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innate lung defense during invasive aspergillosis: new mechanisms.invasive aspergillosis (ia) is one of the most difficult to treat and, consequently, one of the most lethal fungal infections known to man. continued use of immunosuppressive agents during chemotherapy and organ transplantation often leads to the development of neutropenia, the primary risk factor for ia. however, ia is also becoming more appreciated in chronic diseases associated with corticosteroid therapy. the innate immune response to aspergillus fumigatus, the primary agent in ia, plays a p ...201728231567
invasive pulmonary aspergillosis in an immunocompromised patient with severe ulcerative colitis.inflammatory bowel disease patients at risk of opportunistic infections are those treated with immunomodulators. toruner and colleagues found that corticosteroid use was more commonly associated with fungal infections. we present a case of invasive pulmonary aspergillosis due to corticosteroid therapy in the context of a severe ulcerative colitis flare. we want to highlight the relationship between aspergillus fumigatus and horses; and the use of leucocitapheresis combined with mesalazine as an ...201728229616
first itraconazole resistant aspergillus fumigatus clinical isolate harbouring a g54e substitution in cyp51ap in south america.a 27-year-old male rural worker was admitted with a fungal keratitis due to an injury involving plant detritus.201728087293
α-bisabolol inhibits aspergillus fumigatus af239 growth via affecting microsomal ∆(24)-sterol methyltransferase as a crucial enzyme in ergosterol biosynthesis pathway.finding new compounds with antifungal properties is an important task due to the side effects of common antifungal drugs and emerging antifungal resistance in fungal strains. ∆(24)-sterol methyltransferase (24-smt) is a crucial enzyme that plays important roles in fungal ergosterol biosynthesis pathway and is not found in humans. in the present study, the effects of α-bisabolol on aspergillus fumigatus af239 growth and ergosterol synthesis on the base of 24-smt enzyme activity were studied; in a ...201728224386
synergistic effects of tetrandrine with posaconazole against aspergillus fumigatus.in our earlier in vitro and in vivo studies, synergistic effects were observed when itraconazole or voriconazole were combined with tetrandrine (tet) against aspergillus fumigatus, and the synergistic mechanism was related to inhibition of the drug efflux pump. posaconazole (pcz) is a broad-spectrum triazole antifungal agent used for the treatment of diverse fungal infections, including aspergillosis and candidiasis. herein, the antifungal effects of tet are further investigated in vitro and in ...201728080217
transcription factor afmac1 controls copper import machinery in aspergillus fumigatus.copper (cu) is an essential metal for all living organisms, although it is toxic in excess. filamentous fungus must acquire copper from its environment for growth. despite its essentiality for growth, the mechanisms that maintain copper homeostasis are not fully understood in filamentous fungus. to gain insights into copper homeostasis, we investigated the roles of a copper transcription factor afmac1 in the life-threatening fungus aspergillus fumigatus, a homolog of the yeast mac1. we observed ...201728215034
epigenetic modifier induced enhancement of fumiquinazoline c production in aspergillus fumigatus (ga-l7): an endophytic fungus from grewia asiatica l.present study relates to the effect of valproic acid, an epigenetic modifier on the metabolic profile of aspergillus fumigatus (ga-l7), an endophytic fungus isolated from grewia asiatica l. seven secondary metabolites were isolated from a. fumigatus (ga-l7) which were identified as: pseurotin a, pseurotin d, pseurotin f2, fumagillin, tryprostatin c, gliotoxin and bis(methylthio)gliotoxin. addition of valproic acid in the growth medium resulted in the alteration of secondary metabolic profile wit ...201728213885
sputum inflammatory mediators are increased in aspergillus fumigatus culture-positive asthmatics.aspergillus fumigatus sensitization and culture in asthma are associated with disease severity and lung function impairment, but their relationship with airway inflammation is poorly understood. we investigated the profile of 24 sputum inflammatory mediators in a. fumigatus culture-positive or-negative moderate-to-severe asthmatics. fifty-two subjects were recruited from a single center. a. fumigatus was cultured from 19 asthmatics. asthma control, symptom score, lung function, and sputum cell c ...201728102063
structure of a fungal form of aspartate-semialdehyde dehydrogenase from aspergillus fumigatus.aspartate-semialdehyde dehydrogenase (asadh) functions at a critical junction in the aspartate biosynthetic pathway and represents a validated target for antimicrobial drug design. this enzyme catalyzes the nadph-dependent reductive dephosphorylation of β-aspartyl phosphate to produce the key intermediate aspartate semialdehyde. the absence of this entire pathway in humans and other mammals will allow the selective targeting of pathogenic microorganisms for antimicrobial development. here, the x ...201728045392
high diversity of airborne fungi in the hospital environment as revealed by meta-sequencing-based microbiome analysis.invasive fungal infections acquired in the hospital have progressively emerged as an important cause of life-threatening infection. in particular, airborne fungi in hospitals are considered critical pathogens of hospital-associated infections. to identify the causative airborne microorganisms, high-volume air samplers were utilized for collection, and species identification was performed using a culture-based method and dna sequencing analysis with the illumina miseq and hiseq 2000 sequencing sy ...201728045065
