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stimulation with lysates of aspergillus terreus, candida krusei and rhizopus oryzae maximizes cross-reactivity of anti-fungal t cells.invasive fungal diseases caused by filamentous fungi and yeasts are significant causes of morbidity and mortality in immunosuppressed hematology patients. we previously published a method to expand aspergillus fumigatus-specific t cells for clinical cell therapy. in the present study, we investigated expansion of t cells specific for other fungal pathogens and creation of a broadly reactive panfungal t-cell product.201626552765
tet-on, or tet-off, that is the question: advanced conditional gene expression in aspergillus.in aspergillus, controlled gene expression is often achieved using the reverse tetracycline-controlled transactivator (rtta) dependent tet-on system, whereby transcription is activated in a titratable manner by addition of the tetracycline derivative doxycycline. the complementary tet-off system utilises the tetracycline-controlled transactivator (tta) component to quantitatively reduce gene expression. in this study, we utilised a synthetic biological approach to engineer highly optimised tet-o ...201626555930
molecular characterization of a voriconazole-resistant, posaconazole-susceptible aspergillus fumigatus isolate in a lung transplant recipient in the united states.molecular characterization of cyp51a from the azole-resistant aspergillus fumigatus isolate 50593 from a lung transplant patient showed y121f/t289a changes coupled with a 46-bp tandem repeat (tr46) on the promoter, whereas cyp51a from the pretherapy isolate, a. fumigatus 47381, showed no changes. this is the first reported case of a. fumigatus azole resistance due to y121f/t289a/tr46 in the united states, suggesting that multiple mutational alterations of cyp51a resulting in high-level azole res ...201626574014
utility of ige (total and aspergillus fumigatus specific) in monitoring for response and exacerbations in allergic bronchopulmonary aspergillosis.the role of total and specific ige in monitoring treatment responses in allergic bronchopulmonary aspergillosis (abpa) remains poorly studied. here in, we evaluate the utility of total and aspergillus fumigatus specific ige in the follow-up of abpa. eighty-one consecutive treatment-naïve patients of abpa (acute stage) with pulmonary infiltrates and bronchiectasis underwent measurement of total and a. fumigatus specific ige at baseline, after 8 weeks of glucocorticoid therapy, and during exacerba ...201626575791
group 2 innate lymphoid cells mediate ozone-induced airway inflammation and hyperresponsiveness in mice.asthmatic patients are highly susceptible to air pollution and in particular to the effects of ozone (o3) inhalation, but the underlying mechanisms remain unclear.201626282284
serum opsonin ficolin-a enhances host-fungal interactions and modulates cytokine expression from human monocyte-derived macrophages and neutrophils following aspergillus fumigatus challenge.invasive aspergillosis is a devastating invasive fungal disease associated with a high mortality rate in the immunocompromised, such as leukaemia patients, transplant patients and those with hiv/aids. the rodent serum orthologue of human l-ficolin, ficolin-a, can bind to and opsonize aspergillus fumigatus, the pathogen that causes invasive aspergillosis, and may participate in fungal defence. using human monocyte-derived macrophages and neutrophils isolated from healthy donors, we investigated c ...201626337048
aspergillus fumigatus cap59-like protein a is involved in α1,3-mannosylation of gpi-anchors.glycosylphosphatidylinositol (gpi) attaches a variety of eukaryotic proteins to the outer leaflet of the plasma membrane. in fungi, these proteins may also be transferred to the cell wall, to which they are covalently linked via a remnant of the gpi-anchor. they play crucial physiological roles in cell-cell interactions, adhesion or cell wall biogenesis. the biosynthesis of gpi-anchors in the endoplasmic reticulum, their transfer to proteins, early remodelling and transport to the golgi apparatu ...201626369907
the basophil surface marker cd203c identifies aspergillus species sensitization in patients with cystic fibrosis.colonization by aspergillus fumigatus in patients with cystic fibrosis (cf) can cause a fumigatus sensitization and/or allergic bronchopulmonary aspergillosis (abpa), which affects pulmonary function and clinical outcomes. recent studies show that specific allergens upregulate the surface-expressed basophil marker cd203c in sensitized subjects, a response that can be readily measured by using flow cytometry.201626388311
