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the impact of weakly bound ⁸⁹zr on preclinical studies: non-specific accumulation in solid tumors and aspergillus infection.preclinical studies involving (89)zr often report significant bone accumulation, which is associated with dissociation of the radiometal from the tracer. however, experiments determining the uptake of unbound (89)zr in disease models are not performed as routine controls. the purpose of the present study was to investigate the impact of free or weakly bound (89)zr on pet quantifications in disease models, in order to determine if such control experiments are warranted.201525583221
purification, immobilization, and biochemical characterization of l-arginine deiminase from thermophilic aspergillus fumigatus kj434941: anticancer activity in vitro.l-arginine deiminase (adi) has a powerful anticancer activity against various tumors, via arginine depletion, arresting the cell cycle at g1 phase. however, the current clinically tried bacterial adi displayed a higher antigenicity and lower thermal stability. thus, our objective was to purify and characterize this enzyme from thermophilic fungi, to explore its catalytic and antigenic properties for therapeutic uses. adi was purified from thermophilic aspergillus fumigatus kj434941 to its electr ...201625582958
transcriptome analysis of cyclic amp-dependent protein kinase a-regulated genes reveals the production of the novel natural compound fumipyrrole by aspergillus fumigatus.aspergillus fumigatus is an opportunistic human pathogenic fungus causing life-threatening infections in immunocompromised patients. adaptation to different habitats and also virulence of the fungus depends on signal perception and transduction by modules such as the cyclic amp-dependent protein kinase a (pka) pathway. here, by transcriptome analysis, 632 differentially regulated genes of this important signaling cascade were identified, including 23 putative transcriptional regulators. the high ...201525582336
a monoclonal antibody against glycoproteins of aspergillus fumigatus shows anti-adhesive potential.there has been an increase in the cases of fungal resistance against many antifungal drugs and an effective alternative mode in the form of immunotherapy is being considered as new hope. the adhesion of aspergillus fumigatus conidia to the host components is one of the prime factors to cause aspergillosis. carbohydrate components or glycoproteins present on the cell surface play an important role in interaction of the organism to the host and leads to adhesion. any substance which is capable of ...201525578403
mixing compatibilities of aspergillus and american cockroach allergens with other high-protease fungal and insect extracts.recent studies have shown that alternaria and german cockroach allergens can be degraded by endogenous proteases from other insect and fungal extracts when combined for immunotherapy, but data supporting the compatibilities of other high-protease products in comparable mixtures have not been reported.201525578248
in-vitro assessment of the probiotic potential of lactobacillus plantarum kcc-24 isolated from italian rye-grass (lolium multiflorum) forage.the aim of the present study was to determine the probiotic potential of the lactic acid bacteria lactobacillus plantarum kcc-24 (l. plantarum kcc-24), that was isolated and characterized from italian ryegrass (lolium multiflorum) forage. the following experiments were performed to assess the probiotic characteristics such as antifungal activity, antibiotic susceptibility, resistance to low ph, stimulated gastric juice and bile salts, proteolytic activity, auto-aggregation, cell surface hydropho ...201525576238
validation of a new aspergillus real-time pcr assay for direct detection of aspergillus and azole resistance of aspergillus fumigatus on bronchoalveolar lavage fluid.azole resistance in aspergillus fumigatus is increasingly reported. here, we describe the validation of the aspergenius, a new multiplex real-time pcr assay consisting of two multiplex real-time pcrs, one that identifies the clinically relevant aspergillus species, and one that detects the tr34, l98h, t289a, and y121f mutations in cyp51a and differentiates susceptible from resistant a. fumigatus strains. the diagnostic performance of the aspergenius assay was tested on 37 bronchoalveolar lavage ...201525568431
cd8(+) t cells implicated in the pathogenesis of allergic fungal rhinosinusitis.fungi in paranasal sinuses are characteristic and considered a major pathogenic factor in a subset of chronic rhinosinusitis (crs) patients, known as allergic fungal rhinosinusitis (afrs). cd8(+) t cells are enriched in afrs sinuses but their role in fungal-specific responses is unknown. alternaria alternata- and aspergillus fumigatus-specific t lymphocyte responses were investigated in 6 afrs patients, 10 eosinophilic mucus crs (emcrs) patients, 10 crs with nasal polyps (crswnps) patients, 6 al ...201425565051
conserved and varied dinucleotide sequences in the genomes of three aspergillus species.both guanine-cytosine content and nucleosome occupancy are higher in exons than in introns. in this study, the association between the frequencies of the dinucleotide sequences and the nucleosome occupancy of the exons and introns of the genes of aspergillus fumigatus, aspergillus nidulans, and aspergillus oryzae was studied. the frequency of the dinucleotide sequences aa (tt), at, and ta in the introns was more than that in the exons. in addition, the frequency of these sequences in the regions ...201425564023
calcium signaling mediates antifungal activity of triazole drugs in the aspergilli.azoles are widely applied and largely effective as antifungals; however, the increasing prevalence of clinically resistant isolates has yet to be matched by approaches to improve the efficacy of antimicrobial therapy. in this study, using the model fungus aspergillus nidulans and one of the most common human pathogen aspergillus fumigatus as research materials, we present the evidence that calcium signaling is involved in the azole-antifungals-induced stress-response reactions. in normal media, ...201525554700
new ikarugamycin derivatives with antifungal and antibacterial properties from streptomyces zhaozhouensis.a bioassay guided fractionation of the ethyl acetate extract from culture broths of the strain streptomyces zhaozhouensis ca-185989 led to the isolation of three new polycyclic tetramic acid macrolactams (1-3) and four known compounds. all the new compounds were structurally related to the known streptomyces metabolite ikarugamycin (4). their structural elucidation was accomplished using a combination of electrospray-time of flight mass spectrometry (esi-tof ms) and 1d and 2d nmr analyses. compo ...201425551780