first clinical isolation report of azole-resistant aspergillus fumigatus with tr34/l98h-type mutation in japan.recently, azole-resistant aspergillus fumigatus containing a 34-bp or 46-bp tandem repeat in the promoter region of cyp51a combined with amino acid substitution(s) has appeared in the environment worldwide, including several asian countries. in this study, we isolated the 34-bp tandem repeat-containing azole-resistant a. fumigatus strain okh50 from a patient in japan in may 2016. the patient had not been treated with medical azoles before the strain isolation, suggesting that the resistant prope ...201728109740
subacute invasive pulmonary aspergillosis as a rare cause of pneumothorax in immunocompetent patient: brief report.subacute invasive pulmonary aspergillosis (ipa) represents a form of chronic pulmonary aspergillosis which affects immunocompetent individuals or mildly immunocompromised persons with underlying pulmonary disease. pneumothorax can be a rare complication of subacute ipa due to a leakage of air from an air-filled lung cavitation into the pleural space. herein, we report rare and unusual case of pneumothorax in a patient with pulmonary cavity infection. a 40-year-old woman was admitted to thoracic ...201728233110
renal allograft aspergillus infection presenting with obstructive uropathy: a case report.isolated renal allograft aspergillosis is rare and usually presents with fever and decreased glomerular filtration rate. presentation with obstructive uropathy caused by aspergillus fungal balls is much less common. we report a young male patient who presented with obstructive uropathy secondary to isolated renal allograft aspergillus infection 6 weeks after transplant. he was treated with nephrectomy and antifungal medications.201728104135
etv5 regulates il-10 production in th cells.il-10 is an immunoregulatory cytokine that has broad effects across the immune system. in th cell subsets, th2 cells produce considerable amounts of il-10. the transcription factors that regulate il-10 production in th2 cells are still incompletely described. in this study, we demonstrate that the ets family transcription factor ets variant (etv)5 regulates il-10 production in th2 cells. t cell-specific etv5-deficient and littermate control mice demonstrated that il-10 production and gene expres ...201728100679
central role of il-23 and il-17 producing eosinophils as immunomodulatory effector cells in acute pulmonary aspergillosis and allergic asthma.aspergillus fumigatus causes invasive pulmonary disease in immunocompromised hosts and allergic asthma in atopic individuals. we studied the contribution of lung eosinophils to these fungal diseases. by in vivo intracellular cytokine staining and confocal microscopy, we observed that eosinophils act as local sources of il-23 and il-17. remarkably, mice lacking eosinophils had a >95% reduction in the percentage of lung il-23p19+ cells as well as markedly reduced il-23 heterodimer in lung lavage f ...201728095479
differential effects of vitamins a and d on the transcriptional landscape of human monocytes during infection.vitamin a and vitamin d are essential nutrients with a wide range of pleiotropic effects in humans. beyond their well-documented roles in cellular differentiation, embryogenesis, tissue maintenance and bone/calcium homeostasis, both vitamins have attracted considerable attention due to their association with-immunological traits. nevertheless, our knowledge of their immunomodulatory potential during infection is restricted to single gene-centric studies, which do not reflect the complexity of im ...201728094291
cipc is important for aspergillus fumigatus virulence.aspergillus fumigatus is the main causative agent of invasive aspergillosis, a disease that affects immunocompromised patients and has a high mortality rate. we previously observed that the transcription of a cipc-like gene was increased when a. fumigatus encountered an increased co2 concentration, as occurs during the infection process. cipc is a protein of unknown function that might be associated with fungal pathogenicity. in this study, the cipc gene was disrupted in a. fumigatus to evaluate ...201728120495
neutrophil interactions stimulate evasive hyphal branching by aspergillus fumigatus.invasive aspergillosis (ia), primarily caused by aspergillus fumigatus, is an opportunistic fungal infection predominantly affecting immunocompromised and neutropenic patients that is difficult to treat and results in high mortality. investigations of neutrophil-hypha interaction in vitro and in animal models of ia are limited by lack of temporal and spatial control over interactions. this study presents a new approach for studying neutrophil-hypha interaction at single cell resolution over time ...201728076396
activity of a long-acting echinocandin (cd101) and seven comparator antifungal agents tested against a global collection of contemporary invasive fungal isolates in the sentry 2014 antifungal surveillance program.the activity of cd101 and comparator antifungal agents against 606 invasive fungal isolates collected worldwide during 2014 was evaluated using the clinical and laboratory standards institute (clsi) method. all candida albicans (n = 251), candida tropicalis (n = 51), candida krusei (n = 16), and candida dubliniensis (n = 11) isolates were inhibited by ≤0.12 μg/ml of cd101 and were susceptible or showed wild-type susceptibility to the other echinocandins tested. five c. glabrata isolates (n = 100 ...201728052853
modelling the effect of ph and water activity in the growth of aspergillus fumigatus isolated from corn silage.the aim of this work was to use mathematical kinetic modelling to assess the combined effects of aw, ph, o2 availability and temperature on the growth rate and time to growth of aspergillus fumigatus strains isolated from corn silage.201728052586