novel antimicrobial superporous cross-linked chitosan/pyromellitimide benzoyl thiourea hydrogels.in this work, chitosan (cs) was cross-linked with different amounts of pyromellitimide benzoyl thiourea moieties. the structure of the cross-linked cs was confirmed by elemental analyses, ftir and (1)h- nmr spectroscopy. the cross-linking process proceeds via reacting of the amino groups of cs with the isothiocyanate groups of the n,n'-bis [4-(isothiocyanate carbonyl)phenyl] pyromellitimide cross-linker. the amount of the cross-linker was varied with respect to cs to produce four new pyromelliti ...201626388182
first detection of tr34 l98h and tr46 y121f t289a cyp51 mutations in aspergillus fumigatus isolates in the united states.azole resistance in aspergillus fumigatus is an increasing problem. the tr34 l98h and tr46 y121f t289a mutations that can occur in patients without previous azole exposure have been reported in europe, asia, the middle east, africa, and australia. here, we report the detection of both the tr34 l98h and tr46 y121f t289a mutations in confirmed a. fumigatus isolates collected in institutions in the united states. these mutations, other mutations known to cause azole resistance, and azole mics are r ...201626491179
azole resistance in aspergillus fumigatus: can we retain the clinical use of mold-active antifungal azoles?azole resistance in aspergillus fumigatus has emerged as a global health problem. although the number of cases of azole-resistant aspergillosis is still limited, resistance mechanisms continue to emerge, thereby threatening the role of the azole class in the management of diseases caused by aspergillus. the majority of cases of azole-resistant disease are due to resistant a. fumigatus originating from the environment. patient management is difficult due to the absence of patient risk factors, de ...201626486705
quantitative proteomics reveals the mechanism and consequence of gliotoxin-mediated dysregulation of the methionine cycle in aspergillus niger.gliotoxin (gt) is a redox-active metabolite, produced by aspergillus fumigatus, which inhibits the growth of other fungi. here we demonstrate how aspergillus niger responds to gt exposure. quantitative proteomics revealed that gt dysregulated the abundance of 378 proteins including those involved in methionine metabolism and induced de novo abundance of two s-adenosylmethionine (sam)-dependent methyltransferases. increased abundance of enzymes s-adenosylhomocysteinase (p=0.0018) required for hom ...201626498071
ulcerative pseudomembranous tracheobronchitis caused by aspergillus fumigatus. 201626497417
elevated il-33 expression is associated with pediatric eosinophilic esophagitis, and exogenous il-33 promotes eosinophilic esophagitis development in mice.we tested whether the t helper (th) type 2 (th2) cell agonist and allergenic ligand il-33 was associated with eosinophilic esophagitis (eoe) development in a pediatric cohort and whether il-33 protein could induce disease symptoms in mice. biopsies from eoe patients or controls were used to measure il-33 mrna and protein expression. increased expression of il-33 mrna was found in the esophageal mucosa in eoe. il-33 protein was detected in cells negative for cd45, mast cells, and epithelial cell ...201626514775
phosphoinositide 3-kinase-δ regulates fungus-induced allergic lung inflammation through endoplasmic reticulum stress.sensitisation with aspergillus fumigatus (af) is known to be associated with severe allergic lung inflammation, but the mechanism remains to be clarified. phosphoinositide 3-kinase (pi3k)-δ and endoplasmic reticulum (er) stress are suggested to be involved in steroid-resistant lung inflammation. we aimed to elucidate the role of pi3k-δ and its relationship with er stress in fungus-induced allergic lung inflammation.201626543090
etiological analysis of fungal keratitis and rapid identification of predominant fungal pathogens.fungal keratitis is a worldwide-distributed refractory and potentially blinding ocular infection caused by various fungi. it is necessary to investigate the etiological and epidemiological characteristics of this disease and establish a rapid and specific pathogenic identification method. here, we isolated and identified fungal pathogens of 275 patients with presumed fungal keratitis from jilin province, china, and conducted statistical analyses of epidemiological information. the positive rate ...201626446032
