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the diagnostic criteria for allergic bronchopulmonary aspergillosis in children with poorly controlled asthma need to be re-evaluated.the aim of this study was to examine the association between allergic bronchopulmonary aspergillosis (abpa) and poorly controlled asthma in children and appraise the diagnostic criteria.201525620428
the three-dimensional structure of the cellobiohydrolase cel7a from aspergillus fumigatus at 1.5 å resolution.the enzymatic degradation of plant cell-wall cellulose is central to many industrial processes, including second-generation biofuel production. key players in this deconstruction are the fungal cellobiohydrolases (cbhs), notably those from family gh7 of the carbohydrate-active enzymes (cazy) database, which are generally known as cbhi enzymes. here, three-dimensional structures are reported of the aspergillus fumigatus cbhi cel7a solved in uncomplexed and disaccharide-bound forms at resolutions ...201525615982
evaluation of mold exposure in cystic fibrosis patients' dwellings and allergic bronchopulmonary risk.very few studies have been conducted on cystic fibrosis (cf) patients' exposure to the indoor environment and, to our knowledge, there are no studies dealing with the link between specific fungal environmental exposure at home and fungal colonization resulting in allergic bronchopulmonary aspergillosis (abpa). fungal exposure of cf adult patients with abpa (n=4) with fungal sensitization (n=7) and with no abpa (n=5) was assessed in 16 homes by dust sampling with electrostatic dust fall collector ...201525612900
the serum opsonin l-ficolin is detected in lungs of human transplant recipients following fungal infections and modulates inflammation and killing of aspergillus fumigatus.invasive aspergillosis (ia) is a life-threatening systemic fungal infection in immunocompromised individuals that is caused by aspergillus fumigatus. the human serum opsonin, l-ficolin, has been observed to recognize a. fumigatus and could participate in fungal defense.201525612732
in vitro activity of 23 tea extractions and epigallocatechin gallate against candida species.in this study, we investigate the susceptibility of candida albicans, candida glabrata, candida krusei, candida parapsilosis, candida tropicalis, and aspergillus fumigatus using the eucast microdilution minimum inhibitory concentration (mic) method (final tea supernatant concentration range 5.0-0.005 mg/ml) to 23 different teas and tea catechins including epigallocatechin gallate (egcg) isolated from green tea. all teas exhibited potent in vitro antifungal activity against c. glabrata. six out o ...201525605775
rate of cyp51a mutation in aspergillus fumigatus among lung transplant recipients with targeted prophylaxis.the most common mechanism of azole (itraconazole and voriconazole) resistance in aspergillus fumigatus is a mutation at the cyp51a locus. the aim of our study was to determine the rate of cyp51a mutations in lung transplant recipients (ltr) undergoing targeted antifungal prophylaxis with 12 weeks of voriconazole.201525604745
epidemiology of invasive fungal infections in lung transplant recipients on long-term azole antifungal prophylaxis.lung transplant recipients (ltr) at our institution receive prolonged and mostly lifelong azole antifungal (af) prophylaxis. the impact of this prophylactic strategy on the epidemiology and outcome of invasive fungal infections (ifi) is unknown. this was a single-center, retrospective cohort study. we reviewed the medical records of all adult ltr from january 2002 to december 2011. overall, 16.5% (15 of 91) of patients who underwent lung transplantation during this time period developed ifi. nin ...201525604399
physiological behaviour of gliotoxigenic aspergillus fumigatus sensu stricto isolated from maize silage under simulated environmental conditions.environmental conditions play a key role in fungal development. during the silage production process, humidity, oxygen availability and ph vary among lactic-fermentation phases and among different silage sections. the aim of this work was to study the physiological behaviour of gliotoxicogenic aspergillus fumigatus strains isolated from maize silage under simulated natural physicochemical conditions - different water activities (a(w)), temperatures (tº), ph and oxygen pressure - on the growth pa ...201525599419
high osmolarity glycerol response ptcb phosphatase is important for aspergillus fumigatus virulence.aspergillus fumigatus is a fungal pathogen that is capable of adapting to different host niches and to avoid host defenses. an enhanced understanding of how, and which, a. fumigatus signal transduction pathways are engaged in the regulation of these processes is essential for the development of improved disease control strategies. protein phosphatases are central to numerous signal transduction pathways. to comprehend the functions of protein phosphatases in a. fumigatus, 32 phosphatase catalyti ...201525597841