a novel zn2-cys6 transcription factor atrr plays a key role in an azole resistance mechanism of aspergillus fumigatus by co-regulating cyp51a and cdr1b expressions.successful treatment of aspergillosis caused by aspergillus fumigatus is threatened by an increasing incidence of drug resistance. this situation is further complicated by the finding that strains resistant to azoles, the major antifungal drugs for aspergillosis, have been widely disseminated across the globe. to elucidate mechanisms underlying azole resistance, we identified a novel transcription factor that is required for normal azole resistance in aspergillus fungi including a. fumigatus, as ...201728052140
damage resistance protein (dap) contributes to azole resistance in a sterol-regulatory-element-binding protein srba-dependent way.the targeting of stress-response regulators has emerged as a powerful strategy to enhance azole drug efficacy and to abrogate azole drug resistance. previously, we reported that a damage resistance protein (dap) family, composed of dapa, dapb, and dapc, could respond to azole stress stimuli in aspergillus fumigatus, although the exact response mechanisms remain unknown. in this study, rna-seq analysis found that a total of 180 genes are induced by azole in a dapa-dependent manner. these genes ar ...201728050634
global population genetic analysis of aspergillus fumigatus.aspergillus fumigatus is a ubiquitous opportunistic fungal pathogen capable of causing invasive aspergillosis, a globally distributed disease with a mortality rate of up to 90% in high-risk populations. effective control and prevention of this disease require a thorough understanding of its epidemiology. however, despite significant efforts, the global molecular epidemiology of a. fumigatus remains poorly understood. in this study, we analyzed 2,026 a. fumigatus isolates from 13 countries in fou ...201728168221
the relationship between biomarkers of fungal allergy and lung damage in asthma.immunological biomarkers are the key to the diagnosis of allergic bronchopulmonary aspergillosis (abpa) and fungal sensitisation, but how these relate to clinically relevant outcomes is unclear.201727805757
aspergillus fumigatus virulence through the lens of transcription factors.invasive aspergillosis (ia), most commonly caused by the filamentous fungus aspergillus fumigatus, occurs in immune compromised individuals. the ability of a. fumigatus to proliferate in a multitude of environments is hypothesized to contribute to its pathogenicity and virulence. transcription factors (tf) have long been recognized as critical proteins for fungal pathogenicity, as many are known to play important roles in the transcriptional regulation of pathways implicated in virulence. such p ...201727816905
crispr-cas9, the new kid on the block of fungal molecular biology.research on fungal pathogens with the aim to identify virulence determinants strictly relies on the generation of defined, recombinant strains, a task that is executed by means of a sophisticated molecular biology toolbox. recent developments in fungal genome engineering have opened a new frontier by implementing the crispr-cas9 technology, based on expression of the cas9 endonuclease that is loaded by a single guiding rna (sgrna) molecule to target a defined site in the recipient genome. this n ...201727811178
the paradoxical effect of echinocandins in aspergillus fumigatus relies on recovery of the β-1,3-glucan synthase fks1.echinocandins target the fungal cell wall by inhibiting biosynthesis of the cell wall carbohydrate β-1,3-glucan. this antifungal drug class exhibits a paradoxical effect that is characterized by the resumption of growth of otherwise susceptible strains at higher drug concentrations (approximately 4 to 32 μg/ml). the nature of this phenomenon is still unknown. in this study, we analyzed the paradoxical effect of the echinocandin caspofungin on the pathogenic mold aspergillus fumigatus using a con ...201727872079
blood and tissue distribution of posaconazole in a rat model of invasive pulmonary aspergillosis.posaconazole is the recommended prophylactic agent in patients at high risk of invasive fungal infection, since adequate drug levels seem to be reached in target sites despite the relatively low levels detected in blood. the objective of this study is to obtain pharmacokinetic (pk) information associated to blood and tissue distribution of posaconazole in an animal model of invasive pulmonary aspergillosis. the pk parameters in lung samples were systematically higher than in serum. after multipl ...201727889253
cutaneous invasive aspergillosis in a patient with glioblastoma receiving long-term temozolomide and corticosteroid therapy.glioblastoma is an aggressive brain tumor that requires multidisciplinary treatment including adjuvant radiotherapy, chemotherapy, and adjunct corticosteroids. temozolomide is a commonly used chemotherapy drug and frequently causes lymphocytopenia. we describe the case of a 67-year-old woman with cutaneous invasive aspergillosis who had received long-term temozolomide and corticosteroid therapy for glioblastoma. she presented with multiple indurations, erythema, and purpura, some of which produc ...201727889247
a fungus-specific protein domain is essential for rasa-mediated morphogenetic signaling in aspergillus fumigatus.ras proteins function as conserved regulators of eukaryotic growth and differentiation and are essential signaling proteins orchestrating virulence in pathogenic fungi. here, we report the identification of a novel n-terminal domain of the rasa protein in the filamentous fungus aspergillus fumigatus. whereas this domain is absent in ras homologs of higher eukaryotes, the n-terminal extension is conserved among fungi and is characterized by a short string of two to eight amino acids terminating i ...201727921081
