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retrospective analysis of the microbiological spectrum of pneumonia in turkish patients with lung cancer.the spectrum of pulmonary infections in patients with lung cancer is wide, and tools for target-oriented infection control measures are necessary. in this retrospective study we report the microbiological spectrum of pneumonia (based on the results of sputum culture) in a case series of turkish patients with lung malignancies.201627095942
phylogenetic and structural analysis of polyketide synthases in aspergilli.polyketide synthases (pkss) of aspergillus species are multidomain and multifunctional megaenzymes that play an important role in the synthesis of diverse polyketide compounds. putative pks protein sequences from aspergillus species representing medically, agriculturally, and industrially important aspergillus species were chosen and screened for in silico studies. six candidate aspergillus species, aspergillus fumigatus af293, aspergillus flavus nrrl3357, aspergillus niger cbs 513.88, aspergill ...201627199544
cryopreserved ex vivo-expanded allogeneic myeloid progenitor cell product protects neutropenic mice from a lethal fungal infection.severe neutropenia induced by chemotherapy or conditioning for hematopoietic cell transplantation often results in morbidity and mortality due to infection by opportunistic pathogens. a system has been developed to generate ex vivo-expanded mouse myeloid progenitor cells (mmpcs) that produce functional neutrophils in vivo upon transplantation in a pathogen challenge model. it has previously been demonstrated that transplantation of large numbers of freshly isolated myeloid progenitors from a sin ...201625812169
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
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
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
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
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
human neutrophils are primed by chemoattractant gradients for blocking the growth of aspergillus fumigatus.the contribution of human neutrophils to the protection against fungal infections by aspergillus fumigatus is essential but not fully understood. whereas healthy people can inhale spores of a. fumigatus without developing disease, neutropenic patients and those receiving immunosuppressive drugs have a higher incidence of invasive fungal infections. to study the role of neutrophils in protection against a. fumigatus infections, we developed an in vitro assay in which the interactions between huma ...201626272935
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
impact of urban air pollution on the allergenicity of aspergillus fumigatus conidia: outdoor exposure study supported by laboratory experiments.understanding the chemical interactions of common allergens in urban environments may help to decipher the general increase in susceptibility to allergies observed in recent decades. in this study, asexual conidia of the allergenic mold aspergillus fumigatus were exposed to air pollution under natural (ambient) and controlled (laboratory) conditions. the allergenic activity was measured using two immunoassays and supported by a protein mass spectrometry analysis. the allergenicity of the conidia ...201626410711
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
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
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
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
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
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
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
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
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
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
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
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
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
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
quaternary ammonium biocides as antimicrobial agents protecting historical wood and brick.quaternary ammonium compounds (qacs) are widely used in disinfection of water, surfaces and instruments as well as in textile, leather and food industries because of their relatively low toxicity, broad antimicrobial spectrum, non-volatility and chemical stability. due to these advantages, qacs are also used in restoration and can be applied on historical material. the aim of this study was to determine the usefulness of biocides based on quaternary ammonium salts and containing various excipien ...201626629794
regulation of mitochondrial inner membrane fusion: divergent evolution with similar solutions?continuous mitochondrial fusion and fission define the dynamic shape of mitochondria. one essential player of mitochondrial fusion is the conserved inner membrane dynamin-like gtpase mgm1/opa1. limited proteolysis of this protein has been proposed as a mechanism to separate and subsequently eliminate dysfunctional parts from the mitochondrial network. here, i briefly summarize our current knowledge about the underlying proteolytic processing steps in mammals, baker's yeast, schizosaccharomyces p ...201626613727
