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synthesis, in-vitro antibacterial, antifungal, and molecular modeling of potent anti-microbial agents with a combined pyrazole and thiophene pharmacophore.ethyl 5-acetyl-4-methyl-2-(phenylamino)thiophene-3-carboxylate (2) and there derivatives 3a-c, 4, 6a-c and 9a-f were synthesized. the structure of compound 2 was deduced by 1h-nmr, 13c-nmr, ft-ir, ms, microanalysis, and single-crystal x-ray crystallography. the compound crystallized in the monoclinic system, with space group p21/c and cell coordinates a = 8.5752(16) å, b = 21.046(4) å, c = 8.2941(12) å, β = 101.131(6)°, v = 1468.7(4) å3, and z = 4. compounds 2, 3a-c, 4, 5a-c and 9a-f were subjec ...201526007175
case of seropositive allergic bronchopulmonary aspergillosis in a 10-year-old girl without previously documented asthma.allergic bronchopulmonary aspergillosis (abpa) is a hypersensitivity lung disease due to bronchial colonization of aspergillus fumigatus that occurs in susceptible patients with asthma or cystic fibrosis. a 10-year-old girl was referred to the department of pediatric pulmonology for persistent consolidations on chest radiography. pulmonary consolidations were observed in the right upper and left lower lobes and were not resolved with a 4-week prescription of broad-spectrum antibiotics. the patie ...201526124850
evolution of the immune response to chronic airway colonization with aspergillus fumigatus hyphae.airway colonization by the mold aspergillus fumigatus is common in patients with underlying lung disease and is associated with chronic airway inflammation. studies probing the inflammatory response to colonization with a. fumigatus hyphae have been hampered by the lack of a model of chronic colonization in immunocompetent mice. by infecting mice intratracheally with conidia embedded in agar beads (af beads), we have established an in vivo model to study the natural history of airway colonizatio ...201526123803
proteomic analyses reveal the key roles of brla and abaa in biogenesis of gliotoxin in aspergillus fumigatus.the opportunistic human pathogenic fungus aspergillus fumigatus primarily reproduces by forming a large number of asexual spores (conidia). sequential activation of the central regulators brla, abaa and weta is necessary for the fungus to undergo asexual development. in this study, to address the presumed roles of these key developmental regulators during proliferation of the fungus, we analyzed and compared the proteomes of vegetative cells of wild type (wt) and individual mutant strains. appro ...201526032501
a facile synthesis of novel miconazole analogues and the evaluation of their antifungal activity.four novel miconazole analogues (8-11) were synthetized and evaluated for activity against four filamentous fungi (mucor hiemalis, aspergillus fumigatus, trichosporon cutaneum, and rhizopus oryzae) and eight species of candida as yeast specimens. compounds 9 and 10 showed very good activity when evaluated in yeast (mic 0.112 and 0.163 μg/ml) compared to the reference compound, itraconazole (mic 0.067 μg/ml). the best antifungal activity in filamentous strains was shown by compound 9. hence compo ...201525989345
prospective multicenter international surveillance of azole resistance in aspergillus fumigatus.to investigate azole resistance in clinical aspergillus isolates, we conducted prospective multicenter international surveillance. a total of 3,788 aspergillus isolates were screened in 22 centers from 19 countries. azole-resistant a. fumigatus was more frequently found (3.2% prevalence) than previously acknowledged, causing resistant invasive and noninvasive aspergillosis and severely compromising clinical use of azoles.201525988348
nationwide surveillance of azole resistance in aspergillus diseases.aspergillus disease affects a broad patient population, from patients with asthma to immunocompromised patients. azole resistance has been increasingly reported in both clinical and environmental aspergillus strains. the prevalence and clinical impact of azole resistance in different patient populations are currently unclear. this 1-year prospective multicenter cohort study aimed to provide detailed epidemiological data on aspergillus resistance among patients with aspergillus disease in belgium ...201525987612
cyp2c19*17 genetic polymorphism--an uncommon cause of voriconazole treatment failure.we describe an immunosuppressed, 48-year-old male, allogeneic hematopoietic stem cell transplant recipient with severe graft-versus-host disease who developed invasive pulmonary aspergillus fumigatus infection 6 months after transplant. his lack of response to voriconazole and undetectable serum trough levels of the drug led us to establish that he had the uncommon cytochrome p450, cyp2c19*17 allele, which leads to a rapid metabolism of voriconazole but not of the other azole antifungals. we dis ...201525986028
cytokines induce effector t-helper cells during invasive aspergillosis; what we have learned about t-helper cells?invasive aspergillosis caused by aspergillus species (aspergillus fumigatus, a. flavus, and a. terreus) is life-threatening infections in immunocompromised patients. understanding the innate and adaptive immune response particularly t-helper cells (th-cells) against these aspergillus species and how the different sub-set of th-cells are regulated by differentiating cytokines at primary target organ site like lung, kidney and brain is of great significance to human health. this review focuses on ...201526029179
characterization and identification of the xylanolytic enzymes from aspergillus fumigatus z5.plant biomass, the most abundant natural material on earth, represents a vast source of food and energy in nature. as the main component of plant biomass, xylan is a complex polysaccharide comprising a linear β(1,4)-linked backbone of xylosyl residues substituted by acetyl, arabinosyl, glucuronysyl and 4-o-methylglucuronycyl residues.201526100973
transcription factor ads-4 regulates adaptive responses and resistance to antifungal azole stress.azoles are commonly used as antifungal drugs or pesticides to control fungal infections in medicine and agriculture. fungi adapt to azole stress by rapidly activating the transcription of a number of genes, and transcriptional increases in some azole-responsive genes can elevate azole resistance. the regulatory mechanisms that control transcriptional responses to azole stress in filamentous fungi are not well understood. this study identified a bzip transcription factor, ads-4 (antifungal drug s ...201526100701