genetic control of asexual development in aspergillus fumigatus.aspergillus fumigatus is one of the most common fungi found in the environment. it is an opportunistic human pathogen causing invasive pulmonary aspergillosis with a high mortality rate in immunocompromised patients. conidia, the asexual spores, serve as the main dispersal and infection agent allowing entrance of the fungus into the host through the respiratory tract. therefore, understanding the asexual developmental process that gives rise to the conidia is of great interest to the scientific ...201525596030
an alkaloid and a steroid from the endophytic fungus aspergillus fumigatus.two new compounds, fumitremorgin 12-methoxy-13-[5'-hydroxy-2'-(1''-hydroxy-3''-methoxy-5''-methylbenzoyl)-3'-methoxy]benzoic acid methyl ester (fumitremorgin d, 1) and 4,8,10,14-tetramethyl-6-acetoxy-14-[16-acetoxy-19-(20,21-dimethyl)-18-ene]-phenanthrene-1-ene-3,7-dione (2) were isolated from the cultured endophytic isolated fungus aspergillus fumigatus, together with fourteen known compounds. their structures were elucidated by 1-d and 2-d nmr analyses. the cytotoxicity profile of the compound ...201525594349
efficacy of oleylphosphocholine (olpc) in vitro and in a mouse model of invasive aspergillosis.invasive aspergillosis (ia) has become increasingly common and is characterised by high morbidity and mortality. upcoming resistance threatens treatment with azoles and highlights the continuous need for novel therapeutics. this laboratory study investigated the in vitro and in vivo potential of the alkylphospholipid oleylphosphocholine (olpc) against aspergillus. in vitro activities of olpc, miltefosine, posaconazole and voriconazole were determined for aspergillus fumigatus, a. niger, a. terre ...201525590577
the strength of synergistic interaction between posaconazole and caspofungin depends on the underlying azole resistance mechanism of aspergillus fumigatus.the majority of azole resistance mechanisms in aspergillus fumigatus correspond to mutations in the cyp51a gene. as azoles are less effective against infections caused by multiply azole-resistant a. fumigatus isolates, new therapeutic options are warranted for treating these infections. we therefore investigated the in vitro combination of posaconazole (posa) and caspofungin (cas) against 20 wild-type and resistant a. fumigatus isolates with 10 different resistance mechanisms. fungal growth was ...201525583716
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
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
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
improved production of reducing sugars from rice straw using crude cellulase activated with fe₃o₄/alginate nanocomposite.effect of fe3o4 nanoparticles (nps) and fe3o4/alginate nanocomposites (ncs) have been investigated on production and thermostability of crude cellulase enzyme system obtained by newly isolated thermotolerant aspergillus fumigatus aa001. fe3o4 nps and fe3o4/alginate ncs have been synthesized by co-precipitation method and characterized through various techniques. in presence of fe3o4 nps and fe3o4/alginate ncs, filter paper activity of crude cellulase was increased about 35% and 40%, respectively ...201525740000
secondary metabolite profiles and antifungal drug susceptibility of aspergillus fumigatus and closely related species, aspergillus lentulus, aspergillus udagawae, and aspergillus viridinutans.the incidence of aspergillus infection has been increasing in the past few years. also, new aspergillus fumigatus-related species, namely aspergillus lentulus, aspergillus udagawae, and aspergillus viridinutans, were shown to infect humans. these fungi exhibit marked morphological similarities to a. fumigatus, albeit with different clinical courses and antifungal drug susceptibilities. the present study used liquid chromatography/time-of-flight mass spectrometry to identify the secondary metabol ...201525737146
reduced risk of nontuberculous mycobacteria in cystic fibrosis adults receiving long-term azithromycin.azithromycin reduces exacerbations in cystic fibrosis (cf) patients. our aim was to investigate its association with nontuberculous mycobacteria isolation and macrolide susceptibility.201525735458