toxicity and efficacy differences between liposomal amphotericin b formulations in uninfected and aspergillus fumigatus infected mice.because of the reduced toxicity associated with liposomal amphotericin b preparations, different amphotericin b liposome products have been made. in the present study, we compared the amphotericin b liposomal formulations, ambisome(®) (ambi) and lambin(®) (lbn), in uninfected and aspergillus fumigatus infected mice, using several in vitro and in vivo toxicity and efficacy assays. the results showed that the formulations were significantly different, with lbn 1.6-fold larger than ambi. lbn was al ...201525550388
the crosstalk between tlr2 and nod2 in aspergillus fumigatus keratitis.innate immunity is considered to be critical in the pathogenesis of fungal keratitis. pattern recognition receptors (prrs) recognize conserved microbial structures called pathogen-associated molecular patterns (pamps), thereby initiating the innate immunity. toll-like receptors (tlrs) and nucleotide-binding oligomerization domain (nod)-like receptors (leucine-rich repeat-containing receptors, nlrs) are two major prr families. the crosstalk between tlr2 and nod2 is not completely understood, and ...201525549945
resistin-like molecule-β (relm-β) targets airways fibroblasts to effect remodelling in asthma: from mouse to man.relm-β has been implicated in airways inflammation and remodelling in murine models. its possible functions in human airways are largely unknown. the aim was to address the hypothesis that relm-β plays a role in extracellular matrix deposition in asthmatic airways.201525545115
does farm fungicide use induce azole resistance in aspergillus fumigatus?azole resistance of aspergillus fumigatus isolates has been reported worldwide and it would appear to be mainly due to a point mutation in the 14α-sterol demethylase (cyp51a) gene, which is the target enzyme for azoles. the mutation has been confirmed in isolates from patients who received long-term itraconazole (itz) therapy and from agricultural fields where high levels of azole fungicides were employed. however, the relationship between farm environments and azole-resistant a. fumigatus has n ...201525541556
maldi-tof mass spectrometry for rapid identification of clinical fungal isolates based on ribosomal protein biomarkers.this study aimed to evaluate the identification of clinical fungal isolates (yeast and molds) by protein profiling using matrix-assisted laser desorption ionization-time of flight mass spectrometry (maldi-tof/ms). a total of 125 clinical fungal culture isolates (yeast and filamentous fungi) were collected. the test set included 88 yeast isolates (candida albicans, candida glabrata, candida guilliermondii, candida kefyr, candida krusei, candida parapsilosis, candida rugosa, candida tropicalis and ...201525541362
aspergillus fumigatus transcriptome response to a higher temperature during the earliest steps of germination monitored using a new customized expression microarray.aspergillus fumigatus is considered to be the most prevalent airborne pathogenic fungus and can cause invasive diseases in immunocompromised patients. it is known that its virulence is multifactorial, although the mechanisms of pathogenicity remain unclear. with the aim of improving our understanding of these mechanisms, we designed a new expression microarray covering the entire genome of a. fumigatus. in this first study, we analysed the transcriptomes of this fungus at the first steps of germ ...201525536999
divergent targets of aspergillus fumigatus acuk and acum transcription factors during growth in vitro versus invasive disease.in aspergillus nidulans, the acuk and acum transcription factors form a complex that regulates gluconeogenesis. in aspergillus fumigatus, acum governs gluconeogenesis and iron acquisition in vitro and virulence in immunosuppressed mice. however, the function of acuk was previously unknown. through in vitro studies, we found that a. fumigatus δacuk single and δacuk δacum double mutants had impaired gluconeogenesis and iron acquisition, similar to the δacum mutant. also, the δacuk, δacum, and δacu ...201525534941
the apses family proteins in fungi: characterizations, evolution and functions.the apses protein family belongs to transcriptional factors of the basic helix-loop-helix (bhlh) class, the originally described members (apses: asm1p, phd1p, sok2p, efg1p and stuap) are used to designate this group of proteins, and they have been identified as key regulators of fungal development and other biological processes. apses proteins share a highly conserved dna-binding domain (apses domain) of about 100 amino acids, whose central domain is predicted to form a typical bhlh structure. b ...201525534868
posaconazole prophylaxis in experimental azole-resistant invasive pulmonary aspergillosis.we investigated the efficacy of posaconazole prophylaxis in preventing invasive aspergillosis due to azole-resistant aspergillus fumigatus isolates. using a neutropenic murine model of pulmonary infection, posaconazole prophylaxis was evaluated using three isogenic clinical isolates, with posaconazole mics of 0.063 mg/liter (wild type), 0.5 mg/liter (f219i mutation), and 16 mg/liter. a fourth isolate harboring tr34/l98h (mic of 0.5 mg/liter) was also tested. posaconazole prophylaxis was effectiv ...201525534731
redox metabolites signal polymicrobial biofilm development via the napa oxidative stress cascade in aspergillus.filamentous fungi and bacteria form mixed-species biofilms in nature and diverse clinical contexts. they secrete a wealth of redox-active small molecule secondary metabolites, which are traditionally viewed as toxins that inhibit growth of competing microbes.201525532893
genetic engineering activates biosynthesis of aromatic fumaric acid amides in the human pathogen aspergillus fumigatus.the aspergillus fumigatus nonribosomal peptide synthetase ftpa is among the few of this species whose natural product has remained unknown. both ftpa adenylation domains were characterized in vitro. fumaric acid was identified as preferred substrate of the first and both l-tyrosine and l-phenylalanine as preferred substrates of the second adenylation domain. genetically engineered a. fumigatus strains expressed either ftpa or the regulator gene ftpr, encoded in the same cluster of genes, under t ...201525527545
antifungal innate immunity: recognition and inflammatory networks.a large variety of fungi are present in the environment, among which a proportion colonizes the human body, usually without causing any harm. however, depending on the host immune status, commensals can become opportunistic pathogens that induce diseases ranging from superficial non-harmful infection to life-threatening systemic disease. the interplay between the host and the fungal commensal flora is being orchestrated by an efficient recognition of the microorganisms, which in turn ensures a p ...201525527294