data for itraq secretomic analysis of aspergillus fumigatus in response to different carbon sources.here, we provide data related to the research article entitled "quantitative proteomics study of aspergillus fumigatus secretome revealed deamidation of secretory enzymes" by adav et al. (j. proteomics (2015) [1]). aspergillus sp. plays an important role in lignocellulosic biomass recycling. to explore biomass hydrolyzing enzymes of a. fumigatus, we profiled secretome under different carbon sources such as glucose, cellulose, xylan and starch by high throughput quantitative proteomics using isob ...201526217740
rubicon swaps autophagy for lap.phagocytic cells engulf their prey into vesicular structures called phagosomes, of which a certain proportion becomes demarcated for enhanced maturation by a process called lc3-associated phagocytosis (lap). light has now been shed on the molecular requirements of lap, establishing a central role for the protein rubicon in the immune response to aspergillus fumigatus.201526123110
update on antifungal drug resistance.invasive fungal infections remain a major source of global morbidity and mortality, especially among patients with underlying immune suppression. successful patient management requires antifungal therapy. yet, treatment choices are restricted due to limited classes of antifungal agents and the emergence of antifungal drug resistance. in some settings, the evolution of multidrug-resistant strains insensitive to several classes of antifungal agents is a major concern. the resistance mechanisms res ...201526120512
molecular-based allergy diagnosis of allergic bronchopulmonary aspergillosis in aspergillus fumigatus-sensitized japanese patients.distinguishing between patients with allergic bronchopulmonary aspergillosis (abpa) and aspergillus fumigatus (af)-sensitized asthmatic patients without abpa is sometimes difficult owing to the ige-cross-reactivity between af and other fungal allergens.201526118958
functional analysis of sterol transporter orthologues in the filamentous fungus aspergillus nidulans.polarized growth in filamentous fungi needs a continuous supply of proteins and lipids to the growing hyphal tip. one of the important membrane compounds in fungi is ergosterol. at the apical plasma membrane ergosterol accumulations, which are called sterol-rich plasma membrane domains (srds). the exact roles and formation mechanism of the srds remained unclear, although the importance has been recognized for hyphal growth. transport of ergosterol to hyphal tips is thought to be important for th ...201526116213
high diversity of non-sporulating moulds in respiratory specimens of immunocompromised patients: should all the species be reported when diagnosing invasive aspergillosis?non-sporulating moulds (nsms) isolated from respiratory specimens are usually discarded without further testing although they may have pathogenic effects in immunocompromised patients. the objective of this study was to determine the identity and frequency of nsms in patients with haematological malignancies. we analysed the mycological results of 251 consecutive respiratory samples from 104 haematology patients. yeast and sporulating moulds were identified at the genus/species level according t ...201526214496
azole-resistant aspergillus fumigatus isolates carrying tr₃₄/l98h mutations in taiwan.cumulative evidence described the emergence and geographical expansion of azole-resistant a. fumigatus associated with azole treatment failure. to investigate the status of azole resistance in a. fumigatus in taiwan, we studied 38 a. fumigatus clinical isolates cultivated from 31 patients at two teaching hospitals from 2011 to 2014. three isolates obtained from respiratory samples of two azole-naïve patients with pulmonary aspergillosis were found to display multi-azole resistance and cross resi ...201526214171
aspergillus fumigatus spinal abscess in an immunocompetent child. 201526208570
isolated enteric aspergillosis in a non severely immunocompromised patient. case report and literature review.invasive aspergillosis is a life-threatening, opportunistic fungal infection that mainly affects immunocompromised patients, particularly those receiving immunosuppressive therapy or high-dose corticosteroids. the most common portal of entry in aspergillosis is the lung, so the isolated occurrence of intestinal aspergillosis in the absence of pulmonary disease is an unusual pattern.201526206431
analysis of the aspergillus fumigatus biofilm extracellular matrix by solid-state nuclear magnetic resonance spectroscopy.aspergillus fumigatus is commonly responsible for lethal fungal infections among immunosuppressed individuals. a. fumigatus forms biofilm communities that are of increasing biomedical interest due to the association of biofilms with chronic infections and their increased resistance to antifungal agents and host immune factors. understanding the composition of microbial biofilms and the extracellular matrix is important to understanding function and, ultimately, to developing strategies to inhibi ...201526163318
aspergillus fumigatus enhances elastase production in pseudomonas aeruginosa co-cultures.in the cystic fibrosis (cf) lung the presence of bacteria and fungi in the airways promotes an inflammatory response causing progressive lung damage, ultimately leading to high rates of morbidity and mortality. we hypothesized that polymicrobial interactions play an important role in promoting airway pathogenesis. we therefore examined the interplay between the most commonly isolated bacterial cf pathogen, pseudomonas aeruginosa, and the most prevalent filamentous fungi, aspergillus fumigatus, t ...201526162475
[invasive aspergillosis sinusitis in a diabetic]. 201526161202
drug-drug interaction between isavuconazole and tacrolimus: a case report indicating the need for tacrolimus drug-level monitoring.despite the known significant drug-drug interaction between isavuconazole and tacrolimus, there are no recommendations on dose adjustment when these drugs are given concomitantly. we report on a patient with a mediastinal aspergillus fumigatus infection resistant to posaconazole and describe how she was successfully managed with tacrolimus therapeutic drug-level monitoring.201526248976
invasive fungal sinusitis involving the orbital apex in a patient with chronic renal failure.an 82-year-old man with chronic renal failure presented with invasive fungal sinusitis involving the right orbital apex. intravenous liposomal amphotericin b was immediately administered with an intravenous sodium supplement. subsequently, endoscopic sinus surgery was performed. aspergillus fumigatus was detected in nasal discharge culture on day 12. because the patient's renal function had deteriorated by this time, therapy was changed to nasal inhalation of amphotericin b, which was discontinu ...201527928353