comparative proteomics of a tor inducible aspergillus fumigatus mutant reveals involvement of the tor kinase in iron regulation.the tor (target of rapamycin) kinase is one of the major regulatory nodes in eukaryotes. here, we analyzed the tor kinase in aspergillus fumigatus, which is the most important airborne fungal pathogen of humans. because deletion of the single tor gene was apparently lethal, we generated a conditional lethal tor mutant by replacing the endogenous tor gene by the inducible xylp-tor gene cassette. by both 2de and gel-free lc-ms/ms, we found that tor controls a variety of proteins involved in nutrie ...201525728394
quantitative proteomic study of aspergillus fumigatus secretome revealed deamidation of secretory enzymes.aspergillus sp. plays an essential role in lignocellulosic biomass recycling and is also exploited as cell factories for the production of industrial enzymes. this study profiled the secretome of aspergillus fumigatus when grown with cellulose, xylan and starch by high throughput quantitative proteomics using isobaric tags for relative and absolute quantification (itraq). post translational modifications (ptms) of proteins play a critical role in protein functions. however, our understanding of ...201525724730
de novo induction of resistance against voriconazole in aspergillus fumigatus. 201527873654
identification and deletion of tft1, a predicted glycosyltransferase necessary for cell wall β-1,3;1,4-glucan synthesis in aspergillus fumigatus.aspergillus fumigatus is an environmental mold that causes severe, often fatal invasive infections in immunocompromised patients. the search for new antifungal drug targets is critical, and the synthesis of the cell wall represents a potential area to find such a target. embedded within the main β-1,3-glucan core of the a. fumigatus cell wall is a mixed linkage, β-d-(1,3;1,4)-glucan. the role of this molecule or how it is synthesized is unknown, though it comprises 10% of the glucans within the ...201525723175
biologically active metabolites produced by the basidiomycete quambalaria cyanescens.four strains of the fungus quambalaria cyanescens (basidiomycota: microstromatales), were used for the determination of secondary metabolites production and their antimicrobial and biological activities. a new naphthoquinone named quambalarine a, (s)-(+)-3-(5-ethyl-tetrahydrofuran-2-yliden)-5,7,8-trihydroxy-2-oxo-1,4-naphthoquinone (1), together with two known naphthoquinones, 3-hexanoyl-2,5,7,8-tetrahydroxy-1,4-naphthoquinone (named here as quambalarine b, 2) and mompain, 2,5,7,8-tetrahydroxy-1 ...201525723150
[invasive pulmonary aspergillosis in influenza].invasive pulmonary aspergillosis (ipa) is a life-threatening infection that occurs predominantly in severely immunocompromised patients. recently, ipa is also increasingly seen in less severely immunocompromised patients, such as patients with copd receiving glucocorticoids and patients on ventilation in an ic unit.201525714763
multiple mechanisms contribute to the development of clinically significant azole resistance in aspergillus fumigatus.infections caused by the filamentous fungus aspergillus fumigatus are a significant clinical issue and represent the second most-common form of fungal infection. azole drugs are effective against this pathogen but resistant isolates are being found more frequently. infections associated with azole resistant a. fumigatus have a significantly increased mortality making understanding drug resistance in this organism a priority. the target of azole drugs is the lanosterol α-14 demethylase enzyme enc ...201525713565
allergic bronchopulmonary aspergillosis in children.allergic bronchopulmonary aspergillosis (abpa) is a disease of the lungs resulting from a hypersensitivity reaction to spores of aspergillus fumigatus. here we report the case of a 13-year-old girl with abpa who presented with productive cough, bronchiectasis and decline in lung function, and review the clinical features and treatment for pediatric abpa.201525712512
pharmacodynamics of amphotericin b deoxycholate, amphotericin b lipid complex, and liposomal amphotericin b against aspergillus fumigatus.amphotericin b is a first-line agent for the treatment of invasive aspergillosis. however, relatively little is known about the pharmacodynamics of amphotericin b for invasive pulmonary aspergillosis. we studied the pharmacokinetics (pk) and pharmacodynamics (pd) of amphotericin b deoxycholate (damb), amphotericin b lipid complex (ablc), and liposomal amphotericin b (lamb) by using a neutropenic-rabbit model of invasive pulmonary aspergillosis. the study endpoints were lung weight, infarct score ...201525712363
a rare pigmented keratitis caused by aspergillus fumigatus. 201525709935
early expression of mannose-binding lectin 2 during aspergillus fumigatus infection in human corneal epithelial cells.to evaluate the early expression of mannose-binding lectin 2 (mbl2) in human corneal epithelial cells (hcecs) infected by aspergillus fumigatus (af).201525709904