mycologic endocrinology.the interactions of fungi and chemical messenger molecules, hormones or pheromones, are addressed in this chapter. these interactions include mammalian fungal pathogens, also plant pathogens, or non-pathogenic fungi, which can result in functional responses in receptor- or non-receptor-mediated fashions. endogenous ligands in the fungi have been demonstrated to be important for mating in a number of systems. mammalian hormones have been demonstrated to have stimulatory or inhibitory effects on g ...201626589227
blood basophil activation is a reliable biomarker of allergic bronchopulmonary aspergillosis in cystic fibrosis.the diagnosis of cystic fibrosis (cf) patients with allergic bronchopulmonary aspergillosis (abpa) is clinically challenging, due to the absence of an objective biological test. since blood basophils play a major role in allergic responses, we hypothesised that changes in their surface activation pattern discriminate between cf patients with and without abpa.we conducted a prospective longitudinal study (stanford cohort) comparing basophil activation test cd203c levels by flow cytometry before a ...201626585435
zinc and manganese chelation by neutrophil s100a8/a9 (calprotectin) limits extracellular aspergillus fumigatus hyphal growth and corneal infection.calprotectin, a heterodimer of s100a8 and s100a9, is an abundant neutrophil protein that possesses antimicrobial activity primarily because of its ability to chelate zinc and manganese. in the current study, we showed that neutrophils from calprotectin-deficient s100a9(-/-) mice have an impaired ability to inhibit aspergillus fumigatus hyphal growth in vitro and in infected corneas in a murine model of fungal keratitis; however, the ability to inhibit hyphal growth was restored in s100a9(-/-) mi ...201626582948
ptx3, a humoral pattern recognition molecule at the interface between microbe and matrix recognition.innate immunity consists of a cellular and a humoral arm. ptx3 is a fluid patter recognition molecule (prm) with antibody-like properties. gene targeted mice and genetic associations in humans suggest that ptx3 plays a non-redundant role in resistance against selected pathogens (e.g. aspergillus fumigatus, pseudomonas aeruginosa, uropathogenic escherichia coli) and in the regulation of inflammation. ptx3 acts as an extrinsic oncosuppressor by taming complement elicited tumor-promoting inflammati ...201626650391
diagnosis and management of aspergillosis in the netherlands: a national survey.a survey of diagnosis and treatment of invasive aspergillosis was conducted in eight university medical centers (umcs) and eight non-academic teaching hospitals in the netherlands. against a background of emerging azole resistance in aspergillus fumigatus routine resistance screening of clinical isolates was performed primarily in the umcs. azole resistance rates at the hospital level varied between 5% and 10%, although rates up to 30% were reported in high-risk wards. voriconazole remained firs ...201626648179
hydrogen peroxide-induced secondary necrosis in conidia of aspergillus fumigatus.aspergillus fumigatus conidia have been linked to severe aspergillosis in immunocompromised patients. recently, the cytotoxic effect of secondary metabolites from a. fumigatus conidia was reported. in the present work, a methodology used to detect cell death markers in fungal hyphae was adapted to study conidia cell death. additionally, the mechanism of h2o2-induced cell death was studied in a. fumigatus conidia for the first time. data presented in this work reveal that the h2o2-induced conidia ...201626639790
role of the mannose receptor during aspergillus fumigatus infection and interaction with dectin-1 in corneal epithelial cells.to investigate the expression and function of the mannose receptor (mr) and to explore its interaction with dectin-1 in human corneal epithelial cells (hcecs) exposed to aspergillus fumigatus.201626606296
mutant characterization and in vivo conditional repression identify aromatic amino acid biosynthesis to be essential for aspergillus fumigatus virulence.pathogenicity of the saprobe aspergillus fumigatus strictly depends on nutrient acquisition during infection, as fungal growth determines colonisation and invasion of a susceptible host. primary metabolism has to be considered as a valid target for antimycotic therapy, based on the fact that several fungal anabolic pathways are not conserved in higher eukaryotes. to test whether fungal proliferation during invasive aspergillosis relies on endogenous biosynthesis of aromatic amino acids, defined ...201626605426
trpe feedback mutants reveal roadblocks and conduits toward increasing secondary metabolism in aspergillus fumigatus.small peptides formed from non-ribosomal peptide synthetases (nrps) are bioactive molecules produced by many fungi including the genus aspergillus. a subset of nrps utilizes tryptophan and its precursor, the non-proteinogenic amino acid anthranilate, in synthesis of various metabolites such as aspergillus fumigatus fumiquinazolines (fqs) produced by the fmq gene cluster. the a. fumigatus genome contains two putative anthranilate synthases - a key enzyme in conversion of anthranilic acid to trypt ...201626701311