interplay between gliotoxin resistance, secretion, and the methyl/methionine cycle in aspergillus fumigatus.mechanistic studies on gliotoxin biosynthesis and self-protection in aspergillus fumigatus, both of which require the gliotoxin oxidoreductase glit, have revealed a rich landscape of highly novel biochemistries, yet key aspects of this complex molecular architecture remain obscure. here we show that an a. fumigatus δglia strain is completely deficient in gliotoxin secretion but still retains the ability to efflux bisdethiobis(methylthio)gliotoxin (bmgt). this correlates with a significant increa ...201526150413
a novel mycovirus from aspergillus fumigatus contains four unique dsrnas as its genome and is infectious as dsrna.we report the discovery and characterization of a double-stranded rna (dsrna) mycovirus isolated from the human pathogenic fungus aspergillus fumigatus, aspergillus fumigatus tetramycovirus-1 (afutmv-1), which reveals several unique features not found previously in positive-strand rna viruses, including the fact that it represents the first dsrna (to our knowledge) that is not only infectious as a purified entity but also as a naked dsrna. the afutmv-1 genome consists of four capped dsrnas, the ...201526139522
recombination detection in aspergillus fumigatus through single nucleotide polymorphisms typing.the first evidence of sexual reproduction in aspergillus fumigatus was reported in 2009. nevertheless, it remains difficult to understand how a. fumigatus is able to reproduce through this mode in its natural environment and how frequently this occurs. the aim of this study was to analyse single nucleotide polymorphisms (snps) in a set of environmental and clinical isolates of a. fumigatus to detect signatures of recombination. a group of closely related portuguese a. fumigatus isolates was char ...201526189756
clinical-scale isolation of the total aspergillus fumigatus-reactive t-helper cell repertoire for adoptive transfer.evidence of the criticality of the adaptive immune response for controlling invasive aspergillosis has been provided. this observation is supported by the fact that invasive aspergillosis, a grave complication of allogeneic stem cell transplantation, occurs long after myeloid reconstitution in patients with low t-cell engraftment and/or on immunosuppressants. adoptive t-cell transfer might be beneficial, but idiosyncrasies of aspergillus fumigatus and the anti-aspergillus immune response render ...201526188965
t helper 2 response in allergic bronchopulmonary aspergillosis is not driven by specific aspergillus antigens.allergic bronchopulmonary aspergillosis (abpa) is characterized by an allergic immunological response to aspergillus fumigatus. in this study, we investigated whether certain aspergillus antigens are more allergenic than others, as was postulated previously. we stimulated peripheral blood mononuclear cells from patients with abpa with the classically described a. fumigatus allergens aspf1, aspf2, aspf3, and aspf4, as well as two other aspergillus antigens, crf1 and catalase1. activated cd4+ t ce ...201526179335
[retraction. allergic bronchopulmonary aspergillosis in refractory asthma: about a case report]. 201526175839
erratum for abdolrasouli et al., genomic context of azole resistance mutations in aspergillus fumigatus determined using whole-genome sequencing. 201526173700
an alternative host model of a mixed fungal infection by azole susceptible and resistant aspergillus spp strains.aspergillus fumigatus is the most common mold involved in human infections. however, the number of non-fumigatus species able to cause disease is continuously increasing. among them, aspergillus lentulus is reported in hematological and cystic fibrosis patients and in those treated with corticosteroids. a. lentulus differs from a. fumigatus in some clinically relevant aspects such as virulence and antifungal susceptibility, showing high mics to most antifungals. previous studies proved that a. l ...201526065322
a pharmacokinetic/pharmacodynamic analysis of a standard voriconazole regimen in different cyp2c19 genotypes by monte carlo simulation.the objective of this study was to evaluate the standard voriconazole dosage regimen (maintenance dose was 200 mg bid orally) against aspergillus infections in different cyp2c19 genotypes from a pharmacokinetic/pharmacodynamic (pk/pd) perspective.201526062298
caspofungin treatment of aspergillus fumigatus results in chsg-dependent upregulation of chitin synthesis and the formation of chitin-rich microcolonies.treatment of aspergillus fumigatus with echinocandins such as caspofungin inhibits the synthesis of cell wall β-1,3-glucan, which triggers a compensatory stimulation of chitin synthesis. activation of chitin synthesis can occur in response to sub-mics of caspofungin and to cacl2 and calcofluor white (cfw), agonists of the protein kinase c (pkc), and ca(2+)-calcineurin signaling pathways. a. fumigatus mutants with the chs gene (encoding chitin synthase) deleted (δafchs) were tested for their resp ...201526169407
probiotic potential of lactobacillus strains with antifungal activity isolated from animal manure.the aim of the study was to isolate and characterize the lactic acid bacteria (lab) from animal manure. among the thirty lab strains, four strains, namely, kcc-25, kcc-26, kcc-27, and kcc-28, showed good cell growth and antifungal activity and were selected for further characterization. biochemical and physiology properties of strains confirmed that the strains are related to the lactobacillus sp.; further, the 16s rrna sequencing confirmed 99.99% sequence similarity towards lactobacillus planta ...201526167534
synthesis, in vitro and in silico studies of some novel 5-nitrofuran-2-yl hydrazones as antimicrobial and antitubercular agents.in this study, we synthesized two series of novel 5-nitrofuran-2-carbohydrazides 21a-h and 22a-e in addition to a third series of thiophene-2-carbohydrazides 23a-g to develop potent antimicrobial and/or antitubercular agents. the newly synthesized compounds were evaluated in vitro for their antimicrobial and antimycobacterial activities. most of the 5-nitrofuran-2-carbohydrazides 21a-h and 22a-e displayed variable activity against aspergillus fumigates, staphylococcus aureus, streptococcus pneum ...201526155871
phytase production through response surface methodology and molecular characterization of aspergillus fumigatus nf191.phytase play an important role in phytic acid catalysis that act as a food inhibitor in cereals. here, we isolated high phytase producing isolates nf191 closely related to aspergillus fumigatus sp. from piggery soil. dna was isolated from the fungal culture and amplified the its region using its1 and its4 primer using pcr. the 400-900 bp amplicon was gel eluted and subjected to sequencing. the sequencing results were assembled and compared with ncbi data base which showed the 99% identity of asp ...201526155674
