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prevalence and risk factors for allergic bronchopulmonary aspergillosis in indian children with cystic fibrosis.allergic bronchopulmonary aspergillosis (abpa) is a common complication in patients with cystic fibrosis. this cross-sectional study was planned to determine the prevalence and risk factors for abpa in indian children with cystic fibrosis.201424825267
distinct and complementary roles for aspergillus fumigatus-specific tr1 and foxp3+ regulatory t cells in humans and mice.unlike induced foxp3(+) regulatory t cells (foxp3(+) itreg) that have been shown to play an essential role in the development of protective immunity to the ubiquitous mold aspergillus fumigatus, type-(1)-regulatory t cells (tr1) cells have, thus far, not been implicated in this process. here, we evaluated the role of tr1 cells specific for an epitope derived from the cell wall glucanase crf-1 of a. fumigatus (crf-1/p41) in antifungal immunity. we identified crf-1/p41-specific latent-associated p ...201424820384
allergic aspergillosis and the antigens of aspergillus fumigatus.incidence of fungal infections has increased alarmingly in past few decades. of the fungal pathogens, the aspergillus fumigatus has been a major cause of allergic bronchopulmonary aspergillosis (abpa) which has five main stages--the acute, remission, exacerbation, glucocorticoid dependent and fibrotic stage. the diagnosis of abpa remains difficult due to its overlapping clinical and radiological features with tuberculosis and cystic fibrosis. from past few decades, the crude fractions of a. fumi ...201424818760
vaccination approaches against opportunistic fungal infections caused by aspergillus fumigatus.although innate immunity primarily combats systemic infections of opportunistic fungi such as aspergillus and candida spp., acquired and protective immunoreactions were observed long ago in animal trials following sublethal systemic infections caused by viable fungi or after challenging animals with inactivated fungal cells. based on these observations, fungal antigens should exist which mediate such protective immunoreactions and have in part already been identified. in this context, this revie ...201424818757
surface structure characterization of aspergillus fumigatus conidia mutated in the melanin synthesis pathway and their human cellular immune response.in aspergillus fumigatus, the conidial surface contains dihydroxynaphthalene (dhn)-melanin. six-clustered gene products have been identified that mediate sequential catalysis of dhn-melanin biosynthesis. melanin thus produced is known to be a virulence factor, protecting the fungus from the host defense mechanisms. in the present study, individual deletion of the genes involved in the initial three steps of melanin biosynthesis resulted in an altered conidial surface with masked surface rodlet l ...201424818666
iterative breakthrough invasive aspergillosis due to tr(34) /l98h azole-resistant aspergillus fumigatus and emericella sublata in a single hematopoietic stem cell transplant patient.we report 3 consecutive episodes of invasive aspergillosis in a single hematopoietic stem cell transplant patient successively attributed to tr(34) /l98h azole-resistant aspergillus fumigatus and to a first occurrence of invasive emericella sublata infection. this case illustrates potential selection of resistant molds during antifungal therapy in hematological patient.201424816170
the janus transcription factor hapx controls fungal adaptation to both iron starvation and iron excess.balance of physiological levels of iron is essential for every organism. in aspergillus fumigatus and other fungal pathogens, the transcription factor hapx mediates adaptation to iron limitation and consequently virulence by repressing iron consumption and activating iron uptake. here, we demonstrate that hapx is also essential for iron resistance via activating vacuolar iron storage. we identified hapx protein domains that are essential for hapx functions during either iron starvation or high-i ...201425092765
new case of azole-resistant aspergillus fumigatus due to tr46/y121f/t289a mutation in belgium. 201425086248
sexual reproduction of human fungal pathogens.we review here recent advances in our understanding of sexual reproduction in fungal pathogens that commonly infect humans, including candida albicans, cryptococcus neoformans/gattii, and aspergillus fumigatus. where appropriate or relevant, we introduce findings on other species associated with human infections. in particular, we focus on rapid advances involving genetic, genomic, and population genetic approaches that have reshaped our view of how fungal pathogens evolve. rather than being ase ...201425085958
identification of hypoxia-inducible target genes of aspergillus fumigatus by transcriptome analysis reveals cellular respiration as an important contributor to hypoxic survival.aspergillus fumigatus is an opportunistic, airborne pathogen that causes invasive aspergillosis in immunocompromised patients. during the infection process, a. fumigatus is challenged by hypoxic microenvironments occurring in inflammatory, necrotic tissue. to gain further insights into the adaptation mechanism, a. fumigatus was cultivated in an oxygen-controlled chemostat under hypoxic and normoxic conditions. transcriptome analysis revealed a significant increase in transcripts associated with ...201425084861