highly efficient crispr mutagenesis by microhomology-mediated end joining in aspergillus fumigatus.filamentous fungi have a dominant nonhomologous-end joining (nhej) dna repair pathway, which results in the majority of transformed progenies having random heterologous insertion mutagenesis. thus, lack of a versatile genome-editing tool prevents us from carrying out precise genome editing to explore the mechanism of pathogenesis. moreover, clinical isolates that have a wild-type ku80 background without any selection nutrition marker especially suffer from low homologous integration efficiency. ...201626701308
the spectrum of allergic fungal diseases of the upper and lower airways.fungi cause a wide spectrum of fungal diseases of the upper and lower airways. there are three main phyla involved in allergic fungal disease: (1) ascomycota (2) basidiomycota (3) zygomycota. allergic fungal rhinosinusitis (afrs) causes chronic rhinosinusitis symptoms and is caused predominantly by aspergillus fumigatus in india and bipolaris in the united states. the recommended treatment approach for afrs is surgical intervention and systemic steroids. allergic bronchopulmonary aspergillosis ( ...201626776889
in vivo veritas: aspergillus fumigatus proliferation and pathogenesis--conditionally speaking. 201626695225
azole resistance of aspergillus fumigatus in immunocompromised patients with invasive aspergillosis. 201626691166
azole resistance of aspergillus fumigatus in immunocompromised patients with invasive aspergillosis. 201626690934
multiple fungicide-driven alterations in azole-resistant aspergillus fumigatus, colombia, 2015. 201626690795
horizontal acquisition of toxic alkaloid synthesis in a clade of plant associated fungi.clavicipitaceae is a fungal group that comprises species that closely interact with plants as pathogens, parasites or symbionts. a key factor in these interactions is the ability of these fungi to synthesize toxic alkaloid compounds that contribute to the protection of the plant host against herbivores. some of these compounds such as ergot alkaloids are toxic to humans and have caused important epidemics throughout history. the gene clusters encoding the proteins responsible for the synthesis o ...201626688468
comparison of six aspergillus-specific igg assays for the diagnosis of chronic pulmonary aspergillosis (cpa).chronic pulmonary aspergillosis (cpa) is estimated to affect 3 million persons worldwide. aspergillus-specific igg is a key component in cpa diagnosis. we aimed to establish the optimal diagnostic cut offs for cpa and the comparative performance of six assays in this context.201626680697
detection of airway colonization by aspergillus fumigatus by use of electronic nose technology in patients with cystic fibrosis.currently, there is no noninvasive test that can reliably diagnose early invasive pulmonary aspergillosis (ia). an electronic nose (enose) can discriminate various lung diseases through an analysis of exhaled volatile organic compounds. we recently published a proof-of-principle study showing that patients with prolonged chemotherapy-induced neutropenia and ia have a distinct exhaled breath profile (or breathprint) that can be discriminated with an enose. an enose is cheap and noninvasive, and i ...201626677251
highly efficient and easy protease-mediated protein purification.as both research on and application of proteins are rarely focused on the resistance towards nonspecific proteases, this property remained widely unnoticed, in particular in terms of protein purification and related fields. in the present study, diverse aspects of protease-mediated protein purification (pmpp) were explored on the basis of the complementary proteases trypsin and proteinase k as well as the model proteins green fluorescent protein (gfp) from aequorea victoria, lipase a from candid ...201626671615
purification, biochemical characterization and structural modelling of alkali-stable β-1,4-xylan xylanohydrolase from aspergillus fumigatus r1 isolated from soil.aspergillus fumigatus r1 produced xylanase under submerged fermentation which degrades the complex hemicelluloses contained in agricultural substrates. xylanases have gained considerable attention because of their tremendous applications in industries. the purpose of our study was to purify xylanase and study its biochemical properties. we have predicted the secondary structure of purified xylanase and evaluated its active site residues and substrate binding sites based on the global and local s ...201626847222
three extracellular dipeptidyl peptidases found in aspergillus oryzae show varying substrate specificities.three extracellular dipeptidyl peptidase genes, dppb, dppe, and dppf, were unveiled by sequence analysis of the aspergillus oryzae genome. we investigated their differential enzymatic profiles, in order to gain an understanding of the diversity of these genes. the three dipeptidyl peptidases were expressed using aspergillus nidulans as the host. each recombinant enzyme was purified and subsequently characterized. the enzymes displayed similar optimum ph values, but optimum temperatures, ph stabi ...201626846741