a novel fungus concentration-dependent rat model for acute invasive fungal rhinosinusitis: an experimental study.acute invasive fungal rhinosinusitis is a lethal infectious process afflicting immunocompromised individuals. knowledge about this disease is still limited due to the scarcity of animal models designed to study the pathogenesis of this infection. mast cells are tissue-resident immune cells that participate in a variety of allergic and inflammatory conditions. limited attention has been given to the role of mast cells in acute invasive fungal rhinosinusitis. therefore, the objectives of this stud ...201425526739
gas6'ing the innate immune response during experimental asthma.growth arrest-specific gene 6 (gas6) binds tyro3, axl, and mertk (tam) receptors and exerts prominent effects in many diseases, but little is known about its role in asthma. herein, we examined the role of gas6 and tam receptors differentially in an experimental asthma model driven by aspergillus fumigatus. a. fumigatus-sensitized mice were challenged with live a. fumigatus conidia, and airway hyperresponsiveness and airway remodeling were determined 28 days later. when administered to mice from ...201425525737
prevalence of allergic fungal rhinosinusitis among patients with chronic rhinosinusitis with or without nasal polyposis who underwent endonasal sinus surgery in northwestern turkey.this study aims to evaluate the prevalence of allergic fungal rhinosinusitis in chronic rhinosinusitis patients in the northwest of turkey.201625513868
bronchomediastinal fistula caused by endobronchial aspergilloma.endobronchial aspergilloma is a rare condition affecting immunocompromised patients. we present three cases resulting in airway fistulae.201525513736
multilaboratory testing of antifungal drug combinations against candida species and aspergillus fumigatus: utility of 100 percent inhibition as the endpoint.four laboratories tested three isolates of candida species and two isolates of aspergillus fumigatus using 96-well plates containing combinations of amphotericin b, anidulafungin, caspofungin, micafungin, fluconazole, itraconazole, posaconazole, and voriconazole. the majority of summation fractional inhibitory concentration indices (σfici) based on the lowe additivity formula suggested indifferent drug interactions (σfici > 0.5 and ≤4.0) and no instance of drug antagonism (σfici > 4.0). the intr ...201525512402
[application of detecting mannose-binding lectins in pulmonary aspergillosis in rats].to explore the effects of mannose-binding lectins (mbl) in pulmonary aspergillosis.201425511601
[molecular markers: an important tool in the diagnosis, treatment and epidemiology of invasive aspergillosis].increase in the incidence of invasive aspergillosis has represented a difficult problem for management of patients with this infection due to its high rate of mortality, limited knowledge concerning its diagnosis, and therapeutic practice. the difficulty in management of patients with aspergillosis initiates with detection of the fungus in the specimens of immunosuppressed patients infected with aspergillus fumigatus; in addition, difficulty exists in terms of the development of resistance to an ...201425510798
fungal isolation from disinfectant solutions of contact lens storage cases among asymptomatic users.to investigate the incidence of fungal contamination of store disinfectant solutions contained in contact lens storage cases belonging to asymptomatic contact lens users.201525503912
[qualitative fungal composition of services at risk of nosocomial infections at aristide le dantec hospital (dakar)].in hospitals, the quality control of the air is a key element. indeed airborne fungi constitute a real danger for patients hospitalized in wards at risk of nosocomial infections especially when they are immunocompromised.201525499807
production of a chaetomium globosum enolase monoclonal antibody.chaetomium globosum is a hydrophilic fungal species and a contaminant of water-damaged building materials in north america. methods to detect chaetomium species include subjective identification of ascospores, viable culture, or molecular-based detection methods. in this study, we describe the production and initial characterization of a monoclonal antibody (mab) for c. globosum enolase. mab 1c7, a murine igg1 isotype mab, was produced and reacted with recombinant c. globosum enolase (rcgeno) in ...201425495488
susceptibility breakpoints and target values for therapeutic drug monitoring of voriconazole and aspergillus fumigatus in an in vitro pharmacokinetic/pharmacodynamic model--authors' response. 201525488075
cutaneous, respiratory and hepatic aspergillosis in brazilian white pekin mallards (anas platyrhynchos).aspergillosis is one of the most frequent mycosis affecting avian species. here is reported an outbreak of aspergillosis affecting 60-day-old white pekin mallards (anas platyrhynchos). about 10% of animals in a lot of 200 mallards from a commercial husbandry presented respiratory disorders and skin lesions at slaughter. three out of 13 animals sent to diagnosis showed, simultaneously, airsacculitis, lung and liver presenting white nodules with variable diameters and elevated, yellowish brown, cr ...201525481845
production of bioethanol using agricultural waste: banana pseudo stem.india is amongst the largest banana (musa acuminata) producing countries and thus banana pseudo stem is commonly available agricultural waste to be used as lignocellulosic substrate. present study focuses on exploitation of banana pseudo stem as a source for bioethanol production from the sugars released due to different chemical and biological pretreatments. two fungal strains aspergillus ellipticus and aspergillus fumigatus reported to be producing cellulolytic enzymes on sugarcane bagasse wer ...201425477922
site-directed mutagenesis switching a dimethylallyl tryptophan synthase to a specific tyrosine c3-prenylating enzyme.the tryptophan prenyltransferases fgapt2 and 7-dmats (7-dimethylallyl tryptophan synthase) from aspergillus fumigatus catalyze c(4)- and c(7)-prenylation of the indole ring, respectively. 7-dmats was found to accept l-tyrosine as substrate as well and converted it to an o-prenylated derivative. an acceptance of l-tyrosine by fgapt2 was also observed in this study. interestingly, isolation and structure elucidation revealed the identification of a c(3)-prenylated l-tyrosine as enzyme product. mol ...201525477507
suppression of epithelial signal transducer and activator of transcription 1 activation by extracts of aspergillus fumigatus.aspergillus fumigatus (af) is often pathogenic in immune-deficient individuals and can cause life-threatening infections such as invasive aspergillosis. the pulmonary epithelial response to af infection and the signaling pathways associated with it have not been completely studied. beas-2b cells or primary human bronchial epithelial cells were exposed to extracts of af and challenged with ifn-β or the toll-like receptor 3 agonist double-stranded rna (dsrna). cytokine release (b-cell activating f ...201525474274