the aspergillus fumigatus septins play pleiotropic roles in septation, conidiation, and cell wall stress, but are dispensable for virulence.septins are a conserved family of gtpases that regulate important cellular processes such as cell wall integrity, and septation in fungi. the requirement of septins for virulence has been demonstrated in the human pathogenic yeasts candida albicans and cryptococcus neoformans, as well as the plant pathogen magnaporthe oryzae. aspergillus spp. contains five genes encoding for septins (aspa-e). while the importance of septins aspa, aspb, aspc, and aspe for growth and conidiation has been elucidate ...201526051489
first determination of azole resistance in aspergillus fumigatus strains carrying the tr34/l98h mutations in turkey.aspergillus fumigatus is the most important etiological agent of invasive aspergillosis. recently, an increasing number of azole-resistant a. fumigatus isolates have been described in various countries. the prevalence of azole resistance was investigated in this study using our culture collection of a. fumigatus isolates collected between 1999 and 2012 from clinical specimens. seven hundred and forty-six a. fumigatus isolates, collected from 419 patients, were investigated. first, all isolates w ...201526048062
the role of lox-1 in innate immunity to aspergillus fumigatus in corneal epithelial cells.to determine the role of lectin-like oxidized low-density lipoprotein receptor 1 (lox-1) in corneal epithelial cells exposed to fungus.201526047046
metabolites produced by the endophytic fungus aspergillus fumigatus from the stem of erythrophloeum fordii oliv.a new diketopiperazine alkaloid named spirotryprostatin k (1), and five known alkaloids, spiro[5h,10h-dipyrrolo[1,2-a:1',2'-d]pyrazine-2(3h),2'-[2h]-indole]-3',5,10(1'h) trione (2), 6-methoxyspirotryprostatin b (3), pseurotin a (4), n-β-acetyltryptamine (5), and lumichrome (6) were isolated from the endophytic fungus aspergillus fumigatus. the structure and the absolute configuration of spirotryprostatin k were established by extensive spectroscopic analyses, acid hydrolysis and ecd calculations ...201526111169
automated quantification of the phagocytosis of aspergillus fumigatus conidia by a novel image analysis algorithm.studying the pathobiology of the fungus aspergillus fumigatus has gained a lot of attention in recent years. this is due to the fact that this fungus is a human pathogen that can cause severe diseases, like invasive pulmonary aspergillosis in immunocompromised patients. because alveolar macrophages belong to the first line of defense against the fungus, here, we conduct an image-based study on the host-pathogen interaction between murine alveolar macrophages and a. fumigatus. this is achieved by ...201526106370
lysophospholipids from the guangxi sponge spirastrella purpurea.four known (1-4) and two new (5 and 6) lysophospholipids were isolated from the sponge spirastrella purpurea from weizhou island, guangxi autonomous region, china. the structures of the new compounds (5 and 6) were elucidated by detailed spectroscopic techniques, including 1d and 2d nmr ((1)h and (13)c nmr, (1)h-(1)h cosy, hsqc, and hmbc) as well as mass spectrometry and optical rotation experiments. the known compounds (1-4) were identified by comparison of their spectroscopic data and specific ...201526037518
genomic context of azole resistance mutations in aspergillus fumigatus determined using whole-genome sequencing.a rapid and global emergence of azole resistance has been observed in the pathogenic fungus aspergillus fumigatus over the past decade. the dominant resistance mechanism appears to be of environmental origin and involves mutations in the cyp51a gene, which encodes a protein targeted by triazole antifungal drugs. whole-genome sequencing (wgs) was performed for high-resolution single-nucleotide polymorphism (snp) analysis of 24 a. fumigatus isolates, including azole-resistant and susceptible clini ...201526037120
the role of syk signaling in antifungal innate immunity of human corneal epithelial cells.fungal keratitis is a kind of intractable and sight-threatening diseases. spleen-tyrosine kinase (syk) is a non-receptor tyrosine kinase, which plays an important role in the signaling pathway of the receptors. in the current study, we investigate the expression and function of syk in human corneal epithelial cells with aspergillus fumigatus (a. fumigatus) infection.201526036769
generation of broad-spectrum antifungal drug candidates from the natural product compound aureobasidin a.the natural product aureobasidin a (aba) is a potent, well-tolerated antifungal agent with robust efficacy in animals. although native aba is active against a number of fungi, it has little activity against aspergillus fumigatus, an important human pathogen, and attempts to improve the activity against this organism by structural modifications have to date involved chemistries too complex for continued development. this report describes novel chemistry for the modification of aba. the key step i ...201526101567
analytical comparison of in vitro-spiked human serum and plasma for pcr-based detection of aspergillus fumigatus dna: a study by the european aspergillus pcr initiative.the use of serum or plasma for aspergillus pcr testing facilitates automated and standardized technology. recommendations for serum testing are available, and while serum and plasma are regularly considered interchangeable for use in fungal diagnostics, differences in galactomannan enzyme immunoassay (gm-eia) performance have been reported and are attributed to clot formation. therefore, it is important to assess plasma pcr testing to determine if previous recommendations for serum are applicabl ...201526085614
first detection of aspergillus fumigatus azole-resistant strain due to cyp51a tr46/y121f/t289a in an azole-naive patient in spain.we report the first isolation of a voriconazole-resistant aspergillus fumigatus strain harbouring the azole resistance mechanism tr46/y121f/t289a, recovered from an azole-naive patient in spain with chronic obstructive pulmonary disease. this new finding in spain suggests the spread of this resistance mechanism and reinforces the need for antifungal susceptibility surveillance.201526082842
genome-wide transcriptomic analysis of a superior biomass-degrading strain of a. fumigatus revealed active lignocellulose-degrading genes.various saprotrophic microorganisms, especially filamentous fungi, can efficiently degrade lignocellulose that is one of the most abundant natural materials on earth. it consists of complex carbohydrates and aromatic polymers found in the plant cell wall and thus in plant debris. aspergillus fumigatus z5 was isolated from compost heaps and showed highly efficient plant biomass-degradation capability.201526076650
combining standard clinical methods with pcr showed improved diagnosis of invasive pulmonary aspergillosis in patients with hematological malignancies and prolonged neutropenia.we assessed the diagnostic value of standard clinical methods and combined biomarker testing (galactomannan assay and polymerase chain reaction screening) in a prospective case-control study to detect invasive pulmonary aspergillosis in patients with hematological malignancies and prolonged neutropenia.201526126706