aspergillus mediastinitis after cardiac surgery.mediastinitis is a serious complication after cardiac surgery. while bacteria are the more common pathogens, fungal infections are rare. in particular, several cases of postoperative aspergillus mediastinitis have been reported, the majority of which had an extremely poor outcome.201626845443
a novel inhibition elisa for the detection and monitoring of penicillium marneffei antigen in human serum.the thermally dimorphic fungus penicillium marneffei is a causative agent of penicilliosis marneffei, a disease considered to be an acquired immune deficiency syndrome (aids)-defining illness in southeast asia and southern china. we have developed an inhibition enzyme-linked immunosorbent assay (inh-elisa) incorporating the yeast phase specific mannoprotein-binding monoclonal antibody 4d1 for the detection of p. marneffei infection. in our sample set, the test detected antigenemia in all 45 (100 ...201626838686
dectin-1 controls tlr9 trafficking to phagosomes containing β-1,3 glucan.dectin-1 and tlr9 play distinct roles in the recognition and induction of innate immune responses to aspergillus fumigatus and candida albicans. dectin-1 is a receptor for the major fungal cell wall carbohydrate β-1,3 glucan that induces inflammatory cytokines and controls phagosomal maturation through spleen tyrosine kinase activation. tlr9 is an endosomal tlr that also modulates the inflammatory cytokine response to fungal pathogens. in this study, we demonstrate that β-1,3 glucan beads are su ...201626829985
identification of pseudomonas aeruginosa and aspergillus fumigatus mono- and co-cultures based on volatile biomarker combinations.volatile organic compound (voc) analysis in exhaled breath is proposed as a non-invasive method to detect respiratory infections in cystic fibrosis patients. since polymicrobial infections are common, we assessed whether we could distinguish pseudomonas aeruginosa and aspergillus fumigatus mono- and co-cultures using the voc emissions. we took headspace samples of p. aeruginosa, a. fumigatus and co-cultures at 16, 24 and 48 h after inoculation, in which vocs were identified by thermal desorption ...201626824272
the signal peptide peptidase sppa is involved in sterol regulatory element-binding protein cleavage and hypoxia adaptation in aspergillus nidulans.using forward genetics, we revealed that the signal peptide peptidase (spp) sppa, an aspartyl protease involved in regulated intramembrane proteolysis (rip), is essential for hypoxia adaptation in aspergillus nidulans, as well as hypoxia-sensitive mutant alleles of a sterol regulatory element-binding protein (srebp) srba and the dsc ubiquitin e3 ligase complex dsca-e. both null and dead activity [d337a] mutants of sppa failed to grow in hypoxia, and the growth defect of δsppa was complemented by ...201626822492
molecular-based allergy diagnosis of allergic bronchopulmonary aspergillosis in aspergillus fumigatus-sensitized japanese patients. 201626817858
epidemiology and molecular mechanisms of antifungal resistance in candida and aspergillus.the significant increase in the use of antifungal agents, both for the treatment of candidiasis and invasive aspergillosis and as azole fungicides in agricultural crop protection has resulted in the emergence of resistant clinical isolates, particularly to triazoles and echinocandins. notably, among isolates that were primarily sensitive to fluconazole such as candida parapsilosis and candida tropicalis have witnessed an emerging resistance development. also for echinocandins, the occurrence of ...201626810669
effect of media modified to mimic cystic fibrosis sputum on the susceptibility of aspergillus fumigatus, and the frequency of resistance at one center.studies of cystic fibrosis (cf) patient exacerbations attributed topseudomonas aeruginosainfection have indicated a lack of correlation of outcome within vitrosusceptibility results. one explanation is that the media used for testing do not mimic the airway milieu, resulting in incorrect conclusions. therefore, media have been devised to mimic cf sputum.aspergillus fumigatusis the leading fungal pathogen in cf, and susceptibility testing is also used to decide therapeutic choices. we assessed wh ...201626810647
sequential inactivation of gliotoxin by the s-methyltransferase tmta.the epipolythiodioxopiperazine (etp) gliotoxin mediates toxicity via its reactive thiol groups and thereby contributes to virulence of the human pathogenic fungus aspergillus fumigatus. self-intoxication of the mold is prevented either by reversible oxidation of reduced gliotoxin or by irreversible conversion to bis(methylthio)gliotoxin. the latter is produced by the s-methyltransferase tmta and attenuates etp biosynthesis. here, we report the crystal structure of tmta in complex with s-(5'-aden ...201626808594
immunopet/mr imaging allows specific detection of aspergillus fumigatus lung infection in vivo.invasive pulmonary aspergillosis (ipa) is a life-threatening lung disease caused by the fungus aspergillus fumigatus, and is a leading cause of invasive fungal infection-related mortality and morbidity in patients with hematological malignancies and bone marrow transplants. we developed and tested a novel probe for noninvasive detection of a. fumigatus lung infection based on antibody-guided positron emission tomography and magnetic resonance (immunopet/mr) imaging. administration of a [(64)cu]d ...201626787852