allergic bronchopulmonary aspergillosis presenting with a pulmonary mass mimicking lung cancer.a 48-year-old man with a history of asthma visited our hospital for the investigation of a high density mass at the right hilum. laboratory data revealed elevated serum carcinoembryonic antigen. a bronchoscopy was performed to rule out lung cancer; however, mucoid impaction was found without malignant or bacterial cells. on the basis of peripheral blood eosinophilia, elevated total serum ige, and immediate cutaneous reactivity to aspergillus fumigatus, he was diagnosed with allergic bronchopulmo ...201325473526
tacrolimus (fk506) suppresses trem-1 expression at an early but not at a late stage in a murine model of fungal keratitis.to investigate the efficacy and mechanism of tacrolimus(fk506), which is a novel macrolide immunosuppressant, in inhibiting triggering receptor expressed on myeloid cells-1 (trem-1) expression in a murine keratitis model induced by aspergillus fumigatus.201425464008
molecular epidemiology of aspergillus collected from cystic fibrosis patients.aspergillus respiratory infection is a common complication in cystic fibrosis (cf) and is associated with loss of pulmonary function and allergic disease.201525459562
the role of atfa and hog mapk pathway in stress tolerance in conidia of aspergillus fumigatus.aspergillus fumigatus is a life-threatening pathogenic fungus, whose conidium is the infectious agent of aspergillosis. to better understand the mechanism underlying the long-term viability of conidia, we characterized a bzip transcription factor, atfa, with special reference to stress-tolerance in conidia. the atfa deletion mutant conidia showed significant sensitivity to high temperature and oxidative stress. the trehalose content that accumulated in conidia was reduced in the mutant conidia. ...201425459537
gliotoxin from aspergillus fumigatus reverses epithelial to mesenchymal transition: implications in renal fibrosis.fibrosis is generally characterized by an excessive accumulation and deposition of extracellular matrix (ecm) that progressively leads to the destruction of functional nephrons of the kidney. current study is aimed to propose a probable antifibrotic mechanism of gliotoxin, isolated from marine aspergillus fumigatus strain, in proximal tubule renal epithelial cells by inhibiting hif-1α, ang-ii and nf-κb in a dose dependent manner. gtx at a concentration of 1.6 ng/ml also showed more than 80% cell ...201525455839
amphotericin-b entrapped lecithin/chitosan nanoparticles for prolonged ocular application.fungal keratitis is the major cause of vision loss worldwide. amphotericin-b is considered as the drug of choice for fungal infections. however, its use in ophthalmic drug delivery is limited by the low precorneal residence at ocular surface as a result of blinking reflex, tear turnover and nasopharyngeal drainage. we report amphotericin-b loaded lecithin/chitosan nanoparticles for prolonged ocular application. the prepared nanoparticles were in the size range of 161.9-230.5 nm, entrapment effic ...201525453292
empyema necessitatis due to aspergillus fumigatus.we present an extremely rare case of empyema necessitatis secondary to aspergillus fumigatus infection. a 58-year-old woman presented to our hospital with a painful skin rash on the right thorax. three fistulas communicating with the pleural space were found. since she did not show a clinical improvement despite antituberculous and antibacterial treatment, we looked for other causes. pleural fungus culture showed a. fumigatus and chest wall biopsy revealed numerous fungal hyphae. treatment with ...201425452298
cryptococcus neoformans yap1 is required for normal fluconazole and oxidative stress resistance.cryptococcus neoformans is a pathogen that is the most common cause of fungal meningitis. as with most fungal pathogens, the most prevalent clinical antifungal used to treat cryptococcosis is orally administered fluconazole. resistance to this antifungal is an increasing concern in treatment of fungal disease in general. our knowledge of the specific determinants involved in fluconazole resistance in cryptococcus is limited. here we report the identification of an important genetic determinant o ...201525445311
contamination of a purified water system by aspergillus fumigatus in a new endoscopy reprocessing unit.use of purified water for the final rinse stage of disinfected endoscopes is an important element of quality control. we describe the detection and management of aspergillus fumigatus contamination of a new reverse osmosis unit supplying 10 automated endoscope reprocessor basins. prompt detection and reaction to this contaminant were possible because of the introduction of a comprehensive program for microbiological monitoring of rinse waters, which included total viable counts, endotoxin, condu ...201425444308
[nocardia farcinica lung infection in a patient with cystic fibrosis and a lung transplant].patients with cystic fibrosis have a higher risk of developing chronic respiratory infectious diseases. the nocardia farcinica lung infection is rare in this group of patients, and there are limited publications about this topic. its diagnosis is complex, due to the clinical and the radiology signs being non-specific. identification of the agent responsible in the sputum culture is occasionally negative. it is a slow growing organism and for this reason treatment is delayed, which can lead to an ...201525443661
antifungal therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.allergic bronchopulmonary aspergillosis (abpa) is an allergic reaction to colonisation of the lungs with the fungus aspergillus fumigatus and affects around 10% of people with cystic fibrosis. abpa is associated with an accelerated decline in lung function. high doses of corticosteroids are the main treatment for abpa; although the long-term benefits are not clear, their many side effects are well-documented. a group of compounds, the azoles, have activity against aspergillus fumigatus and have ...201425431975
some strychnos spinosa (loganiaceae) leaf extracts and fractions have good antimicrobial activities and low cytotoxicities.strychnos spinosa lam. is a deciduous tree used in traditional medicine to treat infectious diseases. this study is designed to determine the antimicrobial, antioxidant and cytotoxic activities of extracts and fractions from leaves of s. spinosa.201425428165
gardening can induce pulmonary failure: aspergillus ards in an immunocompetent patient, a case report.acute aspergillus fumigatus infection in immunocompetent patients is rare. this is the first known case of a patient who survived aspergillus sepsis after being treated early with veno-venous extracorporeal membrane (ecmo) and antifungal therapy.201425425351