n-myristoyltransferase is a cell wall target in aspergillus fumigatus.treatment of filamentous fungal infections relies on a limited repertoire of antifungal agents. compounds possessing novel modes of action are urgently required. n-myristoylation is a ubiquitous modification of eukaryotic proteins. the enzyme n-myristoyltransferase (nmt) has been considered a potential therapeutic target in protozoa and yeasts. here, we show that the filamentous fungal pathogen aspergillus fumigatus possesses an active nmt enzyme that is essential for survival. surprisingly, par ...201525706802
chitin recognition via chitotriosidase promotes pathologic type-2 helper t cell responses to cryptococcal infection.pulmonary mycoses are often associated with type-2 helper t (th2) cell responses. however, mechanisms of th2 cell accumulation are multifactorial and incompletely known. to investigate th2 cell responses to pulmonary fungal infection, we developed a peptide-mhcii tetramer to track antigen-specific cd4+ t cells produced in response to infection with the fungal pathogen cryptococcus neoformans. we noted massive accruement of pathologic cryptococcal antigen-specific th2 cells in the lungs following ...201525764512
histone deacetylase inhibition as an alternative strategy against invasive aspergillosis.invasive aspergillosis (ia) is a life-threatening infection due to aspergillus fumigatus and other aspergillus spp. drugs targeting the fungal cell membrane (triazoles, amphotericin b) or cell wall (echinocandins) are currently the sole therapeutic options against ia. their limited efficacy and the emergence of resistance warrant the identification of new antifungal targets. histone deacetylases (hdacs) are enzymes responsible of the deacetylation of lysine residues of core histones, thus contro ...201525762988
[epidural abscess due to aspergillus fumigatus with compression of the optic nerve]. 201525760724
structural insights into aspergillus fumigatus lectin specificity: afl binding sites are functionally non-equivalent.the aspergillus fumigatus lectin afl was recently described as a new member of the aal lectin family. as a lectin from an opportunistic pathogen, it might play an important role in the interaction of the pathogen with the human host. a detailed study of structures of afl complexed with several monosaccharides and oligosaccharides, including blood-group epitopes, was combined with affinity data from spr and discussed in the context of previous findings. its six binding sites are non-equivalent, a ...201525760594
pharmacodynamics of isavuconazole in an aspergillus fumigatus mouse infection model.azole resistance is an emerging problem in aspergillus fumigatus which translates into treatment failure. alternative treatments with new azoles may improve therapeutic outcome in invasive aspergillosis (ia) even for strains with decreased susceptibility to current azoles. the in vivo efficacy of 0.25, 1, 4, 16, 64, 128, 256, and 512 mg/kg of body weight/day prodrug isavuconazonium sulfate (bal8557) (isavuconazole [isa]-equivalent doses of 0.12, 0.48, 1.92, 7.68, 30.7, 61.4, 122.9, and 245.8 mg/ ...201525753636
pulmonary aspergillosis.aspergillosis is a mycotic disease usually caused by aspergillus fumigatus, a saprophytic and ubiquitous airborne fungus. aspergillus-related lung diseases are traditionally classified into four different forms, whose occurrence depends on the immunologic status of the host and the existence of an underlying lung disease. allergic broncho-pulmonary aspergillosis (abpa) affects patients with asthma or cystic fibrosis. saprophytic infection (aspergilloma) occurs in patients with abnormal airways ( ...201525753544
aspergillus, angiogenesis, and obesity: the story behind beloranib.fumagillin, an antimicrobial compound first isolated in 1949 from the fungus aspergillus fumigatus, four decades later was unexpectedly found to inhibit angiogenesis. interest in developing angiogenesis inhibitor drugs as possible treatments for cancer led to the synthesis of analogs of fumagillin. preclinical studies of various analog drugs confirmed that they inhibited angiogenesis, but they also were associated with weight loss as an adverse effect. because adipose tissue can grow and regress ...201525751824
immune reconstitution after allogeneic hematopoietic stem cell transplantation and association with occurrence and outcome of invasive aspergillosis.invasive aspergillosis (ia) remains a leading cause of morbidity and mortality in patients receiving allogeneic hematopoietic stem cell transplantation (hsct). to date, no reliable immunological biomarkers for management and outcome of ia exist. here, we investigated reconstitution of antifungal immunity in patients during the first 12 months after hsct and correlated it with ia.201525748323