exploration of sulfur assimilation of aspergillus fumigatus reveals biosynthesis of sulfur-containing amino acids as a virulence determinant.fungal infections are of major relevance due to the increased numbers of immunocompromised patients, frequently delayed diagnosis, and limited therapeutics. to date, the growth and nutritional requirements of fungi during infection, which are relevant for invasion of the host, are poorly understood. this is particularly true for invasive pulmonary aspergillosis, as so far, sources of (macro)elements that are exploited during infection have been identified to only a limited extent. here, we have ...201626787716
occurrence of mycotoxins and yeasts and moulds identification in corn silages in tropical climate.this study was aimed to identify yeasts and moulds as well as to detect mycotoxin in corn silages in southern minas gerais, brazil.201626787003
cd203c in patients with cystic fibrosis and allergy to aspergillus fumigatus. 201626782973
chronic aspergillus fumigatus colonization of the pediatric cystic fibrosis airway is common and may be associated with a more rapid decline in lung function.filamentous fungi are commonly isolated from the respiratory tract of cf patients, but their clinical significance is uncertain and the reported incidence variable. we report on the degree of aspergillus fumigatus airway colonization in a tertiary pediatric cf cohort, evaluate the sensitivity of routine clinical sampling at detecting a. fumigatus, and compare lung function of a. fumigatus-colonized and non-colonized children.we carried out an 8-year retrospective cohort analysis using local data ...201626782645
de-repression of csp-1 activates adaptive responses to antifungal azoles.antifungal azoles are the major drugs that are used to treat fungal infections. this study found that in response to antifungal azole stress, neurospora crassa could activate the transcriptional responses of many genes and increase azole resistance by reducing the level of conidial separation 1 (csp-1), a global transcription repressor, at azole-responsive genes. the expression of csp-1 was directly activated by the transcription factors wc-1 and wc-2. upon ketoconazole (ktc) stress, the transcr ...201626781458
late aspergilloma of a renal allograft without need for operative management: a case report and review of the literature.aspergillus infection localized to the renal allograft is a rare and potentially life-threatening infection and typically requires a combination of operative and medical management. we report the case of a renal allograft aspergilloma in a renal transplant patient presenting 2 years post transplant, successfully managed non-surgically. to our knowledge, this is the first report of a patient presenting with an allograft aspergilloma so long after transplantation and being successfully managed wit ...201626751414
aspergillus cell wall melanin blocks lc3-associated phagocytosis to promote pathogenicity.concealing pathogen-associated molecular patterns (pamps) is a principal strategy used by fungi to avoid immune recognition. surface exposure of pamps during germination can leave the pathogen vulnerable. accordingly, β-glucan surface exposure during aspergillus fumigatus germination activates an atg5-dependent autophagy pathway termed lc3-associated phagocytosis (lap), which promotes fungal killing. we found that lap activation also requires the genetic, biochemical or biological (germination) ...201626749442
aspergillus otitis in small animals--a retrospective study of 17 cases.aspergillus spp. are saprophytic opportunistic fungal organisms and are a common cause of otomycosis in humans. although there have been case reports of aspergillus otitis externa in dogs, to the best of the authors' knowledge, this is the first retrospective case series describing aspergillus otitis in dogs and cats.201626748885
identification and characterization of haemofungin, a novel antifungal compound that inhibits the final step of haem biosynthesis.during recent decades, the number of invasive fungal infections among immunosuppressed patients has increased significantly, whereas the number of effective systemic antifungal drugs remains low and unsatisfactory. the aim of this study was to characterize a novel antifungal compound, cw-8/haemofungin, which we previously identified in a screen for compounds affecting fungal cell wall integrity.201626747101
serological diagnosis of allergic bronchopulmonary mycosis: progress and challenges.prompt diagnosis of allergic bronchopulmonary mycosis (abpm) is an important clinical issue in preventing irreversible lung damage. therefore, a good serological marker for the diagnosis of abpm is desired in clinical practice. the measurement of ige antibody to crude aspergillus fumigatus allergen is considered the first step in screening asthmatic patients for allergic bronchopulmonary aspergillosis (abpa). however, presence of ige to a. fumigatus does not always indicate genuine sensitization ...201626740298