identification and evaluation of novel drug targets against the human fungal pathogen aspergillus fumigatus with elaboration on the possible role of rna-binding protein.aspergillus fumigatus is an airborne opportunistic fungal pathogen that can cause fatal infections in immunocompromised patients. although the current anti-fungal therapies are relatively efficient, some issues such as drug toxicity, drug interactions, and the emergence of drug-resistant fungi have promoted the intense research toward finding the novel drug targets.201728000798
fungal allergens in a saxophonist who had never smoked with allergic bronchopulmonary aspergillosis previously diagnosed as copd. 201727996950
production of the immunosuppressant cyclosporin a by a new soil isolate, aspergillus fumigatus, in submerged culture.cyclosporin a (cya) has received meticulous attention owing to its immunosuppressive and biological activities. in this study, a soil isolate, capable of producing cya, was named zag1 strain and identified as aspergillus fumigatus based on macroscopic and microscopic characteristics, 18s rdna sequence, and phylogenetic characteristic analysis. to maximize the production of cya, the fungal culture was grown under various fermentation conditions including selection of the cultivation medium, agita ...201727995310
beneficial effects of omalizumab therapy in allergic bronchopulmonary aspergillosis: a synthesis review of published literature.omalizumab, a humanized mab that binds to ige, has been an effective therapy for patients with severe allergic asthma; however, there are few clinical trials examining the efficacy of omalizumab in patients with allergic bronchopulmonary aspergillosis (abpa) except some case reports. to assess the clinical and immunological effects of omalizumab in abpa patients, we made a synthesis review of 102 cases from 30 published literature, analyzed the effects of omalizumab therapy in abpa and conducted ...201727993289
epidemiology of invasive aspergillosis and azole resistance in patients with acute leukaemia: the sepia study.invasive aspergillosis (ia) is a serious hazard to high-risk haematological patients. there are increasing reports of azole-resistant aspergillus spp. this study assessed the epidemiology of ia and azole-resistant aspergillus spp. in patients with acute leukaemia in germany. a prospective multicentre cohort study was performed in german haematology/oncology centres. the incidence of probable and proven aspergillosis according to the revised eortc/msg criteria was assessed for all patients with a ...201727989379
fungicides induced triazole-resistance in aspergillus fumigatus associated with mutations of tr46/y121f/t289a and its appearance in agricultural fields.azole resistance in aspergillus fumigatus is a growing public health problem. the sources of this resistance have been gained much attention. the present study was conducted to assess if resistant strain of a. fumigatus and its associated mutations in cyp51a could be induced by triazole fungicides and whether the resistant strain of a. fumigatus exist in agricultural fields. the results indicated that the resistance in a. fumigatus with mutations of tr46/y121f/t289a, a284t, g448s and p222q could ...201727987450
erg4a and erg4b are required for conidiation and azole resistance via regulation of ergosterol biosynthesis in aspergillus fumigatus.ergosterol, a fungus-specific sterol enriched in cell plasma membranes, is an effective antifungal drug target. however, current knowledge of the ergosterol biosynthesis process in the saprophytic human fungal pathogen aspergillus fumigatus remains limited. in this study, we found that two endoplasmic reticulum-localized sterol c-24 reductases encoded by both erg4a and erg4b homologs are required to catalyze the reaction during the final step of ergosterol biosynthesis. loss of one homolog of er ...201727986720
enhancing melting curve analysis for the discrimination of loop-mediated isothermal amplification products from four pathogenic molds: use of inorganic pyrophosphatase and its effect in reducing the variance in melting temperature values.loop-mediated isothermal amplification (lamp) is widely used for differentiating causative agents in infectious diseases. melting curve analysis (mca) in conjunction with the lamp method reduces both the labor required to conduct an assay and contamination of the products. however, two factors influence the melting temperature (tm) of lamp products: an inconsistent concentration of mg(2+) ion due to the precipitation of mg2p2o7, and the guanine-cytosine (gc) content of the starting dumbbell-like ...201727984058
influence of platelet-rich plasma on the immune response of human monocyte-derived dendritic cells and macrophages stimulated with aspergillus fumigatus.dendritic cells (dcs) and macrophages (mφ) are critical for protection against pathogenic fungi including aspergillus fumigatus. to analyze the role of platelets in the innate immune response, human dcs and mφs were challenged with a. fumigatus in presence or absence of human platelet rich plasma (prp). gene expression analyses and functional investigations were performed. a systems biological approach was used for initial modelling of the dc - a. fumigatus interaction. dcs in a quiescent state ...201727965080
disseminated aspergillosis in an immunocompetent patient with detectable bis(methylthio)gliotoxin and negative galactomannan.disseminated invasive aspergillosis is an exceptional finding in immunocompetent hosts. as in immunocompromised patients, it has high mortality rates. early diagnostic methods are required in order to properly manage the patient. bis(methylthio)gliotoxin (bmgt) is a novel biomarker, useful in onco-hematological patients.201727939578