concerted activation of the aim2 and nlrp3 inflammasomes orchestrates host protection against aspergillus infection.invasive pulmonary aspergillosis is a leading cause of infection-associated mortality in immunocompromised individuals. aspergillus fumigatus infection produces ligands that could activate inflammasomes, but the contribution of these host defenses remains unclear. we show that two inflammasome receptors, aim2 and nlrp3, recognize intracellular a. fumigatus and collectively induce protective immune responses. mice lacking both aim2 and nlrp3 fail to confine aspergillus hyphae to inflammatory foci ...201525704009
hyaluronan stimulates ex vivo b lymphocyte chemotaxis and cytokine production in a murine model of fungal allergic asthma.allergic asthma is a chronic inflammatory disease of the airways characterized by excessive eosinophilic and lymphocytic inflammation with associated changes in the extracellular matrix (ecm) resulting in airway wall remodeling. hyaluronan (ha) is a nonsulfated glycosaminoglycan ecm component that functions as a structural cushion in its high molecular mass (hmm) but has been implicated in metastasis and other disease processes when it is degraded to smaller fragments. however, relatively little ...201525698348
kexin-like endoprotease kexb is required for n-glycan processing, morphogenesis and virulence in aspergillus fumigatus.kexin-like proteins belong to the subtilisin-like family of the proteinases that cleave secretory proproteins to their active forms. several fungal kexin-like proteins have been investigated. the mutants lacking of kexin-like protein display strong phenotypes such as cell wall defect, abnormal polarity, and, in case of candida albicans, diminished virulence. however, only several proteins have been confirmed as the substrates of kexin-like proteases in these fungal species. it still remains uncl ...201525687931
virulence determinants of the human pathogenic fungus aspergillus fumigatus protect against soil amoeba predation.filamentous fungi represent classical examples for environmentally acquired human pathogens whose major virulence mechanisms are likely to have emerged long before the appearance of innate immune systems. in natural habitats, amoeba predation could impose a major selection pressure towards the acquisition of virulence attributes. to test this hypothesis, we exploited the amoeba dictyostelium discoideum to study its interaction with aspergillus fumigatus, two abundant soil inhabitants for which w ...201525684622
epidemiology of filamentous fungal infections in burned patients: a french retrospective study.filamentous fungal infections (ffi) seem to become more frequent in burn patients, in whom they are usually accepted to cause severe. however published data regarding their incidence and consequences in that context remain scarce. the aim of this study was to evaluate the incidence of mould infections in our burn centre, and to review characteristics and outcomes of patients with such infections.201525681957
clinical and allergic sensitization characteristics of allergic rhinitis among the elderly population in istanbul, turkey.prevalence of allergic rhinitis (ar) in elderly population in turkey is not known. studies on the prevalence and features of allergy in older adults are needed to identify safe and effective diagnostic/therapeutic methods for elderly ar patients. we aimed to identify the clinical and allergic characteristics of sensitization to aeroallergens among individuals aged ≥60 years with allergic rhinitis admitted to an allergy outpatient clinic in istanbul. of 109 patients, 33.9 % were atopic. sixty-fiv ...201525680346
effective neutrophil phagocytosis of aspergillus fumigatus is mediated by classical pathway complement activation.aspergillus fumigatus is an important airborne fungal pathogen and a major cause of invasive fungal infections. susceptible individuals become infected via the inhalation of dormant conidia. if the immune system fails to clear these conidia, they will swell, germinate and grow into large hyphal structures. neutrophils are essential effector cells for controlling a. fumigatus infection. in general, opsonization of microbial particles is crucial for efficient phagocytosis and killing by neutrophil ...201525676601
pseudomonas aeruginosa manipulates redox and iron homeostasis of its microbiota partner aspergillus fumigatus via phenazines.the opportunistic fungal pathogen aspergillus fumigatus is increasingly found as a coinfecting agent along with pseudomonas aeruginosa in cystic fibrosis patients. amongst the numerous molecules secreted by p. aeruginosa during its growth, phenazines constitute a major class. p. aeruginosa usually secreted four phenazines, pyocyanin (pyo), phenazine-1-carboxamide (pcn), 1-hydroxyphenazine (1-hp) and phenazine-1-carboxylic acid (pca). these phenazines inhibited the growth of a. fumigatus but the ...201525665925