correction: the ph-responsive pacc transcription factor of aspergillus fumigatus governs epithelial entry and tissue invasion during pulmonary aspergillosis. 201526086393
fungus induces the release of il-8 in human corneal epithelial cells, via dectin-1-mediated protein kinase c pathways.to identify whether aspergillus fumigatus (a. fumigatus) hyphae antigens induced the release of interleukin-8 (il-8) in anti-fungal innate immunity of cultured human corneal epithelial cells (hcecs) and determine the involvement of intracellular signalling pathways.201526085988
mitochondrial dynamics in the pathogenic mold aspergillus fumigatus: therapeutic and evolutionary implications.mitochondria within eukaryotic cells continuously fuse and divide. this phenomenon is called mitochondrial dynamics and crucial for mitochondrial function and integrity. we performed a comprehensive analysis of mitochondrial dynamics in the pathogenic mold aspergillus fumigatus. phenotypic characterization of respective mutants revealed the general essentiality of mitochondrial fusion for mitochondrial genome maintenance and the mold's viability. surprisingly, it turned out that the mitochondria ...201526272083
evaluation of the double agar gel immunodiffusion test and of the enzyme-linked immunosorbent assay in the diagnosis and follow-up of patients with chronic pulmonary aspergillosis.the diagnosis of chronic pulmonary aspergillosis (cpa) depends on the radiologic image and the identification of specific antibodies. the present study aimed to evaluate accuracy parameters of enzyme-linked immunosorbent assay (elisa) and of the determination of serum galactomannan level in the diagnosis of patients with cpa, comparing these results with the double agar gel immunodiffusion (did) test. in addition, the prevalence of cross-reactivity and the serological progression after treatment ...201526271000
structure-functional characterization of cytochrome p450 sterol 14α-demethylase (cyp51b) from aspergillus fumigatus and molecular basis for the development of antifungal drugs.aspergillus fumigatus is the opportunistic fungal pathogen that predominantly affects the immunocompromised population and causes 600,000 deaths/year. the cytochrome p450 51 (cyp51) inhibitor voriconazole is currently the drug of choice, yet the treatment efficiency remains low, calling for rational development of more efficient agents. a. fumigatus has two cyp51 genes, cyp51a and cyp51b, which share 59% amino acid sequence identity. cyp51b is expressed constitutively, whereas gene cyp51a is rep ...201526269599
absence of fungal spore internalization by bronchial epithelium in mouse models evidenced by a new bioimaging approach and transmission electronic microscopy.clinical data and experimental studies suggest that bronchial epithelium could serve as a portal of entry for invasive fungal infections. we therefore analyzed the interactions between molds and the bronchial/bronchiolar epithelium at the early steps after inhalation. we developed invasive aspergillosis (aspergillus fumigatus) and mucormycosis (lichtheimia corymbifera) murine models that mimic the main clinical risk factors for these infections. histopathology studies were completed with a speci ...201526165863
high prevalence of azole resistance in aspergillus fumigatus isolates from high-risk patients.aspergillus fumigatus is the leading cause of invasive aspergillosis. adequate treatment is complicated by an increase in azole resistance. here, the incidence of voriconazole, posaconazole and itraconazole resistance in clinical isolates from high-risk patients from either the haematology ward or the icu of the university medical center utrecht in the period 2011-13 is analysed. putative clonality of resistant strains was tested through cyp51a and microsatellite typing.201526163402
evidence for the involvement of cofilin in aspergillus fumigatus internalization into type ii alveolar epithelial cells.the internalization of aspergillus fumigatus into alveolar epithelial cells (aecs) is tightly controlled by host cellular actin dynamics, which require close modulation of the adf (actin depolymerizing factor)/cofilin family. however, the role of cofilin in a. fumigatus internalization into aecs remains unclear.201526268695
production of short-chain fatty acids from the biodegradation of wheat straw lignin by aspergillus fumigatus.the wheat straw lignin-rich fraction (wslig-rf) can be used as a raw material for the production of metabolites for industrial use if ligninolytic mitosporic fungi are used for its biodegradation into aromatics and short-chain fatty acids (scfas, i.e., scfa2-6). although methods for the production of scfa2-6 have been described previously, quantitative data of scfa2-6 production have not been reported. the objectives of this study were to investigate the biodegradation of different concentration ...201526263005
aspergillus in endodontic infection near the maxillary sinus.diseases of the maxillary sinus have been associated with dental roots near the maxillary sinus that have undergone endodontic treatment.201526254203
inhibition of aspergillus fumigatus and its biofilm by pseudomonas aeruginosa is dependent on the source, phenotype and growth conditions of the bacterium.aspergillus fumigatus (af) and pseudomonas aeruginosa (pa) are leading fungal and bacterial pathogens, respectively, in many clinical situations. relevant to this, their interface and co-existence has been studied. in some experiments in vitro, pa products have been defined that are inhibitory to af. in some clinical situations, both can be biofilm producers, and biofilm could alter their physiology and affect their interaction. that may be most relevant to airways in cystic fibrosis (cf), where ...201526252384
draft genome sequence of the pathogenic filamentous fungus aspergillus udagawae strain ifm 46973t.the incidence of aspergillosis by aspergillus infection has dramatically increased in recent years. aspergillus udagawae, a species related to aspergillus fumigatus, is known as an emerging pathogen of aspergillosis. here, we present the draft genome sequence of a. udagawae strain ifm 46973(t).201526251487
a case of late implantable cardiac device infection with aspergillus in an immunocompetent host.with the increasing use of cardiac implantable electronic devices (cied), there has been an associated increase in rate of complications. infection accounts for about 1% of these, of which only a handful were reported secondary to aspergillus fumigatus. all of these were seen in chronically-ill patients with several co-morbid conditions within a few years of implantation. none have been reported in an otherwise immunocompetent patient at 7 years after cied implantation.201526250569