the er-mitochondria encounter structure contributes to hyphal growth, mitochondrial morphology and virulence of the pathogenic mold aspergillus fumigatus.aspergillus fumigatus is an opportunistic fungal pathogen and the primary causative species of invasive aspergillosis, a systemic disease associated with high mortality rates. treatment of invasive fungal infection relies on a very limited number of antifungal drug classes. in order to extend the spectrum of antifungal drugs novel target structures have to be identified. the er-mitochondria encounter structure (ermes), a recently discovered tether that links mitochondria and endoplasmic reticulu ...201727939177
assessment of multi-contaminant exposure in a cancer treatment center: a 2-year monitoring of molds, mycotoxins, endotoxins, and glucans in bioaerosols.indoor air quality in health care facilities is a major public health concern, particularly for immunocompromised patients who may be exposed to microbiological contaminants such as molds, mycotoxins, endotoxins, and (1,3)-ß-d-glucans. over 2 years, bioaerosols were collected on a monthly basis in a cancer treatment center (centre f. baclesse, normandy, france), characterized from areas where there was no any particular air treatment. results showed the complexity of mycoflora in bioaerosols wit ...201728012082
interspecies discrimination of a. fumigatus and siblings a. lentulus and a. felis of the aspergillus section fumigati using the aspergenius(®) assay.the aspergenius(®) assay detects several aspergillus species and the a. fumigatus cyp51a mutations tr34/l98h/t289a/y121f that are associated with azole resistance. we evaluated its contribution in identifying a. lentulus and a. felis, 2 rare but intrinsically azole-resistant sibling species within the aspergillus section fumigati. identification of these species with conventional culture techniques is difficult and time-consuming. the assay was tested on (i) 2 a. lentulus and a. felis strains ob ...201728007314
xyloglucan breakdown by endo-xyloglucanase family 74 from aspergillus fumigatus.xyloglucan is the most abundant hemicellulose in primary walls of spermatophytes except for grasses. xyloglucan-degrading enzymes are important in lignocellulosic biomass hydrolysis because they remove xyloglucan, which is abundant in monocot-derived biomass. fungal genomes encode numerous xyloglucanase genes, belonging to at least six glycoside hydrolase (gh) families. gh74 endo-xyloglucanases cleave xyloglucan backbones with unsubstituted glucose at the -1 subsite or prefer xylosyl-substituted ...201728013403
indole-3-acetic acid/diol based ph-sensitive biological macromolecule for antibacterial, antifungal and antioxidant applications.indole-3-acetic acid (iaa)/diol based ph-sensitive biopolymeric hydrogels with tunable biological properties (cytotoxicity, anti-oxidant and anti-fungal) have been synthesized via condensation polymerization. the present study focused on the synthesis of heterocyclic hydrogel using citric acid (ca), indole-3-acetic acid (iaa) and diethylene glycol (deg) by condensation polymerization. the hydrogels revealed a ph-sensitive swelling behaviour, with increased swelling in acidic media, then turns to ...201727888010
modifications to the composition of the hyphal outer layer of aspergillus fumigatus modulates huvec proteins related to inflammatory and stress responses.aspergillus fumigatus, the main etiologic agent causing invasive aspergillosis, can induce an inflammatory response and a prothrombotic phenotype upon contact with human umbilical vein endothelial cells (huvecs). however, the fungal molecules involved in this endothelial response remain unknown. a. fumigatus hyphae produce an extracellular matrix composed of galactomannan, galactosaminogalactan and α-(1,3)-glucan. in this study, we investigated the consequences of ugm1 gene deletion in a. fumiga ...201727321585
functional reconstitution of a fungal natural product gene cluster by advanced genome editing.filamentous fungi produce varieties of natural products even in a strain dependent manner. however, the genetic basis of chemical speciation between strains is still widely unknown. one example is trypacidin, a natural product of the opportunistic human pathogen aspergillus fumigatus, which is not produced among different isolates. combining computational analysis with targeted gene editing, we could link a single nucleotide insertion in the polyketide synthase of the trypacidin biosynthetic pat ...201727611015
30 years of battling the cell wall.in aspergillus fumigatus, like in other pathogenic fungi, the cell wall is essential for fungal growth as well as for resisting environmental stresses such as phagocytic killing. most of the chemical analyses undertaken on the cell wall of a. fumigatus are focused on the mycelial cell wall because it is the vegetative stage of the fungus. however, the cell walls of the mycelium and conidium (which is the infective propagule) are different especially at the level of the surface layer, which plays ...201727609562
quantification of a. fumigatus-specific cd154+ t-cells-preanalytic considerations.fungal specific cd154(+) t-cells have been described as a biomarker in invasive aspergillosis. the influence of sample storage on the detection of these cells was assessed. six-hour delay prior to pbmc isolation is associated with an 18% decrease of cell viability and alterations of the cellular composition of the sample. this results in 87% reduction of cd154(+) a. fumigatus specific cells due to reduced assay sensitivity and increased background values in unstimulated samples. if prompt cell m ...201727486216
aspergillus pseudomembranous tracheobronchitis in an immunocompetent individual: a diagnostic conundrum with therapeutic challenge.aspergillus tracheobronchitis is an extremely uncommon manifestation of aspergillus infection. most of the cases described in the literature are in the immunosuppressed individuals and is almost uniformly fatal. immunocompetent individuals do manifest the disease, but the disease if diagnosed early can be appropriately treated and thus can be life-saving. here, we describe a similar case which was diagnosed only at autopsy.201727625454