gliotoxin--bane or boon?gliotoxin (gt) is the most important epidithiodioxopiperazine (etp)-type fungal toxin. gt was originally isolated from trichoderma species as an antibiotic substance involved in biological control of plant pathogenic fungi. a few isolates of gt-producing trichoderma virens are commercially marketed for biological control and widely used in agriculture. furthermore, gt is long known as an immunosuppressive agent and also reported to have anti-tumour properties. however, recent publications sugges ...201626443473
pseudallescheria boydii with aspergillus fumigatus and aspergillus terreus in a critically ill hematopoietic stem cell recipient with ards.pseudallescheria boydii is a fungal organism known to affect immunocompromised patients. this organism is known to cause, in severe cases, invasive infection of various organs such as the central nervous, cardiovascular, and respiratory systems. we report an unusual case of pulmonary p. boydii pneumonia in an immunocompromised critically ill patient with a co-infection of aspergillus fumigatus and aspergillus terreus with ards. this case highlights the importance of a high index of suspicion for ...201626455910
ecophysiology of environmental aspergillus fumigatus and comparison with clinical strains on gliotoxin production and elastase activity.the aim of this manuscript was to study the influence of water activity (aw ) and ph in the ecophysiological behaviour of aspergillus fumigatus strains at human body temperature. in addition, gliotoxin production and enzymatic ability among environmental (n = 2) and clinical (n = 5) strains were compared. ecophysiological study of environmental strains was performed on agar silage incubated at 37°c, studying the interaction at eight aw levels (0·8, 0·85, 0·9, 0·92, 0·94, 0·96, 0·98 and 0·99) and ...201626551056
human invariant natural killer t cells possess immune-modulating functions during aspergillus infection.aspergillus fumigatus is the most common cause for invasive fungal infections, a disease associated with high mortality in immune-compromised patients. cd1d-restricted invariant natural killer t (inkt) cells compose a small subset of t cells known to impact the immune response toward various infectious pathogens. to investigate the role of human inkt cells during a. fumigatus infection, we studied their activation as determined by cd69 expression and cytokine production in response to distinct f ...201626483428
pathogen gene expression profiling during infection using a nanostring ncounter platform.nanostring ncounter is a recently developed platform that can make direct multiplexed measurement of gene expression using color-coded probe pairs (geiss et al., nat biotechnol 26(3):317-325, 2008; malkov et al., bmc res notes 2:80, 2009). we have found that this platform is uniquely suitable for quantification of pathogen gene expression during infection, where pathogen rna comprises a tiny portion of total rna isolated from the infected tissue. here, we describe a protocol that we have success ...201626483015
role of aspergillus fumigatus in triggering protease-activated receptor-2 in airway epithelial cells and skewing the cells toward a t-helper 2 bias.aspergillus fumigatus (af) infection and sensitization are common and promote th2 disease in individuals with asthma. innate immune responses of bronchial epithelial cells are now known to play a key role in determination of t cell responses upon encounter with inhaled pathogens. we have recently shown that extracts of af suppress jak-stat signaling in epithelial cells and thus may promote th2 bias. to elucidate the impact of af on human bronchial epithelial cells, we tested the hypothesis that ...201626072921
use of principal factor analysis to generate a corn silage fermentative quality index to rank well- or poorly preserved forages.to investigate corn silage fermentative quality, a principal factor analysis was carried out on a database consisting of 196 corn silages sampled from the core, lateral and apical parts of silo feed-out face and characterised by 36 variables. eleven principal factor components (pcs) were retained and interpreted. two pcs were related to chemical and digestibility variables; four pcs were characterised by end-products associated with clostridia, heterolactic, homolactic or aerobic fermentations; ...201626010065