the iron-responsive microsomal proteome of aspergillus fumigatus.aspergillus fumigatus is an opportunistic fungal pathogen. siderophore biosynthesis and iron acquisition are essential for virulence. yet, limited data exist with respect to the adaptive nature of the fungal microsomal proteome under iron-limiting growth conditions, as encountered during host infection. here, we demonstrate that under siderophore biosynthetic conditions--significantly elevated fusarinine c (fsc) and triacetylfusarinine c (tafc) production (p<0.0001), extensive microsomal proteom ...201626739764
draft genome sequence of the pathogenic filamentous fungus aspergillus lentulus ifm 54703t.aspergillus lentulus, a sibling species of aspergillus fumigatus, has been reported as a causative agent of aspergillosis, and exhibited low susceptibility to azole. here, we present the draft genome sequence of a. lentulus strain ifm 54703(t) for the first time.201626769945
aspergillus fumigatus produces two arabinofuranosidases from glycosyl hydrolase family 62: comparative properties of the recombinant enzymes.the genes of two α-l-arabinofuranosidases (abfi and ii) from family gh 62 have been identified in the genome of aspergillus fumigatus wmo. both genes have been expressed in pichia pastoris and the enzymes have been purified and characterized. abfi is composed of 999 bp, does not contain introns and codes for a protein (abfi) of 332 amino acid residues. abfii has 1246 bp, including an intron of 51 bp; the protein abfii has 396 amino acid residues; it includes a family 1 carbohydrate-binding modul ...201626769705
immunomodulatory effect of mesenchymal stem cells on the immune response of macrophages stimulated by aspergillus fumigatus conidia.mesenchymal stem cells (mscs) are known to exert potent immunosuppression and anti-inflammatory effects. there is growing interest in their use for immunotherapy for controlling inflammation as well as acute organ injury. however, there are few reports regarding msc's immunomodulatory effects in the settings of fungal infection. in this study, we attempted to examine the immunomodulatory effects of mscs in response to aspergillus fumigatus we measured the cytokine response of murine mscs on the ...201626768375
cyp51a-based mechanism of azole resistance in aspergillus fumigatus: illustration by a new 3d structural model of aspergillus fumigatus cyp51a protein.mutations of cyp51a protein (cytochrome p450 14-α sterol demethylase) play a central role in the azole resistance of aspergillus fumigatus the available structural models of cyp51a protein ofa. fumigatus are built based on that of homo sapiens and that of mycobacterium tuberculosis, of which the amino acid homology is only 38% and 29% compared with cyp51a protein ofa. fumigatus, respectively. in the present study, we constructed a new 3d structural model ofa. fumigatus cyp51a protein based on a ...201626768370
aspergillus fumigatus promotes t helper type 2 responses through thymic stromal lymphopoietin production by human corneal epithelial cells.fungal keratitis is a major cause of blindness. to understand the mechanism of both innate and adaptive immunity in corneal infection is of great significance in the treatment and prevention of fungal keratitis. our previous study concerned innate immunity. here, we explored the potential role of thymic stromal lymphopoietin (tslp) in adaptive immunity of fungal keratitis.201626759304
human neutrophils use different mechanisms to kill aspergillus fumigatus conidia and hyphae: evidence from phagocyte defects.neutrophils are known to play a pivotal role in the host defense against aspergillus infections. this is illustrated by the prevalence of aspergillus infections in patients with neutropenia or phagocyte functional defects, such as chronic granulomatous disease. however, the mechanisms by which human neutrophils recognize and kill aspergillus are poorly understood. in this work, we have studied in detail which neutrophil functions, including neutrophil extracellular trap (net) formation, are invo ...201626718340
purification and characterization of polygalacturonase from aspergillus fumigatus mtcc 2584 and elucidating its application in retting of crotalaria juncea fiber.polygalacturonases represents an important member of pectinases group of enzymes with diverse industrial applications and is widely distributed among fungi, bacteria, yeasts, plants and some plant parasitic nematodes. an endo-polygalacturonase from a new fungal source aspergillus fumigatus mtcc 2584 was produced under solid-state fermentation conditions and was purified simply by acetone precipitation and gel-filtration chromatography technique. the approximate molecular weight of the purified p ...201628330273
enzymatic production of glucosamine and chitooligosaccharides using newly isolated exo-β-d-glucosaminidase having transglycosylation activity.exochitosanase secreting fungus (a. fumigatus iit-004) was isolated from fish waste using 1 % (w/v) chitosan as sole carbon source after multistage screening. chitosan-dependent exochitosanase enzyme production (6 iu ml(-1)) in log phase of growth (chitosan utilization rate 0.11 g g(-1) cell h(-1)) was observed for aspergillus fumigatus in chitosan minimal salt medium and there was no enzyme production in glucose medium. enzyme production was found to be extracellular and subjected to purificati ...201628330083