the involvement of the mid1/cch1/yvc1 calcium channels in aspergillus fumigatus virulence.aspergillus fumigatus is a major opportunistic pathogen and allergen of mammals. calcium homeostasis and signaling is essential for numerous biological processes and also influences a. fumigatus pathogenicity. the presented study characterized the function of the a. fumigatus homologues of three saccharomyces cerevisiae calcium channels, voltage-gated cch1, stretch-activated mid1 and vacuolar yvc1. the a. fumigatus calcium channels ccha, mida and yvca were regulated at transcriptional level by i ...201425083783
role of gliotoxin in the symbiotic and pathogenic interactions of trichoderma virens.using a gene disruption strategy, we generated mutants in the glip locus of the plant-beneficial fungus trichoderma virens that were no longer capable of producing gliotoxin. phenotypic assays demonstrated that the glip-disrupted mutants grew faster, were more sensitive to oxidative stress and exhibited a sparse colony edge compared with the wt strain. in a plate confrontation assay, the mutants deficient in gliotoxin production were ineffective as mycoparasites against the oomycete, pythium ult ...201425082950
sporadic distribution of prion-forming ability of sup35p from yeasts and fungi.sup35p of saccharomyces cerevisiae can form the [psi+] prion, an infectious amyloid in which the protein is largely inactive. the part of sup35p that forms the amyloid is the region normally involved in control of mrna turnover. the formation of [psi+] by sup35p's from other yeasts has been interpreted to imply that the prion-forming ability of sup35p is conserved in evolution, and thus of survival/fitness/evolutionary value to these organisms. we surveyed a larger number of yeast and fungal spe ...201425081567
incidence of cyp51 a key mutations in aspergillus fumigatus-a study on primary clinical samples of immunocompromised patients in the period of 1995-2013.as the incidence of azole resistance in aspergillus fumigatus is rising and the diagnosis of invasive aspergillosis (ia) in immunocompromised patients is rarely based on positive culture yield, we screened our aspergillus dna sample collection for the occurrence of azole resistance mediating cyp51 a key mutations. using two established, a modified and a novel polymerase chain reaction (pcr) assays followed by dna sequence analysis to detect the most frequent mutations in the a. fumigatus cyp51 a ...201425072733
the role of azoles in the management of azole-resistant aspergillosis: from the bench to the bedside.azole resistance is an emerging problem in aspergillus fumigatus and is associated with a high probability of treatment failure. an azole resistance mechanism typically decreases the activity of multiple azole compounds, depending on the mutation. as alternative treatment options are limited and in some isolates the minimum inhibitory concentration (mic) increases by only a few two-fold dilutions steps, we investigated if voriconazole and posaconazole have a role in treating azole-resistant aspe ...201425066814
rapid and specific detection of section fumigati and aspergillus fumigatus in human samples using a new multiplex real-time pcr.invasive aspergillosis is an opportunistic infection caused primarily by aspergillus fumigatus. however, other common fungal pathogens belonging to section fumigati are often misidentified as a. fumigatus. thus, we have developed a multiplex real-time pcr (qpcr) assay with primers and specific taqman probes based on internal transcribed spacer regions or bena gene to discriminate, in less than 3 h, species of section fumigati and, specifically, a. fumigatus. the multiplex qpcr showed a limit of ...201425063549
screening-based discovery of aspergillus fumigatus plant-type chitinase inhibitors.a limited therapeutic arsenal against increasing clinical disease due to aspergillus spp. necessitates urgent characterisation of new antifungal targets. here we describe the discovery of novel, low micromolar chemical inhibitors of aspergillus fumigatus family 18 plant-type chitinase a1 (afchia1) by high-throughput screening (hts). analysis of the binding mode by x-ray crystallography confirmed competitive inhibition and kinetic studies revealed two compounds with selectivity towards fungal pla ...201425063338
genome mining and functional genomics for siderophore production in aspergillus niger.iron is an essential metal for many organisms, but the biologically relevant form of iron is scarce because of rapid oxidation resulting in low solubility. simultaneously, excessive accumulation of iron is toxic. consequently, iron uptake is a highly controlled process. in most fungal species, siderophores play a central role in iron handling. siderophores are small iron-specific chelators that can be secreted to scavenge environmental iron or bind intracellular iron with high affinity. a second ...201425062661
opposed effects of enzymatic gliotoxin n- and s-methylations.gliotoxin (1), a virulence factor of the human pathogenic fungus aspergillus fumigatus, is the prototype of epipoly(thiodioxopiperazine) (etp) toxins. here we report the discovery and functional analysis of two methyl transferases (mts) that play crucial roles for etp toxicity. genome comparisons, knockouts, and in vitro enzyme studies identified a new s-adenosyl-l-methionine-dependent s-mt (tmta) that is, surprisingly, encoded outside the gli gene cluster. we found that tmta irreversibly inacti ...201425062268