malignant fungal infection of the cavernous sinus: case report.intracranial spread of fungal infection is a life-threatening condition that usually affects immunocompromised patients. here the authors present a case of biopsy-proven aspergillus fumigatus infection of the paranasal sinuses in an immunocompetent patient with documented spread to the orbit, cavernous sinus, and petrous apex despite medical antifungal treatment. as a life-saving treatment, cavernous sinus resection with external carotid artery-middle cerebral artery bypass was performed. the au ...201626315007
redundant synthesis of a conidial polyketide by two distinct secondary metabolite clusters in aspergillus fumigatus.filamentous fungi are renowned for the production of bioactive secondary metabolites. typically, one distinct metabolite is generated from a specific secondary metabolite cluster. here, we characterize the newly described trypacidin (tpc) cluster in the opportunistic human pathogen aspergillus fumigatus. we find that this cluster as well as the previously characterized endocrocin (enc) cluster both contribute to the production of the spore metabolite endocrocin. whereas trypacidin is eliminated ...201626242966
thermotolerant and mesophylic fungi from sugarcane bagasse and their prospection for biomass-degrading enzyme production.nineteen fungi and seven yeast strains were isolated from sugarcane bagasse piles from an alcohol plant located at brazilian cerrado and identified up to species level on the basis of the gene sequencing of 5.8s-its and 26s ribosomal dna regions. four species were identified: kluyveromyces marxianus, aspergillus niger, aspergillus sydowii and aspergillus fumigatus, and the isolates were screened for the production of key enzymes in the saccharification of lignocellulosic material. among them, th ...201726413077
acute invasive pulmonary aspergillosis, shortly after occupational exposure to polluted muddy water, in a previously healthy subject.invasive pulmonary aspergillosis (ipa) predominantly occurs in severely neutropenic immunocompromised subjects. the occurrence of acute ipa after brief but massive exposure to aspergillus conidia in previously healthy subjects has been documented, although only six such cases have been reported. the diagnosis was delayed in all six of the affected patients, five of whom died. we report the case of a 50-year-old hiv-negative male, a water pipeline maintenance worker, who presented with acute-onse ...201726578140
profile and morphology of fungal aerosols characterized by field emission scanning electron microscopy (fesem).fungal aerosols consist of spores and fragments with diverse array of morphologies; however, the size, shape, and origin of the constituents require further characterization. in this study, we characterize the profile of aerosols generated from aspergillus fumigatus, a. versicolor, and penicillium chrysogenum grown for 8 weeks on gypsum boards. fungal particles were aerosolized at 12 and 20 l min(-1) using the fungal spore source strength tester (fssst) and the stami particle generator (spg). co ...201726855468
facing the challenges of multiscale modelling of bacterial and fungal pathogen-host interactions.recent and rapidly evolving progress on high-throughput measurement techniques and computational performance has led to the emergence of new disciplines, such as systems medicine and translational systems biology. at the core of these disciplines lies the desire to produce multiscale models: mathematical models that integrate multiple scales of biological organization, ranging from molecular, cellular and tissue models to organ, whole-organism and population scale models. using such models, hypo ...201726857943
surgical treatment of pulmonary aspergillosis: a single center experience.aspergillus fumigatus is a saprophytic fungus which colonizes in the cavitary lesions in the lungs. in our part of the world, where tuberculosis is endemic, the healed tubercular cavities form a good nidus for this fungus. the fungus forms a fungal ball or aspergilloma within the cavity, which erodes the walls of the cavity and causes hemoptysis by erosion of the bronchial vessels. hemoptysis is the main symptom. antifungal agents are not useful against the fungal ball. surgery in the form of lo ...201726933300
ecology of aspergillosis: insights into the pathogenic potency of aspergillus fumigatus and some other aspergillus species.fungi of the genus aspergillus are widespread in the environment. some aspergillus species, most commonly aspergillus fumigatus, may lead to a variety of allergic reactions and life-threatening systemic infections in humans. invasive aspergillosis occurs primarily in patients with severe immunodeficiency, and has dramatically increased in recent years. there are several factors at play that contribute to aspergillosis, including both fungus and host-related factors such as strain virulence and h ...201727273822
