...201424099509
transcriptional activation of heat shock protein 90 mediated via a proximal promoter region as trigger of caspofungin resistance in aspergillus fumigatus.invasive aspergillosis is a deadly infection for which new antifungal therapies are needed. heat shock protein 90 (hsp90) is an essential chaperone in aspergillus fumigatus representing an attractive antifungal target. using a thiamine-repressible promoter (pthia), we showed that genetic repression of hsp90 significantly reduced virulence in a murine model of invasive aspergillosis. moreover, substituting the a. fumigatus hsp90 promoter with 2 artificial promoters (potef, pthia) and the candida ...201424096332
fatal-mixed cutaneous zygomycosis-aspergillosis: a case report.mucorales and aspergillus are molds responsible for infections in immunocompromised patients. in this report, we describe a case of a rare extensively mixed cutaneous infection caused by lichtheimia ramosa, aspergillus fumigatus and aspergillus terreus in a neutropenic patient suffering from an acute leukemia. the fatal outcome of this patient can be attributed to its hematologic malignancy, the extensive nature of the lesions and the resistance of the strains to antifungals.201324085614
effect of physical and chemical properties of oil palm empty fruit bunch, decanter cake and sago pith residue on cellulases production by trichoderma asperellum upm1 and aspergillus fumigatus upm2.the effect of cultivation condition of two locally isolated ascomycetes strains namely trichoderma asperellum upm1 and aspergillus fumigatus upm2 were compared in submerged and solid state fermentation. physical evaluation on water absorption index, solubility index and chemical properties of lignin, hemicellulose and cellulose content as well as the cellulose structure on crystallinity and amorphous region of treated oil palm empty fruit bunch (opefb) (resulted in partial removal of lignin), sa ...201424085387
azole-resistant aspergillus fumigatus with the environmental tr46/y121f/t289a mutation in india. 201424084639
synthesis and biological evaluation of potent antifungal agents.the last two decades are characterized by major increases in the incidence of systemic fungal infections caused by the yeast candida albicans, particularly in immunocompromised patients. on the other hand it was observed the increased number of pathogenic microorganisms with multiple resistance to drugs. also there is a big variety of drugs for the treatment of candidiasis, only two drugs are used for the treatment of infections from aspergillus fumigatus. taking into account that the long term ...201324083791
prototype of an intertwined secondary-metabolite supercluster.the hallmark trait of fungal secondary-metabolite gene clusters is well established, consisting of contiguous enzymatic and often regulatory gene(s) devoted to the production of a metabolite of a specific chemical class. unexpectedly, we have found a deviation from this motif in a subtelomeric region of aspergillus fumigatus. this region, under the control of the master regulator of secondary metabolism, laea, contains, in its entirety, the genetic machinery for three natural products (fumitremo ...201324082142
role of ser-257 in the sliding mechanism of nadp(h) in the reaction catalyzed by the aspergillus fumigatus flavin-dependent ornithine n5-monooxygenase sida.sida (siderophore a) is a flavin-dependent n-hydroxylating monooxygenase that is essential for virulence in aspergillus fumigatus. sida catalyzes the nadph- and oxygen-dependent formation of n(5)-hydroxyornithine. in this reaction, nadph reduces the flavin, and the resulting nadp(+) is the last product to be released. the presence of nadp(+) is essential for activity, as it is required for stabilization of the c4a-hydroperoxyflavin, which is the hydroxylating species. as part of our efforts to d ...201324072704
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