performance evaluation of multiplex pcr including aspergillus-not so simple!multiplex pcrs have been designed for including species other than aspergillus fumigatus for the diagnosis of invasive aspergillosis, such as microarrays, liquid-phase array, and electrospray-ionization mass spectrometry (pcr/esi ms). these methods are based on the selection of multiple primers to amplify different species with the specificity checked by hybridization to a probe or by base composition of the amplicon for the pcr/esi ms. when testing complex samples such as respiratory specimens, ...201727664168
are allergic fungal rhinosinusitis and allergic bronchopulmonary aspergillosis lifelong conditions?aspergillus fumigatus can cause several allergic disorders including aspergillus-sensitized asthma, allergic bronchopulmonary aspergillosis (abpa), and allergic fungal rhinosinusitis (afrs). abpa is an immunological pulmonary disorder caused by allergic reactions mounted against antigens of a. fumigatus colonizing the airways of patients with asthma (and cystic fibrosis). allergic bronchopulmonary mycosis is an allergic fungal airway disease caused by thermotolerant fungi other than a. fumigatus ...201727601608
allergic bronchopulmonary aspergillosis in asthma. 201727599560
modified release itraconazole amorphous solid dispersion to treat aspergillus fumigatus: importance of the animal model selection.previously, modified release itraconazole in the form of a melt-extruded amorphous solid dispersion based on a ph dependent enteric polymer combined with hydrophilic additives (hme-itz), exhibited improved in vitro dissolution properties. these properties agreed with pharmacokinetic results in rats showing high and sustained itraconazole (itz) systemic levels. the objective of the present study was to better understand the best choice of rodent model for evaluating the pharmacokinetic and effica ...201727645428
a rare case of peripheral vascular graft infection by aspergillus fumigatus and review of the literature.we present an unusual case of a 74-year-old woman who presented with a pseudoaneurysm at the site of a previous prosthetic femoro-popliteal bypass graft and underwent an urgent repair with pseudoaneurysm excision and extra-anatomic placement of an autologous venous graft. microbiology examination revealed aspergillus fumigatus infection of the graft, which is a very rare condition. long-term antifungal medication has been administrated with positive outcome. only a few cases have been reported i ...201727659379
could we predict airborne aspergillus contamination during construction work?aspergillus fumigatus is a major opportunistic pathogen causing nosocomial infection. hospital outbreaks of invasive aspergillosis have been associated with demolition and building construction. this study was designed to examine the impact of meteorologic factors and different periods of work on outdoor fungal airborne concentrations.201727665035
genome-wide transcriptome analysis of aspergillus fumigatus exposed to osmotic stress reveals regulators of osmotic and cell wall stresses that are saka(hog1) and mpkc dependent.invasive aspergillosis is predominantly caused by aspergillus fumigatus, and adaptations to stresses experienced within the human host are a prerequisite for the survival and virulence strategies of the pathogen. the central signal transduction pathway operating during hyperosmotic stress is the high osmolarity glycerol mitogen-activated protein kinase cascade. a. fumigatus mpkc and saka, orthologues of the saccharomyces cerevisiae hog1p, constitute the primary regulator of the hyperosmotic stre ...201727706915
home environment as a source of life-threatening azole-resistant aspergillus fumigatus in immunocompromised patients.a case of fatal aspergillosis due to a tr46/y121f/t289a azole-resistant aspergillus fumigatus is reported. environmental investigations at the patient's residence led to the recovery of tr46/y121f/t289a isolates, genotypically indistinguishable from the clinical isolate, supporting for the first time the direct role of household as potential source of azole-resistant invasive aspergillosis.201727682064
case series of omalizumab for allergic bronchopulmonary aspergillosis in cystic fibrosis patients.allergic bronchopulmonary aspergillosis (abpa) affects up to 15% of patients with cystic fibrosis (cf). corticosteroids are used as first-line therapy, but relapse and adverse effects commonly occur. case reports have suggested the efficacy of the anti-ige recombinant humanized monoclonal antibody omalizumab. a retrospective multicenter observational french study retrieved 32 cf patients (11 children and 21 adults) who have received omalizumab for more than 3 months in the context of abpa. clini ...201727717223
predicting aspergillus fumigatus exposure from composting facilities using a dispersion model: a conditional calibration and validation.bioaerosols are released in elevated quantities from composting facilities and are associated with negative health effects, although dose-response relationships are unclear. exposure levels are difficult to quantify as established sampling methods are costly, time-consuming and current data provide limited temporal and spatial information. confidence in dispersion model outputs in this context would be advantageous to provide a more detailed exposure assessment. we present the calibration and va ...201727745825