allergic bronchopulmonary aspergillosis in an adult with kartagener syndrome.allergic bronchopulmonary aspergillosis (abpa) is a pulmonary disorder resulting from immune responses directed against inhaled aspergillus fumigatus antigens. it manifests with poorly controlled asthma, fleeting pulmonary opacities and structural lung damage in the form of bronchiectasis. initially defined in individuals suffering from bronchial asthma and cystic fibrosis, it has also been described in patients with other structural lung disorders such as chronic obstructive pulmonary disease, ...201526250371
h-ficolin binds aspergillus fumigatus leading to activation of the lectin complement pathway and modulation of lung epithelial immune responses.aspergillus fumigatus is an opportunistic fungal pathogen that typically infects the lungs of immunocompromised patients leading to a high mortality. h-ficolin, an innate immune opsonin, is produced by type ii alveolar epithelial cells and could participate in lung defences against infections. here, we used the human type ii alveolar epithelial cell line, a549, to determine the involvement of h-ficolin in fungal defence. additionally, we investigated the presence of h-ficolin in bronchoalveolar ...201526133042
in vitro antifungal activity of some traditional persian medicinal plants on pathogenic fungi.to investigate the antifungal activities of the extracts and sub-fractions of phlomis olivieri, verbascum speciosum, sambucus ebulus and erigeron hyrcanicus, four persian medicinal plants used in iranian folk medicine.201526129901
characterization and genetic variability of feed-borne and clinical animal/human aspergillus fumigatus strains using molecular markers.aspergillus fumigatus, the major etiological agent of human and animal aspergillosis, is a toxigenic fungus largely regarded as a single species by macroscopic and microscopic features. however, molecular studies have demonstrated that several morphologically identified a. fumigatus strains might be genetically distinct. this work was aimed to apply pcr-restriction length fragment polymorphisms (pcr-rflp) and random amplification of polymorphic dna (rapd) molecular markers to characterize a set ...201526129892
effects of iron chelators on the formation and development of aspergillus fumigatus biofilm.iron acquisition is crucial for the growth of aspergillus fumigatus. a. fumigatus biofilm formation occurs in vitro and in vivo and is associated with physiological changes. in this study, we assessed the effects of fe chelators on biofilm formation and development. deferiprone (dfp), deferasirox (dfs), and deferoxamine (dfm) were tested for mic against a reference isolate via a broth macrodilution method. the metabolic effects (assessed by xtt [2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2h-tetraz ...201526239975
rnaseq analysis of aspergillus fumigatus in blood reveals a just wait and see resting stage behavior.invasive aspergillosis is started after germination of aspergillus fumigatus conidia that are inhaled by susceptible individuals. fungal hyphae can grow in the lung through the epithelial tissue and disseminate hematogenously to invade into other organs. low fungaemia indicates that fungal elements do not reside in the bloodstream for long.201526311470
design, synthesis, and structure-activity relationship studies of novel thienopyrrolidone derivatives with strong antifungal activity against aspergillus fumigates.in order to further enhance the anti-aspergillus efficacy of our previously discovered antifungal lead compounds (i), two series of novel azoles featuring thieno[2,3-c]pyrrolidone and thieno[3,2-c]pyrrolidone nuclei were designed and evaluated for their in vitro activity on the basis of the binding mode of albaconazole using molecular docking, along with sars of antifungal triazoles. most of target compounds exhibited excellent activity against candida and cryptococcus spp., with mic values in t ...201526310892
[allergic bronchopulmonary aspergillosis: a report of four cases with literature review].to understand the clinical characteristics of allergic bronchopulmonary aspergillosis (abpa) so as to diagnose and treat the disease earlier.201526310647
dectin-1 agonist curdlan modulates innate immunity to aspergillus fumigatus in human corneal epithelial cells.to explore the immunomodulatory effects of curdlan on innate immune responses against aspergillus fumigatus (a. fumigatus) in cultured human corneal epithelial cells (hcecs), and whether c-type lectin receptor dectin-1 mediates the immunomodulatory effects of curdlan.201526309863
nanoscale biophysical properties of the cell surface galactosaminogalactan from the fungal pathogen aspergillus fumigatus.many fungal pathogens produce cell surface polysaccharides that play essential roles in host-pathogen interactions. in aspergillus fumigatus, the newly discovered polysaccharide galactosaminogalactan (gag) mediates adherence to a variety of substrates through molecular mechanisms that are poorly understood. here we use atomic force microscopy to unravel the localization and adhesion of gag on living fungal cells. using single-molecule imaging with tips bearing anti-gag antibodies, we found that ...201526308550
characterization of an n-acetylglucosaminyltransferase involved in aspergillus fumigatus zwitterionic glycoinositolphosphoceramide biosynthesis.glycoinositolphosphoceramides (gipcs) are complex sphingolipids present at the plasma membrane of various eukaryotes with the important exception of mammals. in fungi, these glycosphingolipids commonly contain an α-mannose residue (man) linked at position 2 of the inositol. however, several pathogenic fungi additionally synthesize zwitterionic gipcs carrying an α-glucosamine residue (glcn) at this position. in the human pathogen aspergillus fumigatus, the glcnα1,2ipc core (where ipc is inositolp ...201526306635
soluble collectin-12 (cl-12) is a pattern recognition molecule initiating complement activation via the alternative pathway.soluble defense collagens including the collectins play important roles in innate immunity. recently, a new member of the collectin family named collectin-12 (cl-12 or cl-p1) has been identified. cl-12 is highly expressed in umbilical cord vascular endothelial cells as a transmembrane receptor and may recognize certain bacteria and fungi, leading to opsonophagocytosis. however, based on its structural and functional similarities with soluble collectins, we hypothesized the existence of a fluid-p ...201526290605
genesis of azole antifungal resistance from agriculture to clinical settings.azole fungal resistance is becoming a major public health problem in medicine in recent years. however, it was known in agriculture since several decades; the extensive use of these compounds results in contamination of air, plants, and soil. the increasing frequency of life-threatening fungal infections and the increase of prophylactical use of azoles in high-risk patients, taken together with the evolutionary biology evidence that drug selection pressure is an important factor for the emergenc ...201526289797