in vitro resistance of aspergillus fumigatus to azole farm fungicide.azole resistance in aspergillus fumigatus is mainly due to a point mutation in the 14α-sterol demethylase (cyp51a) gene, which encodes the target of azole fungicides. moreover, overexpression of cyp51b or multidrug resistance (mdr) gene is supposedly related to the mechanism of azole resistance in a. fumigatus. in this study, we tried to induce resistance to tetraconazole, an azole fungicide, in strains of a. fumigatus from a farm and then investigated mutation and expression of their cyp51a, cy ...201626711232
tolerance to silver of an aspergillus fumigatus strain able to grow on cyanide containing wastes.we studied the strategy of an aspergillus fumigatus strain able to grow on metal cyanide wastes to cope with silver. the tolerance test revealed that the minimum inhibitory concentration of ag(i) was 6mm. in 1mm agno3 aqueous solution the fungus was able to reduce and sequestrate silver into the cell in the form of nanoparticles as evidenced by the change in color of the biomass and electron microscopy observations. extracellular silver nanoparticle production also occurred in the filtrate solut ...201626705888
high-resolution ultrasound including contrast-enhanced ultrasound (ceus) for the detection of gas formation during aspergillus fumigatus infection in mice.a. fumigatus infections represent a major threat for patients with a suppressed immune system. early diagnosis is of importance for a favorable outcome but appears to be difficult due to limited diagnostic procedures. here we investigated the sensitivity of high-resolution ultrasound (hru) for the detection of a. fumigatus infection in the liver.201625741669
assessment of probiotic, antifungal and cholesterol lowering properties of pediococcus pentosaceus kcc-23 isolated from italian ryegrass.lactic acid bacteria (lab) are important for the processing of various food products. although genetically modified organisms have contributed to improvements in various food products, there are some limitations. thus, the discovery of wild strains from natural sources must be considered as the most suitable approach for identifying new lab. therefore, we planned to isolate and characterise the lab from italian ryegrass forage and evaluate their biological potential.201625655225
purification, immobilization, and biochemical characterization of l-arginine deiminase from thermophilic aspergillus fumigatus kj434941: anticancer activity in vitro.l-arginine deiminase (adi) has a powerful anticancer activity against various tumors, via arginine depletion, arresting the cell cycle at g1 phase. however, the current clinically tried bacterial adi displayed a higher antigenicity and lower thermal stability. thus, our objective was to purify and characterize this enzyme from thermophilic fungi, to explore its catalytic and antigenic properties for therapeutic uses. adi was purified from thermophilic aspergillus fumigatus kj434941 to its electr ...201625582958
prevalence of allergic fungal rhinosinusitis among patients with chronic rhinosinusitis with or without nasal polyposis who underwent endonasal sinus surgery in northwestern turkey.this study aims to evaluate the prevalence of allergic fungal rhinosinusitis in chronic rhinosinusitis patients in the northwest of turkey.201625513868
heat shock protein 90 (hsp90): a novel antifungal target against aspergillus fumigatus.invasive aspergillosis is a life-threatening and difficult to treat infection in immunosuppressed patients. the efficacy of current anti-aspergillus therapies, targeting the cell wall or membrane, is limited by toxicity (polyenes), fungistatic activity and some level of basal resistance (echinocandins), or the emergence of acquired resistance (triazoles). the heat shock protein 90 (hsp90) is a conserved molecular chaperone involved in the rapid development of antifungal resistance in the yeast c ...201625243616
histidine biosynthesis plays a crucial role in metal homeostasis and virulence of aspergillus fumigatus.aspergillus fumigatus is the most prevalent airborne fungal pathogen causing invasive fungal infections in immunosuppressed individuals. the histidine biosynthetic pathway is found in bacteria, archaebacteria, lower eukaryotes, and plants, but is absent in mammals. here we demonstrate that deletion of the gene encoding imidazoleglycerol-phosphate dehydratase (hisb) in a. fumigatus causes (i) histidine auxotrophy, (ii) decreased resistance to both starvation and excess of various heavy metals, in ...201626854126
orbital apex syndrome caused by invasive aspergillosis as an adverse effect of systemic chemotherapy for metastatic colorectal cancer: a case report.continuous therapy with cytotoxic drugs suppresses humoral immune function and may result in local infection. we present a case of orbital apex syndrome caused by aspergillus infection during chemotherapy for metastatic colorectal cancer. a 74-year-old man with colorectal liver metastases under long-term continuous systemic chemotherapy presented with painful, progressive orbital apex syndrome. magnetic resonance imaging disclosed a small enhancing lesion around the right ethmoid sinus. we initi ...201626851046