airway hyper-responsiveness to mannitol provides a good evaluation of atopy in childhood asthma.the relationship between airway hyper-responsiveness (ahr) and atopy has been previously investigated, but there are still some issues to be clarified. the aim of this study was to assess the link between ahr and mannitol and atopy in asthmatic children.201525661794
differential gene expression in aspergillus fumigatus induced by human platelets in vitro.invasive aspergillosis is characterized by vascular invasion and thrombosis. in order to determine the antifungal activity of human platelets, hyphal elongation and metabolic activity of a clinical a. fumigatus isolate were measured. genome-wide identification of differentially expressed genes in a. fumigatus was performed after exposure to platelets for 15, 30, 60 and 180 min. data were analyzed by gene ontology annotation as well as functional categories (funcat) and kegg enrichment analyses. ...201525661519
recognition of aspergillus fumigatus hyphae by human plasmacytoid dendritic cells is mediated by dectin-2 and results in formation of extracellular traps.plasmacytoid dendritic cells (pdcs) were initially considered as critical for innate immunity to viruses. however, our group has shown that pdcs bind to and inhibit the growth of aspergillus fumigatus hyphae and that depletion of pdcs renders mice hypersusceptible to experimental aspergillosis. in this study, we examined pdc receptors contributing to hyphal recognition and downstream events in pdcs stimulated by a. fumigatus hyphae. our data show that dectin-2, but not dectin-1, participates in ...201525659141
coccidioides endospores and spherules draw strong chemotactic, adhesive, and phagocytic responses by individual human neutrophils.coccidioides spp. are dimorphic pathogenic fungi whose parasitic forms cause coccidioidomycosis (valley fever) in mammalian hosts. we use an innovative interdisciplinary approach to analyze one-on-one encounters between human neutrophils and two forms of coccidioides posadasii. to examine the mechanisms by which the innate immune system coordinates different stages of the host response to fungal pathogens, we dissect the immune-cell response into chemotaxis, adhesion, and phagocytosis. our singl ...201526070210
synthesis, characterization and biological activity of schiff bases based on chitosan and arylpyrazole moiety.the schiff bases of chitosan were synthesized by the reaction of chitosan with 3-(4-substituted-phenyl)-1-phenyl-1h-pyrazole-4-carbaldehyde. the structure of the prepared chitosan derivatives was characterized by ft-ir spectroscopy, elemental analysis, and x-ray diffraction studies and thermogravimetric analysis (tg). the results show that the specific properties of schiff bases of chitosan can be altered by modifying the molecular structures with proper substituent groups.tg results reveal that ...201526067768
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
microbial ecology of a crewed rover traverse in the arctic: low microbial dispersal and implications for planetary protection on human mars missions.between april 2009 and july 2011, the nasa haughton-mars project (hmp) led the northwest passage drive expedition (nwpdx), a multi-staged long-distance crewed rover traverse along the northwest passage in the arctic. in april 2009, the hmp okarian rover was driven 496 km over sea ice along the northwest passage, from kugluktuk to cambridge bay, nunavut, canada. during the traverse, crew members collected samples from within the rover and from undisturbed snow-covered surfaces around the rover at ...201526060984
structural insights into binding of the antifungal drug fluconazole to saccharomyces cerevisiae lanosterol 14α-demethylase.infections by fungal pathogens such as candida albicans and aspergillus fumigatus and their resistance to triazole drugs are major concerns. fungal lanosterol 14α-demethylase belongs to the cyp51 class in the cytochrome p450 superfamily of enzymes. this monospanning bitopic membrane protein is involved in ergosterol biosynthesis and is the primary target of azole antifungal drugs, including fluconazole. the lack of high-resolution structural information for this drug target from fungal pathogens ...201526055382
calcium-mediated induction of paradoxical growth following caspofungin treatment is associated with calcineurin activation and phosphorylation in aspergillus fumigatus.the echinocandin antifungal drug caspofungin at high concentrations reverses the growth inhibition of aspergillus fumigatus, a phenomenon known as the "paradoxical effect," which is not consistently observed with other echinocandins (micafungin and anidulafungin). previous studies of a. fumigatus revealed the loss of the paradoxical effect following pharmacological or genetic inhibition of calcineurin, yet the underlying mechanism is poorly understood. here, we utilized a codon-optimized biolumi ...201526055379