hypoxia-inducible factor 1α modulates metabolic activity and cytokine release in anti-aspergillus fumigatus immune responses initiated by human dendritic cells.the mold aspergillus fumigatus causes life-threatening infections in immunocompromised patients. over the past decade, new findings in research have improved our understanding of a. fumigatus-host interactions, including the recent identification of myeloid-expressed hypoxia-inducible factor 1α (hif-1α) as a relevant immune-modulating transcription factor and potential therapeutic target in anti-fungal defense. however, the function of hif-1α signaling for human anti-a. fumigatus immunity is sti ...201526387061
contribution to catalysis of ornithine binding residues in ornithine n5-monooxygenase.the sida ornithine n5-monooxygenase from aspergillus fumigatus is a flavin monooxygenase that catalyzes the nadph-dependent hydroxylation of ornithine. herein we report a mutagenesis study targeting four residues that contact ornithine in crystal structures of sida: lys107, asn293, asn323, and ser469. mutation of lys107 to ala abolishes activity as measured in steady-state oxygen consumption and ornithine hydroxylation assays, indicating that the ionic interaction of lys107 with the carboxylate ...201526375201
identification of the antiphagocytic trypacidin gene cluster in the human-pathogenic fungus aspergillus fumigatus.the opportunistic human pathogen aspergillus fumigatus produces numerous different natural products. the genetic basis for the biosynthesis of a number of known metabolites has remained unknown. the gene cluster encoding for the biosynthesis of the conidia-bound metabolite trypacidin is of particular interest because of its antiprotozoal activity and possible role in the infection process. here, we show that the genes encoding the biosynthesis enzymes of trypacidin reside within an orphan gene c ...201526278536
network modeling reveals cross talk of map kinases during adaptation to caspofungin stress in aspergillus fumigatus.mitogen activated protein kinases (mapks) are highly conserved in eukaryotic organisms. in pathogenic fungi, their activities were assigned to different physiological functions including drug adaptation and resistance. aspergillus fumigatus is a human pathogenic fungus, which causes life-threatening invasive infections. therapeutic options against invasive mycoses are still limited. one of the clinically used drugs is caspofungin, which specifically targets the fungal cell wall biosynthesis. a s ...201526356475
molecular identification and amphotericin b susceptibility testing of clinical isolates of aspergillus from 11 hospitals in korea.we investigated the species distribution and amphotericin b (amb) susceptibility of korean clinical aspergillus isolates by using two etests and the clsi broth microdilution method.201526354348
poly(lactic acid)/tio₂ nanocomposites as alternative biocidal and antifungal materials.poly(lactic acid) (pla) composites with titanium oxide (tio2) ~10-nm nanoparticles were produced by the melting process and their main properties were evaluated. the nanoparticles are homogeneously dispersed in the matrix with a low degree of agglomeration, as seen by transmission electron microscopy (tem). the crystallinity temperature increased ~12% when 5 wt.% of tio2 was added, showing that the nanoparticles acted as nucleating agents this trend was confirmed by optical images. the elastic m ...201526354270
aspergillus biofilm in vitro and in vivo.in vivo, aspergillus fumigatus grows as a typical biofilm with hyphae covered by an extracellular matrix (ecm) composed of polysaccharides, galactomannan, and galactosaminogalactan. α1,3 glucans and melanin are also constitutive of the ecm in aspergilloma but not in invasive aspergillosis. in vitro, two biofilm models were established to mimic the in vivo situation. the first model (model 1) uses submerged liquid conditions and is characterized by slow growth, while the second model (model 2) us ...201526350307
comparison of the microbicidal activity of monochloramine and iodine.recently, we showed that monochloramine (nh2 cl) has a significantly stronger bactericidal and fungicidal activity than chloramine t despite its lower oxidizing power. this phenomenon was explained by increased penetration because of the higher lipophilicity and smaller bulk of nh2 cl. as iodine (i2 ) has an even fivefold higher bulk than nh2 cl, a comparison of both compounds regarding their microbicidal activity became the aim of this study. aqueous solutions of i2 at a concentration of 10·7 μ ...201526347484
identification and characterization of a novel galactofuranose-specific β-d-galactofuranosidase from streptomyces species.β-d-galactofuranose (galf) is a component of polysaccharides and glycoconjugates and its transferase has been well analyzed. however, no β-d-galactofuranosidase (galf-ase) gene has been identified in any organism. to search for a galf-ase gene we screened soil samples and discovered a strain, identified as a streptomyces species by the 16s ribosomal rna gene analysis, that exhibits galf-ase activity for 4-nitrophenyl β-d-galactofuranoside (pnp-β-d-galf) in culture supernatants. by draft genome s ...201526340350
cyp51a gene silencing using rna interference in azole-resistant aspergillus fumigatus.an increasing number of reports have described the emergence of acquired resistance of aspergillus fumigatus to azole compounds. the primary mechanism of resistance in clinical isolates is the mutation of the azole drug target enzyme, which is encoded by the cyp51a gene. the aim of this study was to evaluate the impact of silencing the cyp51a gene in azole-resistant a. fumigatus isolates. a 21-nucleotide small-interfering rna (sirna) was designed based on the cdna sequence of the a. fumigatus cy ...201526448519
secondary metabolites from aspergillus fumigatus, an endophytic fungus from the liverwort heteroscyphus tener (steph.) schiffn.three new metabolites, asperfumigatin (1), isochaetominine (10), and 8'-o-methylasterric acid (21), together with nineteen known compounds, were obtained from the culture of aspergillus fumigatus, an endophytic fungus from the chinese liverwort heteroscyphus tener (steph.) schiffn. their structures were established by extensive analysis of the spectroscopic data. the absolute configurations of 1 and 10 were determined by analysis of their respective cd spectra. cytotoxicity of these isolates aga ...201526363876