aspergillus fumigatus devoid of cell wall β-1,3-glucan is viable, massively sheds galactomannan and is killed by septum formation inhibitors.echinocandins inhibit β-1,3-glucan synthesis and are one of the few antimycotic drug classes effective against aspergillus spp. in this study, we characterized the β-1,3-glucan synthase fks1 of aspergillus fumigatus, the putative target of echinocandins. data obtained with a conditional mutant suggest that fks1 is not essential. in agreement, we successfully constructed a viable δfks1 deletion mutant. lack of fks1 results in characteristic growth phenotypes similar to wild type treated with echi ...201525425041
suppurative thyroiditis due to aspergillosis: a case report.aspergillus, a nosocomial agent, is the most common fungal cause of suppurative thyroiditis. most patients with aspergillus thyroiditis have disseminated infection, primarily with lung compromise. late diagnosis and treatment, severity of immunosuppressive state and thyroid hormone overload contribute to extremely high mortality rates.201425412755
contributions of unique active site residues of eukaryotic udp-galactopyranose mutases to substrate recognition and active site dynamics.udp-galactopyranose mutase (ugm) catalyzes the interconversion between udp-galactopyranose and udp-galactofuranose. absent in humans, galactofuranose is found in bacterial and fungal cell walls and is a cell surface virulence factor in protozoan parasites. for these reasons, ugms are targets for drug discovery. here, we report a mutagenesis and structural study of the ugms from aspergillus fumigatus and trypanosoma cruzi focused on active site residues that are conserved in eukaryotic ugms but a ...201425412209
microsatellite (straf) genotyping cannot differentiate between invasive and colonizing aspergillus fumigatus isolates.we studied whether short tandem repeats of aspergillus fumigatus (straf) can differentiate between invasive and colonizing genotypes of a. fumigatus. of the 395 genotypes detected (n = 1,373 isolates), 50 were clusters and 24 (6% of all genotypes) involved the patients with invasive aspergillosis and those colonized with a. fumigatus, indicating that genotyping cannot discriminate between invasive and colonizing isolates.201525411179
interference of aspergillus fumigatus with the immune response.aspergillus fumigatus is a saprotrophic filamentous fungus and also the most prevalent airborne fungal pathogen of humans. depending on the host's immune status, the variety of diseases caused by a. fumigatus ranges from allergies in immunocompetent hosts to life-threatening invasive infections in patients with impaired immunity. in contrast to the majority of other aspergillus species, which are in most cases nonpathogenic, a. fumigatus features an armory of virulence determinants to establish ...201525404120
heterologous expression of gaeumannomyces graminis lipoxygenase in aspergillus nidulans.aspergillus sp. contain ppo genes coding for ppo enzymes that produce oxylipins from polyunsaturated fatty acids. these oxylipins function as signal molecules in sporulation and influence the asexual to sexual ratio of aspergillus sp. fungi like aspergillus nidulans and aspergillus niger contain just ppo genes where the human pathogenic aspergillus flavus and aspergillus fumigatus contain ppo genes as well as lipoxygenases. lipoxygenases catalyze the synthesis of oxylipins and are hypothesized t ...201425401068
structural and biochemical characterization of the dual substrate recognition of the (r)-selective amine transaminase from aspergillus fumigatus.chiral amines are important precursors for the pharmaceutical and fine-chemical industries. because of this, the demand for enantiopure amines is currently increasing. amine transaminases can produce a large spectrum of chiral amines in the (r)- or (s)-configuration, depending on their substrate scope and stereo-preference, by converting a prochiral ketone into the chiral amine while using alanine as the amine donor producing pyruvate as an α-keto acid product. in order to guide the protein engi ...201525400251
molecular identification of fungi found on decomposed human bodies in forensic autopsy cases.to investigate which fungi can be found during forensic autopsies, a pubmed literature review was done in regard to fungal growth on decomposed human bodies. unfortunately, the existing data is limited and not all fungi were identified to the species level. we, therefore, collected skin samples with macroscopically visible fungal growth from 23 autopsy cases in germany and identified the fungi to the species level by molecular methods. the identified species included aspergillus fumigatus and ca ...201525398636
mold contamination in a controlled hospital environment: a 3-year surveillance in southern italy.environmental monitoring of airborne filamentous fungi is necessary to reduce fungal concentrations in operating theaters and in controlled environments, and to prevent infections. the present study reports results of a surveillance of filamentous fungi carried out on samples from air and surfaces in operating theaters and controlled environments in an italian university hospital.201425398412
identification and characterization of an antifungal protein, afafpr9, produced by marine-derived aspergillus fumigatus r9.a fungal strain, r9, was isolated from the south atlantic sediment sample and identified as aspergillus fumigatus. an antifungal protein, afafpr9, was purified from the culture supernatant of aspergillus fumigatus r9. afafpr9 was identified to be restrictocin, which is a member of the ribosome-inactivating proteins (rips), by maldi-tof-tof-ms. afafpr9 displayed antifungal activity against plant pathogenic fusarium oxysporum, alternaria longipes, colletotrichum gloeosporioides, paecilomyces vario ...201525394604
bilateral simultaneous endogenous aspergillus endophthalmitis in an immunocompetent patient.to report a case of bilateral endogenous aspergillus endophthalmitis in an immunocompetent patient.201025390109
perturbations in small molecule synthesis uncovers an iron-responsive secondary metabolite network in aspergillus fumigatus.iron plays a critical role in survival and virulence of the opportunistic pathogen aspergillus fumigatus. two transcription factors, the gata-factor srea and the bzip-factor hapx oppositely monitor iron homeostasis with hapx activating iron acquisition pathways (e.g., siderophores) and shutting down iron consumptive pathways (and srea) during iron starvation conditions whereas srea negatively regulates hapx and corresponding pathways during iron sufficiency. recently the non-ribosomal peptide, h ...201425386169