hitting the caspofungin salvage pathway of human-pathogenic fungi with the novel lasso peptide humidimycin (mdn-0010).fungal infections have increased dramatically in the last 2 decades, and fighting infectious diseases requires innovative approaches such as the combination of two drugs acting on different targets or even targeting a salvage pathway of one of the drugs. the fungal cell wall biosynthesis is inhibited by the clinically used antifungal drug caspofungin. this antifungal activity has been found to be potentiated by humidimycin, a new natural product identified from the screening of a collection of 2 ...201526055366
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
acute invasive pulmonary aspergillosis complicating allergic bronchopulmonary aspergillosis: case report and systematic review.aspergillus fumigatus can cause a variety of pulmonary syndromes including allergic bronchopulmonary aspergillosis (abpa), chronic pulmonary aspergillosis and invasive pulmonary aspergillosis (ipa). occurrence of ipa and abpa in the same patient is rare as the risk factors for abpa and ipa are different. we describe a 45-year-old male with abpa treated with oral methylprednisolone and itraconazole, who developed acute respiratory failure secondary to ipa, a month later. the patient subsequently ...201526045286
an evaluation of antifungal agents for the treatment of fungal contamination in indoor air environments.fungal contamination in indoor environments has been associated with adverse health effects for the inhabitants. remediation of fungal contamination requires removal of the fungi present and modifying the indoor environment to become less favourable to growth.  this may include treatment of indoor environments with an antifungal agent to prevent future growth. however there are limited published data or advice on chemical agents suitable for indoor fungal remediation. the aim of this study was t ...201526042369
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
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
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
the role of a phospholipase (pld) in virulence of purpureocillium lilacinum (paecilomyces lilacinum).phospholipases are key enzymes in pathogenic fungi that cleave host phospholipids, resulting in membrane destabilization and host cell penetration. however, understanding the role of phospholipases on the virulence of the filamentous fungus purpureocillium lilacinum has been still rather limited. in this study, pld gene was characterized. it encodes the protein phospholipase d (pld) in p. lilacinum. this gene, 3303 bp open reading frame fragment (orf), encodes a protein of 1100 amino acids with ...201526026833
triazole-resistant aspergillus fumigatus harbouring g54 mutation: is it de novo or environmentally acquired?triazole resistance in aspergillus fumigatus develops in patients with chronic lung diseases receiving long-term azole therapy or by environmental selection of resistant a. fumigatus. here we report for the first time the isolation of triazole-resistant a. fumigatus (traf) harbouring the g54e mutation from environmental samples in india, romania and tanzania. this mutation in the cyp51a azole target gene of a. fumigatus is so far considered as de novo occurring in patients due to prolonged expos ...201527873672
prospective evaluation of azole resistance in aspergillus fumigatus clinical isolates in france.several studies, especially in europe, have recently reported the emerging phenomenon of azole resistance in aspergillus fumigatus, but very few data are available in france. our study aimed to determine the resistance prevalence in a. fumigatus isolates recovered from clinical samples over a 1-year period in two university hospital centers.201526026171
polymorphonuclear neutrophils and granulocytic myeloid-derived suppressor cells inhibit natural killer cell activity toward aspergillus fumigatus.invasive aspergillosis is a devastating infectious disease in immunocompromised patients. besides neutrophils and macrophages, natural killer (nk) cells have recently emerged as important players in immunity to this infection. it was shown that nk cells comprise an essential role in the clearance of aspergillus fumigatus (a. fumigatus) in neutropenic but not in nonneutropenic mice. however, the antifungal activity of nk cells and their regulation have not been fully characterized. in this study, ...201526026170