spectrophotometric reading of eucast antifungal susceptibility testing of aspergillus fumigatus.given the increasing number of antifungal drugs and the emergence of resistant aspergillus isolates, objective, automated and high-throughput antifungal susceptibility testing is important. the eucast e.def 9.3 reference method for mic determination of aspergillus species relies on visual reading. spectrophotometric reading was not adopted because of concern that non-uniform filamentous growth might lead to unreliable and non-reproducible results. we therefore evaluated spectrophotometric readin ...201727793736
genotyping of aspergillus fumigatus reveals compartmentalization of genotypes in disseminated disease after invasive pulmonary aspergillosis. 201727795351
prospective biomarker screening for diagnosis of invasive aspergillosis in high-risk pediatric patients.combined biomarker screening is increasingly used to diagnose invasive aspergillosis (ia) in high-risk patients. in adults, the combination of galactomannan (gm) and fungal dna detection has proven to be beneficial in the diagnosis of ia. data in purely pediatric cohorts are scarce. here, we monitored 39 children shortly before and after allogeneic stem cell transplantation twice weekly by use of a commercial gm enzyme-linked immunosorbent assay (elisa) and a pcr assay based on amplification of ...201727795339
a study of the potential release of bioaerosols from containers as a result of reduced frequency residual waste collections.microorganisms have the potential to grow within waste containers if waste is stored for longer periods as a result of an extended residual waste collection cycle. release of microorganisms as bioaerosols during waste collection and processing may be an occupational risk to workers within the industry. there may be many constituents of the bioaerosol that may be of concern, however, there are currently only workplace exposure limits proposed for endotoxin (90eum(-3)). a field-scale trial was est ...201727810739
diagnosis of invasive pulmonary aspergillosis.culturing strains from clinical samples is the main method to diagnose invasive pulmonary aspergillosis. detecting the galactomannan antigen in serum samples is an auxiliary examination. the goal of this study was to determine the frequency with which aspergillus fumigatus was cultured in clinical samples taken from patients hospitalized in the the infant jesus teaching hospital in warsaw, poland, in the period of 2013-2014. specimens from the respiratory tract and blood were cultured for mycolo ...201727826887
evaluation of mic strip isavuconazole test for susceptibility testing of wild-type and non-wild-type aspergillus fumigatus isolates.we evaluated the mic strip isavuconazole test against eucast e.def 9.3 by using 40 wild-type and 39 cyp51a mutant aspergillus fumigatus strains. the strip full inhibition endpoint (fie) and 80% growth inhibition endpoint were determined by two independent readers, reader 1 (r1) and r2. the essential (within ±0, ±1, and ±2 twofold dilutions) and categorical agreements were best with the fie (for r1/r2, 42%/41%, 75%/73%, and 90%/89% for essential agreement, and 91.1%/92.4% categorical agreement, w ...201727799223
screening and characterization of a non-cyp51a mutation in an aspergillus fumigatus cox10 strain conferring azole resistance.the rapid and global emergence of azole resistance in the human pathogen aspergillus fumigatus has drawn attention. thus, a thorough understanding of its mechanisms of drug resistance requires extensive exploration. in this study, we found that the loss of the putative calcium-dependent protein-encoding gene alga causes an increased frequency of azole-resistant a. fumigatus isolates. in contrast to previously identified azole-resistant isolates related to cyp51a mutations, only one isolate carri ...201727799210
aspergillosis and the role of mucins in cystic fibrosis.the prevalence of aspergillosis in cf patients has until recently been underestimated, but increasing evidence suggests that it may play an important role in the progression of cf lung disease. in healthy airways, aspergillus fumigatus can be efficiently removed from the lung by mechanisms such as mucociliary clearance and cough. however, these mechanisms are defective in cf, allowing pathogens such as a. fumigatus to germinate and establish chronic infections within the airways. the precise mea ...201727870227
vayg1 is required for microsclerotium formation and melanin production in verticillium dahliae.the fungus verticillium dahliae causes vascular wilt disease on many plant species, including economically important crop and ornamental plants worldwide. it produces darkly pigmented resting structures known as microsclerotia, which are able to survive for up to 14years in soil, and represent one of the defining characteristics of this species. the pigment produced in v. dahliae is dihydroxynaphthalene (dhn)-melanin, a form of melanin common among fungi and named so for the intermediary of this ...201727866941
multicenter study of method-dependent epidemiological cutoff values for detection of resistance in candida spp. and aspergillus spp. to amphotericin b and echinocandins for the etest agar diffusion method.method-dependent etest epidemiological cutoff values (ecvs) are not available for susceptibility testing of either candida or aspergillus species with amphotericin b or echinocandins. in addition, reference caspofungin mics for candida spp. are unreliable. candida and aspergillus species wild-type (wt) etest mic distributions (microorganisms in a species-drug combination with no detectable phenotypic resistance) were established for 4,341 candida albicans, 113 c. dubliniensis, 1,683 c. glabrata ...201727799206