a report of a successfully treated case of abpa in an hiv-infected individual.aspergillus fumigatus is a ubiquitous fungus responsible for a variety of pulmonary diseases, ranging from infection of a pre-existing cavity as in aspergilloma to highly invasive disease in immunocompromised hosts. allergic bronchopulmonary aspergillosis (abpa) is a hypersensitivity response mounted against antigens of a. fumigatus manifesting as poorly controlled asthma and bronchiectasis. although abpa is not uncommon, occurrence of abpa in hiv-affected individuals is distinctly rare. we desc ...201425385562
fungal pathogens: survival and replication within macrophages.the innate immune system is a critical line of defense against pathogenic fungi. macrophages act at an early stage of infection, detecting and phagocytizing infectious propagules. to avoid killing at this stage, fungal pathogens use diverse strategies ranging from evasion of uptake to intracellular parasitism. this article will discuss five of the most important human fungal pathogens (candida albicans, aspergillus fumigatus, cryptococcus neoformans, coccidiodes immitis, and histoplasma capsulat ...201425384769
aspergillus tracheobronchitis, bronchopleural fistula and empyema after lobectomy for aspergilloma.aspergillus tracheobronchitis and aspergillus empyema are two rare manifestations of aspergillus infection. this case report presents a patient with chronic obstructive pulmonary disease who developed a pseudomembranous aspergillus tracheobronchitis, bronchopleural fistula and empyema 16 months after lobectomy for an aspergilloma. bronchoscopy proved to be important for assessment of severity. combined systemic anti-fungal treatment (voriconazole) and open window thoracostomy were used to succes ...201425379394
acute respiratory distress caused by neosartorya udagawae.we describe the first reported case of acute respiratory distress syndrome (ards) attributed to neosartorya udagawae infection. this mold grew rapidly in cultures of multiple respiratory specimens from a previously healthy 43-year-old woman. neosartorya spp. are a recently recognized cause of invasive disease in immunocompromised patients that can be mistaken for their sexual teleomorph, aspergillus fumigatus. because the cultures were sterile, phenotypic identification was not possible. dna seq ...201425379388
aspergillus fumigatus and related species.the genus aspergillus contains etiologic agents of aspergillosis. the clinical manifestations of the disease range from allergic reaction to invasive pulmonary infection. among the pathogenic aspergilli, aspergillus fumigatus is most ubiquitous in the environment and is the major cause of the disease, followed by aspergillus flavus, aspergillus niger, aspergillus terreus, aspergillus nidulans, and several species in the section fumigati that morphologically resemble a. fumigatus. patients that a ...201425377144
synthesis of a pentasaccharide and neoglycoconjugates related to fungal α-(1→3)-glucan and their use in the generation of antibodies to trace aspergillus fumigatus cell wall.3-aminopropyl α-(1→3)-pentaglucoside, a fragment of α-(1→3)-glucan of the cell wall of aspergillus fumigatus, has been synthesized in a blockwise approach. the application of mono- and disaccharide n-phenyltrifluoroacetimidates bearing a stereodirecting 6-o-benzoyl group was essential for stereoselective α-glucosylations. in the products, p-methoxyphenyl and levulinoyl groups served as orthogonal protecting groups for the anomeric position and 3-oh group, respectively. their removal from shared ...201525376936
chip-seq and in vivo transcriptome analyses of the aspergillus fumigatus srebp srba reveals a new regulator of the fungal hypoxia response and virulence.the aspergillus fumigatus sterol regulatory element binding protein (srebp) srba belongs to the basic helix-loop-helix (bhlh) family of transcription factors and is crucial for antifungal drug resistance and virulence. the latter phenotype is especially striking, as loss of srba results in complete loss of virulence in murine models of invasive pulmonary aspergillosis (ipa). how fungal srebps mediate fungal virulence is unknown, though it has been suggested that lack of growth in hypoxic conditi ...201425375670
a modified recombineering protocol for the genetic manipulation of gene clusters in aspergillus fumigatus.genomic analyses of fungal genome structure have revealed the presence of physically-linked groups of genes, termed gene clusters, where collective functionality of encoded gene products serves a common biosynthetic purpose. in multiple fungal pathogens of humans and plants gene clusters have been shown to encode pathways for biosynthesis of secondary metabolites including metabolites required for pathogenicity. in the major mould pathogen of humans aspergillus fumigatus, multiple clusters of co ...201425372385
sinobronchial allergic aspergillosis with allergic bronchopulmonary aspergillosis: a less common co-existence.allergic bronchopulmonary aspergillosis (abpa) is an immunological pulmonary disorder that is characterised by a hyper-responsiveness of the airways to aspergillus fumigatus. although several other fungi may also present with similar clinical conditions, aspergillus remains the most common fungal pathogen causing airway infections. co-existence of abpa with allergic aspergillus sinusitis (aas) is an uncommon presentation. the concept of one airway/one disease justifies the co-existence of abpa w ...201425371437
cloning, overexpression, and characterization of a highly active endoinulinase gene from aspergillus fumigatus cl1 for production of inulo-oligosaccharides.in this study, an endoinulinase gene from aspergillus fumigatus was cloned and overexpressed in pichia pastoris. a maximum activity, 3860 u/ml, of the recombinant endoinulinase was obtained by using a high cell-density fermentation approach. the recombinant endoinulinase with a molecular weight of 58 kda was purified for further enzymatic investigation. the ph and temperature optima were ph 6.0 and 55 °c, and the k m and v max values toward inulin were 2.18 mm and 1590 μmol min(-1) mg(-1), respe ...201525369893
multispecific aspergillus t cells selected by cd137 or cd154 induce protective immune responses against the most relevant mold infections.aspergillus and mucorales species cause severe infections in patients after hematopoietic stem cell transplantation (hsct). induction of antifungal cd4(+) t-helper type 1 (th1) immunity is an appealing strategy to combat these infections. immunotherapeutic approaches are so far limited because of a lack of antigens inducing protective t cells, their elaborate production, and the need of targeting a broad spectrum of pathogenic fungi.201525367298