hsp70 and the cochaperone stia (hop) orchestrate hsp90-mediated caspofungin tolerance in aspergillus fumigatus.aspergillus fumigatus is the primary etiologic agent of invasive aspergillosis (ia), a major cause of death among immunosuppressed patients. echinocandins (e.g., caspofungin) are increasingly used as second-line therapy for ia, but their activity is only fungistatic. heat shock protein 90 (hsp90) was previously shown to trigger tolerance to caspofungin and the paradoxical effect (i.e., decreased efficacy of caspofungin at higher concentrations). here, we demonstrate the key role of another molec ...201526014950
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
integrated inference and evaluation of host-fungi interaction networks.fungal microorganisms frequently lead to life-threatening infections. within this group of pathogens, the commensal candida albicans and the filamentous fungus aspergillus fumigatus are by far the most important causes of invasive mycoses in europe. a key capability for host invasion and immune response evasion are specific molecular interactions between the fungal pathogen and its human host. experimentally validated knowledge about these crucial interactions is rare in literature and even spec ...201526300851
an in vitro and in vivo study on the synergistic effect and mechanism of itraconazole or voriconazole alone and in combination with tetrandrine against aspergillus fumigatus.in this study, we investigated the in vitro antifungal effects of itraconazole/voriconazole (itr/vrc) alone and in combination with tetrandrine (tet) against 23 clinical isolates of a. fumigatus using a chequerboard microdilution method. the dynamic antifungal effects of tet with itr/vrc against a. fumigatus were assessed in vivo using time-kill curves following systemic infection of mice with a. fumigatus. after treatment, efflux pump activity was determined by the efflux of rhodamine 6g (r6g). ...201526296880
the aspergillus fumigatus pkca g579r mutant is defective in the activation of the cell wall integrity pathway but is dispensable for virulence in a neutropenic mouse infection model.aspergillus fumigatus is an opportunistic human pathogen, which causes the life-threatening disease, invasive pulmonary aspergillosis. in fungi, cell wall homeostasis is controlled by the conserved cell wall integrity (cwi) pathway. in a. fumigatus this signaling cascade is partially characterized, but the mechanisms by which it is activated are not fully elucidated. in this study we investigated the role of protein kinase c (pkca) in this signaling cascade. our results suggest that pkca is an e ...201526295576
investigating the presence of fungal agents in febrile neutropenic patients using different microbiological, serological, and molecular methods.this study aimed to investigate fungal agents in febrile neutropenic patients with hematological malignancies. direct microscopy and cultures were performed on clinical samples collected from febrile neutropenic episodes. the galactomannan (gm) antigen was tested using enzyme-linked immunosorbent assays, and aspergillus fumigatus and candida albicans deoxyribonucleic acid (dna) assessed using real-time polymerase chain reaction (pcr) in consecutive serum samples. of the 199 episodes investigated ...201526295293
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
allergic inflammation in aspergillus fumigatus-induced fungal asthma.although fungi are pervasive in many environments, few cause disease in humans. of these, aspergillus fumigatus is particularly well suited to be a pathogen of the human lung. its physical and biological characteristics combine to provide an organism that can cause tremendous morbidity and high mortality if left unchecked. luckily, that is rarely the case. however, repeated exposure to inhaled a. fumigatus spores often results in an immune response that carries significant immunopathology, exace ...201526288940
international expert opinion on the management of infection caused by azole-resistant aspergillus fumigatus.an international expert panel was convened to deliberate the management of azole-resistant aspergillosis. in culture-positive cases, in vitro susceptibility testing should always be performed if antifungal therapy is intended. different patterns of resistance are seen, with multi-azole and pan-azole resistance more common than resistance to a single triazole. in confirmed invasive pulmonary aspergillosis due to an azole-resistant aspergillus, the experts recommended a switch from voriconazole to ...201526282594
emergence of tr46/y121f/t289a in an aspergillus fumigatus isolate from a chinese patient. 201526282417
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
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
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