indoleamine 2,3-dioxygenase is involved in the inflammation response of corneal epithelial cells to aspergillus fumigatus infections.indoleamine 2,3-dioxygenase (ido), which is mainly expressed in activated dendritic cells, is known as a regulator of immune responses. however, the role of ido in immune responses against fungal corneal infection has not been investigated. to evaluate the regulatory mechanisms of ido in fungal inflammation, we resorted to human corneal epithelial cells (hcecs), known as the first barrier of cornea against pathogenic microorganisms. we found that ido was significantly up-regulated in corneal epi ...201526361229
in vivo efficacy of voriconazole and posaconazole therapy in a novel invertebrate model of aspergillus fumigatus infection.the emergence of azole resistance in aspergillus fumigatus is a clinically important issue in the management of invasive aspergillosis as it could limit therapeutic options. accurate measurement of in vitro antifungal activity in terms of minimum inhibitory concentration (mic) is considered of clinical relevance and often gives useful therapeutic information for physicians. however, the lack of in vitro-in vivo correlation is frequent and the observed in vitro phenotype does not always correlate ...201526358971
endoperoxide formation by an α-ketoglutarate-dependent mononuclear non-haem iron enzyme.many peroxy-containing secondary metabolites have been isolated and shown to provide beneficial effects to human health. yet, the mechanisms of most endoperoxide biosyntheses are not well understood. although endoperoxides have been suggested as key reaction intermediates in several cases, the only well-characterized endoperoxide biosynthetic enzyme is prostaglandin h synthase, a haem-containing enzyme. fumitremorgin b endoperoxidase (ftmox1) from aspergillus fumigatus is the first reported α-ke ...201526524521
antifungal activity of myriocin on clinically relevant aspergillus fumigatus strains producing biofilm.the human pathogenic mold aspergillus fumigatus is able to form a complex biofilm embedded in extracellular matrix. biofilms confer antimicrobial resistance and it is well known that aspergillosis is often refractory to the conventional antifungal therapy. the treatment of biofilm-related infections poses a significant clinical challenge on a daily basis, promoting the search for new therapeutic agents. our aim was to exploit the modulation of sphingolipid mediators as new therapeutic target to ...201526519193
single-tube pcr coupled with mini-sequencing assay for the detection of cyp51a and cyp51b polymorphisms in aspergillus fumigatus.triazole resistance in aspergillus fumigatus is associated with mutations in cyp51 genes, therefore, a single-tube multiplex pcr was proposed for rapid detection of such mutations.201526515651
pharmacodynamics of isavuconazole in a dynamic in vitro model of invasive pulmonary aspergillosis.isavuconazonium sulfate is a novel triazole prodrug that has been recently approved for the treatment of invasive aspergillosis by the fda. the active moiety (isavuconazole) has a broad spectrum of activity against many pathogenic fungi. this study utilized a dynamic in vitro model of the human alveolus to describe the pharmacodynamics of isavuconazole against two wild-type and two previously defined azole-resistant isolates of aspergillus fumigatus. a human-like concentration-time profile for i ...201526503648
[invasive aspergillosis accompanied by a subcutaneous nodular lesion].we report herein on a case of invasive aspergillosis accompanied by a subcutaneous nodular lesion. a 74-years-old male with myelodysplastic syndrome was hospitalized due to high fever and a painful subcutaneous nodule on the left thigh. chest radiography and ct scans showed multiple nodular lesions of both lungs, and bacterial pneumonia was initially suspected. he was treated with meropenem, but the symptoms did not subside. three days after admission, we found that β-d-glucan levels were elevat ...201526552133
differential support of aspergillus fumigatus morphogenesis by yeast and human actins.the actin cytoskeleton is highly conserved among eukaryotes and is essential for cellular processes regulating growth and differentiation. in fungi, filamentous actin (f-actin) orchestrates hyphal tip structure and extension via organization of exocytic and endocytic processes at the hyphal tip. although highly conserved, there are key differences among actins of fungal species as well as between mammalian and fungal actins. for example, the f-actin stabilizing molecules, phalloidin and jasplaki ...201526555617
azole resistance in aspergillus fumigatus clinical isolates from an italian culture collection.the aims of the study were to investigate the prevalence of azole resistance among aspergillus fumigatus clinical isolates. a total of 533 clinical isolates that had been collected between 1995 and 2006, from 441 patients, were screened. no resistance was detected in isolates collected between 1995 and 1997. starting in 1998, the resistance rate was 6.9%; a total of 24 patients (6.25%) harbored a resistant isolate. the tr34/l98h substitution was found in 21 of 30 tested isolates.201526552980
chronic necrotizing pulmonary aspergillosis in an immunocompetent, obese 10-year-old boy.chronic necrotizing pulmonary aspergillosis is a rare form of pulmonary aspergillosis. it is usually seen in middle-aged or elderly patients with underlying chronic lung disease or mild immunodeficiency, and has been only rarely encountered in children. clinical presentation is variable and usually involves constitutional symptoms of several months' duration as well as respiratory symptoms. we present a previously well, immunocompetent, obese 10-year-old boy with cough and mild hemoptysis lastin ...201526388598
antifungal activity of selenium nanoparticles synthesized by bacillus species msh-1 against aspergillus fumigatus and candida albicans.fungal infections affect various parts of the body and can be difficult to treat. aspergillus infection causes a spectrum of diverse diseases particularly in lung according to host immunity. the two major entities are invasive pulmonary aspergillosis and chronic pulmonary aspergillosis. candida infections can be superficial or invasive. superficial infections often affect the skin or mucous membranes. however, invasive fungal infections are often life-threatening. advances in nanotechnology have ...201526495111
[resistant fungi].particularly in the area of hematology/oncology and intensive care medicine, infections due to resistant fungi are to be expected. emergence of resistance in fungi is a less dynamic process than in bacteria; it can, however, have an equally important impact on treatment strategies. in the following article, the most important resistance patterns of yeasts and molds (candida albicans , aspergillus fumigatus, the order mucorales and the genus fusarium) will be presented and discussed. their diagno ...201526432089
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