b lymphocytes regulate airway granulocytic inflammation and cytokine production in a murine model of fungal allergic asthma.sensitization to fungi often leads to a severe form of asthma that is particularly difficult to manage clinically, resulting in increased morbidity and hospitalizations in these patients. although b lymphocytes might exacerbate asthma symptoms through the production of ige, these cells might also be important in the protective response against inhaled fungi. through cytokine release and t-cell interactions, these lymphocytes might also influence the development and maintenance of airway wall fib ...201525363529
erratum to: phylogenetic analyses on the diversity of aspergillus fumigatus sensu lato based on five orthologous loci. 201525361842
agent-based model of human alveoli predicts chemotactic signaling by epithelial cells during early aspergillus fumigatus infection.aspergillus fumigatus is one of the most important human fungal pathogens, causing life-threatening diseases. since humans inhale hundreds to thousands of fungal conidia every day, the lower respiratory tract is the primary site of infection. current interaction networks of the innate immune response attribute fungal recognition and detection to alveolar macrophages, which are thought to be the first cells to get in contact with the fungus. at present, these networks are derived from in vitro or ...201425360787
purification and characterization of a mycelial catalase from scedosporium boydii, a useful tool for specific antibody detection in patients with cystic fibrosis.scedosporium boydii is an opportunistic filamentous fungus which may be responsible for a wide variety of infections in immunocompetent and immunocompromised individuals. this fungus belongs to the scedosporium apiospermum species complex, which usually ranks second among the filamentous fungi colonizing the airways of patients with cystic fibrosis (cf) and may lead to allergic bronchopulmonary mycoses, sensitization, or respiratory infections. upon microbial infection, host phagocytic cells rel ...201525355796
erythropoietin combined with liposomal amphotericin b improves outcome during disseminated aspergillosis in mice.disseminated aspergillosis is responsible for a high mortality rate, despite the use of antifungal drugs. adjuvant therapies are urgently needed to improve the outcome. the aim of this study was to demonstrate that the cytoprotective effect of erythropoietin (epo) combined with amphotericin b can reduce the mortality rate in a murine model of disseminated aspergillosis. after infection with aspergillus fumigatus, neutropenic mice were randomized to receive vehicle or 7.5 mg/kg liposomal amphoter ...201425352847
possible mechanism of antifungal phenazine-1-carboxamide from pseudomonas sp. against dimorphic fungi benjaminiella poitrasii and human pathogen candida albicans.investigation of antifungal mechanism of phenazine 1-carboxamide (pc) produced by a pseudomonas strain mcc2142.201525348290
invasive aspergillosis in liver transplant recipients: epidemiology, clinical characteristics, treatment, and outcomes in 116 cases.invasive aspergillosis (ia) in liver transplant recipients is associated with grave outcomes. we reviewed 116 individual cases reported in the literature from 1985 to 2013. ia was diagnosed after a median of 25 days after transplantation and involved a single organ in 51% of the cases, whereas in the remaining cases, multiple sites were involved. the most common infecting aspergillus species were aspergillus fumigatus (73%), aspergillus flavus (14%), and aspergillus terreus (8%). amphotericin b ...201525348192
comparison of toxicogenic and immunosuppressive capacity of aspergillus fumigatus strains isolated from clinical and corn silage samples.to compare clinical and environmental aspergillus fumigatus strains on their toxicogenic and immunosuppressive capacity.201525346380
a breath fungal secondary metabolite signature to diagnose invasive aspergillosis.invasive aspergillosis (ia) remains a leading cause of mortality in immunocompromised patients, in part due to the difficulty of diagnosing this infection.201425342502
a murine inhalation model to characterize pulmonary exposure to dry aspergillus fumigatus conidia.most murine models of fungal exposure are based on the delivery of uncharacterized extracts or liquid conidia suspensions using aspiration or intranasal approaches. studies that model exposure to dry fungal aerosols using whole body inhalation have only recently been described. in this study, we aimed to characterize pulmonary immune responses following repeated inhalation of conidia utilizing an acoustical generator to deliver dry fungal aerosols to mice housed in a nose only exposure chamber. ...201425340353
sequence-based prediction of linear autoepitopes involved in pathogenesis of ipah and the corresponding organism sources of molecular mimicry.we proposed here a sequence-based approach predicting some microorganisms as possible sources of autoantigen-related molecular mimicry concerning idiopathic pulmonary arterial hypertension (ipah) and related hypertension mostly accompanying autoimmune diseases and aids (apah). this approach (species_valence) processes the database occurrences of linear autoepitope-related short dense quasi-pattern sequences (dqpa) generated based on identities of important autoantigenic sequences. the correspond ...201425335565
the ph-responsive pacc transcription factor of aspergillus fumigatus governs epithelial entry and tissue invasion during pulmonary aspergillosis.destruction of the pulmonary epithelium is a major feature of lung diseases caused by the mould pathogen aspergillus fumigatus. although it is widely postulated that tissue invasion is governed by fungal proteases, a. fumigatus mutants lacking individual or multiple enzymes remain fully invasive, suggesting a concomitant requirement for other pathogenic activities during host invasion. in this study we discovered, and exploited, a novel, tissue non-invasive, phenotype in a. fumigatus mutants lac ...201425329394
uncommon opportunistic fungal infections of oral cavity: a review.the majority of opportunistic oral mucosal fungal infections are due to candida albicans and aspergillus fumigatus species. mucor and cryptococcus also have a major role in causing oral infections, whereas geotrichum, fusarium, rhodotorula, saccharomyces and penicillium marneffei are uncommon pathogens in the oral cavity. the broad spectrum of clinical presentation includes pseudo-membranes, abscesses, ulcers, pustules and extensive tissue necrosis involving bone. this review discusses various u ...201425328305
concomitant occurrence of itraconazole-resistant and -susceptible strains of aspergillus fumigatus in routine cultures.resistance to triazoles in aspergillus fumigatus has emerged in several countries and is usually mediated by mutations in the cyp51a gene. we determined the presence of both itraconazole-susceptible and -resistant a. fumigatus in routine cultures isolated from environmental and clinical samples.201525326091