evasion of neutrophil extracellular traps by respiratory pathogens.the release of neutrophil extracellular traps (nets) is a major immune mechanism intended to capture pathogens. these histone- and protease-coated dna structures are released by neutrophils in response to a variety of stimuli, including respiratory pathogens, and have been identified in the airways of patients with respiratory infection, cystic fibrosis, acute lung injury, primary graft dysfunction, and chronic obstructive pulmonary disease. net production has been demonstrated in the lungs of m ...201727854516
two degradation strategies for overcoming the recalcitrance of natural lignocellulosic xylan by polysaccharides-binding gh10 and gh11 xylanases of filamentous fungi.the recalcitrance of lignocellulose forms a strong barrier for the bioconversion of lignocellulosic biomass in chemical or biofuel industries. filamentous fungi are major plant biomass decomposer, and capable of forming all the required enzymes. here, they characterized the gh10 and gh11 endo-xylanases and a ce1 acetyl-xylan esterase (axe1) from a superior biomass-degrading strain, aspergillus fumigatus z5, and examined how they interact in xylan degradation. cellulose-binding (cbm1) domain inhi ...201727878934
are cystic fibrosis aspergillus fumigatus isolates different? intermicrobial interactions with pseudomonas.pseudomonas aeruginosa and aspergillus fumigatus are the leading bacterial and fungal pathogens in cystic fibrosis (cf). we have shown that af biofilms are susceptible to pseudomonas, particularly cf phenotypes. those studies were performed with a reference virulent non-cf aspergillus. pseudomonas resident in cf airways undergo profound genetic and phenotypic adaptations to the abnormal environment. studies have also indicated aspergillus from cf patients have unexpected profiles of antifungal s ...201727822731
nimesulide inhibits pathogenic fungi: pge2-dependent mechanisms.certain non-steroidal anti-inflammatory drugs can inhibit fungal growth, fungal prostaglandin e2 production, and enzyme activation. this study aims to investigate the antifungal effect of nimesulide against pathogenic filamentous fungi and yeast. the experiments detailed below were also designed to investigate whether the action is dependent on e2 fungal prostaglandins. our data showed that nimesulide exhibited potent antifungal activity, mainly against trichophyton mentagrophytes (atcc 9533) an ...201727866353
pulmonary immune responses against aspergillus fumigatus are characterized by high frequencies of il-17 producing t-cells.in healthy individuals and in patients with invasive aspergillosis, aspergillus-specific t-cells in peripheral blood display mainly a thelper1 phenotype. although in other fungal infections thelper17 immunity is important, it was suggested that in aspergillus infection thelper17 cells do not play a role or may even be detrimental.201727838522
molecular detection of resistance to azole components.fungal infections have increased significantly in the last few years, and their outcomes are in part complicated by the emergence of antifungal drug-resistant pathogens. together with candida species, the mould aspergillus fumigatus is one of the most prevalent organisms to cause invasive fungal disease. the molecular detection of (tri)azole resistance in both candida and aspergillus species may represent a useful means of monitoring the incidence of clinical isolates with antifungal resistance- ...201727837519
visualization of aspergillus fumigatus biofilms with scanning electron microscopy and variable pressure-scanning electron microscopy: a comparison of processing techniques.aspergillus fumigatus biofilms consist of a three-dimensional network of cellular hyphae and extracellular matrix. they are involved in infections of immune-compromised individuals, particularly those with cystic fibrosis. these structures are associated with persistence of infection, resistance to host immunity, and antimicrobial resistance. thorough understanding of structure and function is imperative in the design of therapeutic drugs. optimization of processing parameters, including aldehyd ...201727836634
microbiota of high-pressure-processed serrano ham investigated by culture-dependent and culture-independent methods.the microbiota of serrano dry-cured ham of different chemical composition, subjected or not to high-pressure processing (hpp), was investigated using culture-dependent and culture-independent methods. microbial counts were submitted to analysis of variance with physicochemical parameters (aw, nacl concentration, salt-in-lean ratio and intramuscular fat content) or hpp as main effects. in untreated hams, physicochemical parameters significantly affected counts of aerobic mesophiles, psychrotrophs ...201727835773
mutation on gly115 and tyr205 of the cyclic dipeptide c2-prenyltransferase ftmpt1 increases its catalytic activity toward hydroxynaphthalenes.the fungal cyclic dipeptide prenyltransferase ftmpt1 from aspergillus fumigatus catalyzes a regular c2-prenylation of brevianamide f (cyclo-l-trp-l-pro) and is involved in the biosynthesis of a number of biologically active natural products including tryprostatins, spirotryprostatins, verruculogen, and fumitremorgins. ftmpt1, like other members of the dimethylallyltryptophan synthase superfamily, was shown to have high substrate promiscuity for tryptophan-containing cyclic dipeptides and a few o ...201727833992
characterization of aspergillus fumigatus isolates from air and surfaces of the international space station.one mission of the microbial observatory experiments on the international space station (iss) is to examine the traits and diversity of fungal isolates to gain a better understanding of how fungi may adapt to microgravity environments and how this may affect interactions with humans in a closed habitat. here, we report an initial characterization of two isolates, issft-021 and if1sw-f4, of aspergillus fumigatus collected from the iss and a comparison to the experimentally established clinical is ...201727830189
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