t7-rna polymerase dependent rnai system in aspergillus fumigatus: a proof of concept study.an rnai system based on t7 rna polymerase (trnap) was designed and examined in aspergillus fumigatus. this system consists of two elements; an inducible t7rnap expressing cassette and an ama1-based episomal rnai plasmid. these constructs were transformed into the a. fumigatus protoplasts and the efficiency of this system was tested in downregulation of alb1 gene. upon the induction of t7rnap expression, the recombinant t7rnap was able to recognize t7 promoters, which were located on the episomal ...201626850443
aspergillus fumigatus cala binds to integrin α5β1 and mediates host cell invasion.aspergillus fumigatus is an opportunistic fungal pathogen that invades pulmonary epithelial cells and vascular endothelial cells by inducing its own endocytosis, but the mechanism by which this process occurs is poorly understood. here, we show that the thaumatin-like protein cala is expressed on the surface of the a. fumigatus cell wall, where it mediates invasion of epithelial and endothelial cells. cala induces endocytosis in part by interacting with integrin α5β1 on host cells. in corticoste ...201627841851
microbial colonization and lung function in adolescents with cystic fibrosis.with intensified antibiotic therapy and longer survival, patients with cystic fibrosis (cf) are colonized with a more complex pattern of bacteria and fungi. however, the clinical relevance of these emerging pathogens for lung function remains poorly defined. the aim of this study was to assess the association of bacterial and fungal colonization patterns with lung function in adolescent patients with cf. microbial colonization patterns and lung function parameters were assessed in 770 adolescent ...201626856310
deciphering the counterplay of aspergillus fumigatus infection and host inflammation by evolutionary games on graphs.microbial invaders are ubiquitously present and pose the constant risk of infections that are opposed by various defence mechanisms of the human immune system. a tight regulation of the immune response ensures clearance of microbial invaders and concomitantly limits host damage that is crucial for host viability. to investigate the counterplay of infection and inflammation, we simulated the invasion of the human-pathogenic fungus aspergillus fumigatus in lung alveoli by evolutionary games on gra ...201627291424
pharmacokinetics and concentration-dependent efficacy of isavuconazole for treatment of experimental invasive pulmonary aspergillosis.we studied the pharmacokinetics and efficacy of the broad-spectrum triazole isavuconazole for the treatment of experimental invasive pulmonary aspergillosis (ipa) in persistently neutropenic rabbits. treatment started 24 h after endotracheal administration of aspergillus fumigatus inoculum; study subjects included rabbits receiving orally administered prodrug isavuconazonium sulfate (bal8557) equivalent to active moiety isavuconazole (isa; bal4815) at 20 (isa20), 40 (isa40), and 60 (isa60) mg/kg ...201626883703
chaetomium atrobrunneum and aspergillus fumigatus in multiple tracheal aspirates: copathogens or symbiosis.chaetomium atrobrunneum has never been reported to be associated with pneumonia. we report the isolation of c. atrobrunneum and aspergillus fumigatus from a chinese elderly patient with fatal pneumonia. branched, long, and septate hyphae were observed in potassium hydroxide preparations and gram-stained smears, and confluent c. atrobrunneum growth and a few a. fumigatus colonies were found in tracheal aspirates (nine separate occasions). these isolates were identified by conventional morphologic ...201626880338
clinical characteristics of patients with aspergillus species isolation from respiratory samples: comparison of chronic pulmonary aspergillosis and colonization.with advancements in anti-fungal drugs, it has become more important to correctly diagnose chronic pulmonary aspergillosis (cpa); however, it is not easy to distinguish cpa from colonization when aspergillus species are isolated from respiratory samples. the aim of the study was to clarify the particular clinical characteristics of patients with cpa vs. those with colonization.201626879478
invasive pulmonary aspergillosis in organ transplants--focus on lung transplants.infections with filamentous fungi are common in transplant recipients. the risk for aspergillosis and other invasive pulmonary mycosis (ipm) is high in patients undergoing stem cell and lung transplantations. the mortality rates range from 20% to 60% and depend on a number of risk factors. the typical manifestations of ipm are lung infiltrates, consolidations, and fungal tracheobronchitis. the most common infectious agent is aspergillus fumigatus. infections caused by non-aspergillus molds are m ...201626879476
mitogen activated protein kinases saka(hog1) and mpkc collaborate for aspergillus fumigatus virulence.here, we investigated which stress responses were influenced by the mpkc and saka mitogen-activated protein kinases of the high-osmolarity glycerol (hog) pathway in the fungal pathogen aspergillus fumigatus. the δsaka and the double δmpkc δsaka mutants were more sensitive to osmotic and oxidative stresses, and to cell wall damaging agents. both mpkc::gfp and saka::gfp translocated to the nucleus upon osmotic stress and cell wall damage, with saka::gfp showing a quicker response. the phosphorylat ...201626878695
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