resistance to antifungals that target cyp51.fungal diseases are an increasing global burden. fungi are now recognised to kill more people annually than malaria, whilst in agriculture, fungi threaten crop yields and food security. azole resistance, mediated by several mechanisms including point mutations in the target enzyme (cyp51), is increasing through selection pressure as a result of widespread use of triazole fungicides in agriculture and triazole antifungal drugs in the clinic. mutations similar to those seen in clinical isolates as ...201425320648
th and treg response induced by aspergillus fumigatus pulsed dendritic cells in vitro.dendritic cells (dcs) can recognize the pathogen-associated molecular patterns (pamp) of aspergillus fumigatus (a. fumigatus), activating the immune response. during a. fumigatus infection, a th and treg response induced in the fungi-pulsed dcs is not yet well understood.201425316239
rna-seq reveals the pan-transcriptomic impact of attenuating the gliotoxin self-protection mechanism in aspergillus fumigatus.aspergillus fumigatus produces a number of secondary metabolites, one of which, gliotoxin, has been shown to exhibit anti-fungal activity. thus, a. fumigatus must be able to protect itself against gliotoxin. indeed one of the genes in the gliotoxin biosynthetic gene cluster in a. fumigatus, glit, is required for self-protection against the toxin- however the global self-protection mechanism deployed is unclear. rna-seq was employed to identify genes differentially regulated upon exposure to glio ...201425311525
characterization of the aspergillus fumigatus detoxification systems for reactive nitrogen intermediates and their impact on virulence.aspergillus fumigatus is a saprophytic mold that can cause life-threatening infections in immunocompromised patients. in the lung, inhaled conidia are confronted with immune effector cells that attack the fungus by various mechanisms such as phagocytosis, production of antimicrobial proteins or generation of reactive oxygen intermediates. macrophages and neutrophils can also form nitric oxide (no) and other reactive nitrogen intermediates (rni) that potentially also contribute to killing of the ...201425309516
azole, polyene and echinocandin mic distributions for wild-type, tr34/l98h and tr46/y121f/t289a aspergillus fumigatus isolates in the netherlands.to determine the mic distributions of itraconazole, voriconazole and posaconazole and non-azole drugs for wild-type cyp51a, as well as tr(34)/l98h and tr(46)/y121f/t289a cyp51a mutants of aspergillus fumigatus.201525301884
production and immobilization of enzymes by solid-state fermentation of agroindustrial waste.the recovery of by-products from agri-food industry is currently one of the major challenges of biotechnology. castilla-la mancha produces around three million tons of waste coming from olive oil and wine industries, both of which have a pivotal role in the economy of this region. for this reason, this study reports on the exploitation of grape skins and olive pomaces for the production of lignocellulosic enzymes, which are able to deconstruct the agroindustrial waste and, therefore, reuse them ...201525300855
antimicrobial activity, toxicity and selectivity index of two biflavonoids and a flavone isolated from podocarpus henkelii (podocarpaceae) leaves.different parts of podocarpus henkelii have been used in many cultures around the world to treat ailments such as cholera, stomach diseases, rheumatism, cancer, canine distemper in dogs and gall sickness in cattle. the aim of this study was to evaluate the biological activity and toxicity of isolated compounds from podocarpus henkelii after an earlier study indicated a promising activity in crude extracts against viral pathogens of veterinary importance.201425293523
quantification of c. globosum spores in house dust samples.chaetomium globosum is one of the most common fungi that grows in damp buildings and occurs in agricultural and forestry workplaces. using sera from atopic patients, we characterized and purified an extracellular chitosanase (chg47) from c. globosum that is antigenic to humans. the study reports the production of monoclonal antibodies to the protein. three capture elisas were developed for chg47 for detection of spores and spore and mycelial fragments in dust samples using different mono- and po ...201425292122
whole glucan particles as a vaccine against murine aspergillosis.vaccination with heat-killed saccharomyces cerevisiae (hky) protects against experimental infection by pathogenic fungi of five genera. here we tested whether purified saccharomyces cell wall β-glucan could induce protection against systemic aspergillosis. cd-1 mice were given three weekly vaccine doses subcutaneously prior to intravenous infection with aspergillus fumigatus. mice received pbs, 2.5 mg hky, whole glucan particles (wgp), wgp conjugated to bsa (0.06 to 12 mg per dose), a soluble me ...201425288643
structure of an aspergillus fumigatus old yellow enzyme (easa) involved in ergot alkaloid biosynthesis.the aspergillus fumigatus old yellow enzyme (oye) easa reduces chanoclavine-i aldehyde to dihydrochanoclavine aldehyde and works in conjunction with festuclavine synthase at the branchpoint for ergot alkaloid pathways. the crystal structure of the fmn-loaded easa was determined to 1.8 å resolution. the active-site amino acids of oye are conserved, supporting a similar mechanism for reduction of the α/β-unsaturated aldehyde. the c-terminal tail of one monomer packs into the active site of a monom ...201425286934
luliconazole for the treatment of fungal infections: an evidence-based review.luliconazole is an imidazole antifungal agent with a unique structure, as the imidazole moiety is incorporated into the ketene dithioacetate structure. luliconazole is the r-enantiomer, and has more potent antifungal activity than lanoconazole, which is a racemic mixture. in this review, we summarize the in vitro data, animal studies, and clinical trial data relating to the use of topical luliconazole. preclinical studies have demonstrated excellent activity against dermatophytes. further, in vi ...201425285056
mycological monitoring of selected aquatic ecosystems in the context of epidemiological hazards. drinking water.many species of microfungi are reported in aquatic ecosystems with different frequency. their number constantly fluctuates depending on the concentration of environmental and anthropogenic factors. drinking water, tap and bottled, is essential for the proper functioning of the human body. it is also the main component of food and hence it should be safe for human health and free of contaminants. the mycological purity of tap water in two large cities in the region (olsztyn and ostrołęka) and a s ...201425281816
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