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
high frequency of pathogenic aspergillus species among nonsporulating moulds from respiratory tract samples.nonsporulating moulds (nsm) represent an identification challenge for clinical laboratories. data on the prevalence of pathogenic species among nsm are lacking. we prospectively investigated consecutive thermotolerant (36°c) clinical nsm isolates from respiratory tract samples. a total of 123 isolates were identified by dna sequencing and phenotypically characterized. of those, 13 (11%) were pathogenic species (aspergillus fumigatus, n = 10; a. flavus, n = 1; a. hiratsukae, n = 1; schizophyllum ...201727555561
phytochemical and cytogenetic characterization of centaurea solstitialis l. (asteraceae) from croatia.the cytogenetic characterization of centaurea solstitialis l. (asteraceae) showed a chromosome number of 2n = 16. karyotype is composed by four pairs of metacentric, two pairs of submetacentric and two pairs of subtelocentric chromosomes. physical mapping of two rdna probes revealed two loci of 35s and one locus of 5s rrna genes. chromomycin fluorochrome banding revealed that all rdna loci were gc rich. the genome size (2c-value) of 1.95 pg classes this species in the group of very small genomes ...201727552682
vitamin d supplementation decreases aspergillus fumigatus specific th2 responses in cf patients with aspergillus sensitization: a phase one open-label study.patients with cystic fibrosis (cf) complicated by allergic bronchopulmonary aspergillosis (abpa) are vitamin d deficient and in vitro treatment with 1,25 (oh)2 vitamin d3 of cd4+ cells from cf patients with abpa decreases aspergillus fumigatus(af)-induced th2 responses. this phase i clinical trial investigated the safety and effectiveness of daily vitamin d3 supplementation in cf patients with abpa to reduce allergic responses and abpa symptoms, and increase serum vitamin d levels.201727011794
pulmonary aspergillosis diagnosed by endoscopic ultrasound fine-needle aspiration.pulmonary aspergillosis generally occurs in patients with prolonged neutropenia or immunosupression. definitive diagnosis depends on the demonstration of the organism in tissue, as positive culture result from sputum, needle biopsy, or bronchoalveolar lavage fluid. even though endoscopic ultrasound (eus) fine needle aspiration (fna) of paraesophageal/mediastinal lesions has been used numerous times, this is the first case that reports an aspergilloma diagnosed by eus-fna, allowing us to reach a ...201726879169
a retrospective study of the epidemiology and clinical manifestation of invasive aspergillosis in a major tertiary care hospital in bahrain.limited data are available on the epidemiology, clinical manifestations and outcomes of patients with invasive aspergillosis in bahrain. this study was conducted retrospectively to determine the epidemiology of invasive aspergillosis and its risk factors, clinical presentation, underlying conditions, and outcomes over the past five years in a major hospital. the medical records of patients with positive aspergillus cultures admitted to a major tertiary care hospital in bahrain during 2009-2013 w ...201727033677
rbdb, a rhomboid protease critical for srebp activation and virulence in aspergillus fumigatus.srebp transcription factors play a critical role in fungal virulence; however, the mechanisms of sterol regulatory element binding protein (srebp) activation in pathogenic fungi remains ill-defined. screening of the neurospora crassa whole-genome deletion collection for genes involved in hypoxia responses identified a gene for an uncharacterized rhomboid protease homolog, rbdb, required for growth under hypoxic conditions. loss of rbdb in aspergillus fumigatus also inhibited growth under hypoxic ...201727303716
impaired calcineurin signaling in myeloid cells results in downregulation of pentraxin-3 and increased susceptibility to aspergillosis.treatment of post-transplant patients with immunosuppressive drugs targeting the calcineurin-nuclear factor of activated t cells (nfat) pathway, including cyclosporine a or tacrolimus, is commonly associated with a higher incidence of opportunistic infections, such as aspergillus fumigatus, which can lead to severe life-threatening conditions. a component of the a. fumigatus cell wall, β-glucan, is recognized by dendritic cells (dcs) via the dectin-1 receptor, triggering downstream signaling tha ...201727301880
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
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
role of aspergillus fumigatus-specific igg in diagnosis and monitoring treatment response in allergic bronchopulmonary aspergillosis.few studies have evaluated the utility of aspergillus fumigatus-specific igg in allergic bronchopulmonary aspergillosis (abpa). herein, we evaluate the role of specific igg in diagnosis and monitoring treatment response in abpa. forty-eight control subjects with a. fumigatus-associated asthma underwent a. fumigatus-specific igg measurements at baseline, while specific igg was assayed in 102 treatment-naïve subjects of abpa at baseline, after eight weeks of glucocorticoid therapy, and during exac ...201727523578
triazole resistance in aspergillus fumigatus isolates from patients with cystic fibrosis in italy.aspergillus fumigatus is frequently recovered from respiratory secretions of cystic fibrosis (cf) patients. azole resistance has been increasingly reported.201727356848
discovery of a new antifungal agent asp2397 using a silkworm model of aspergillus fumigatus infection.natural products are the major source of currently available drugs. however, screening natural product presents several challenges, including the time-consuming and labor-intensive steps required for the isolation of a drug from crude extracts as well as the differences between the activities of compounds in vitro and in vivo. to address these challenges, we used silkworm larvae infected with aspergillus fumigatus to screen a natural products library for potent drugs to treat invasive aspergillo ...201727577982
new phytochemical constituent and bioactivities of horwoodia dicksoniae and rumex cyprius.many plants growing in saudi arabia are used in folk medicine for treatment of several diseases.201727601844
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
chemical input reduction in the arabinoxylan and lignocellulose alkaline extraction and xylooligosaccharides production.lignocellulosic material breakdown by hydrolysis is an important step to open new perspectives for bioenergy and special foods production like prebiotic xylooligosaccharides. improvement of lignocellulose and arabinoxylan alkaline extraction from sugarcane bagasse and enzymatic hydrolysis were performed. treatments 1 (10% koh at 70°c), 3 (5% koh at 121°c) and zd method (24% koh at 35°c) showed solid lignocellulose recovery of respectively 75.2%, 74.2% and 73%. a range of 24.8-27% extracted mater ...201728063358
absent in vitro interaction between chloroquine and antifungals against aspergillus fumigatus. 201728062318
m-ficolin is present in aspergillus fumigatus infected lung and modulates epithelial cell immune responses elicited by fungal cell wall polysaccharides. 201728060571
two cases of non-cystic fibrosis (cf) bronchiectasis with allergic bronchopulmonary aspergillosis.allergic bronchopulmonary aspergillosis (abpa) is a complex hypersensitivity reaction in patients with asthma or cystic fibrosis (cf), which is associated with bronchi colonized by the fungus aspergillus species, most often aspergillus fumigatus. abpa is an important consideration for asthmatics that do not respond to asthma management or with recurrent chest infections and deteriorating lung function in children with cystic fibrosis. we present two cases of non cf bronchiectasis associated with ...201728053855
allergic bronchopulmonary mycosis caused by penicillium luteum.a 65-year-old japanese male had severe bronchial asthma had increased mold-containing sputum. serum total ige level had increased to 798 iu/ml and antigen-specific precipitating antibodies to p. luteum and p. notatum were present but not those reactive toward any species of aspergillus. chest computed tomography revealed central bronchiectasis and bronchial wall thickness. after antigen-specific provocation with 10 mg/ml of p. luteum, the patient developed asthma exacerbation, but not with a. fu ...201728053852
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
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
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
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
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
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
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
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
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
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
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
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