inhaled corticosteroids and aspergillus fumigatus isolation in cystic fibrosis.aspergillus fumigatus isolation in cultures from respiratory specimens of patients with cystic fibrosis (cf) is quite common; however, the role of a. fumigatus as a pathogen and whether its presence is associated with progression of pulmonary disease remain unclear. we investigated the association between inhaled corticosteroids and the recovery of a. fumigatus by performing a retrospective cohort study of cf patients born between 1988 and 1996. the patients' medical records from their first vis ...201425056962
design, synthesis, antimicrobial evaluation and molecular docking studies of some new thiophene, pyrazole and pyridone derivatives bearing sulfisoxazole moiety.development of new antimicrobial agents is a good solution to overcome drug-resistance problems. in this context, new functionalized thiophene, acrylamide, arylhydrazone, pyrazole and pyridone derivatives bearing sulfisoxazole moiety were designed, synthesized and evaluated for their in vitro antibacterial and antifungal activities. among the synthesized compounds, thiophene 4d and 6-thioglucosylpyridone 17 displayed significant antibacterial activities against escherichia coli (mic, 0.007 μg/ml ...201425050881
coexpression and secretion of endoglucanase and phytase genes in lactobacillus reuteri.a multifunctional transgenic lactobacillus with probiotic characteristics and an ability to degrade β-glucan and phytic acid (phytate) was engineered to improve nutrient utilization, increase production performance and decrease digestive diseases in broiler chickens. the bacillus subtilis wl001 endoglucanase gene (celw) and aspergillus fumigatus wl002 phytase gene (phyw) mature peptide (phywm) were cloned into an expression vector with the lactate dehydrogenase promoter of lactobacillus casei an ...201425050780
ptx3 binds md-2 and promotes trif-dependent immune protection in aspergillosis.the long pentraxin 3 (ptx3) modulates different effector pathways involved in innate resistance to aspergillus fumigatus, including complement activation or promotion of phagocytosis by interacting with fcγrs. however, whether and how tlrs modulate ptx3 mediates antifungal resistance is not known. in this study, we demonstrate that ptx3 binds myeloid differentiation protein 2 (md-2) in vitro and exerts its protective antifungal activity in vivo through tlr4/md-2-mediated signaling. similar to tl ...201425049357
the role of interleukin-1 family members in the host defence against aspergillus fumigatus.the interleukin (il)-1 family consists of 11 members, which all play significant roles in regulating inflammatory responses in the host. il-1α and il-1β exert potent pro-inflammatory effects and are key players in the recruitment of neutrophils to the site of inflammation. protective anti-aspergillus host responses during the early stages of invasive aspergillosis are critically dependent on neutrophil recruitment, and several lines of evidence support that there is an important role for il-1 in ...201425048411
early molecular diagnosis of aspergillosis in a patient with acute myeloid leukaemia.diagnosis of invasive fungal infection remains challenging. here we report a case of early diagnosis of invasive aspergillosis in a neutropenic patient affected by acute myeloid leukaemia, achieved through the detection of aspergillus fumigatus species-specific ribonucleic acid sequences by a sensitive multiplex real-time polymerase chain reaction-based molecular assay. thanks to the early diagnosis, targeted therapy was promptly established and the severe fungal infection controlled, allowing t ...201425024994
in vitro induction of apoptosis by isosclerone from marine-derived fungus aspergillus fumigatus.in the present study, we investigated the apoptotic effects of isosclerone from marine-derived fungi on human breast cancer mcf-7 cells. treatment with isosclerone exhibited a characteristic feature of apoptosis including significant cytotoxicity and dna fragmentation in cancer cells. in addition, the apoptosis induction abilities of the isosclerone was studied by analyzing the expression of caspase-3, -8 and -9, bcl-2 family, nf-κ-b p50, p65, and ikk proteins. western blot and rt-pcr analysis h ...201425011914
fungal model systems and the elucidation of pathogenicity determinants.fungi have the capacity to cause devastating diseases of both plants and animals, causing significant harvest losses that threaten food security and human mycoses with high mortality rates. as a consequence, there is a critical need to promote development of new antifungal drugs, which requires a comprehensive molecular knowledge of fungal pathogenesis. in this review, we critically evaluate current knowledge of seven fungal organisms used as major research models for fungal pathogenesis. these ...201425011008
anti ige antibody as treatment of allergic bronchopulmonary aspergillosis in a patient with cystic fibrosis.allergic bronchopulmonary aspergillosis (abpa) occurs in 7-9% of patients with cystic fibrosis (cf) and causes a worsening of lung function and respiratory symptoms. standard treatment of abpa consists of oral steroids; however, higher corticosteroid therapy associated to antifungal agent (itraconazole) long-term treatments are often required to reduce respiratory exacerbations and to prevent progressive lung damage. here we describe the case of a girl with cf who experienced clinical and functi ...201425010610
multi-azole-resistant aspergillus fumigatus in the environment in tanzania.azole resistance in aspergillus fumigatus isolates has been increasingly reported with variable prevalence worldwide and is challenging the effective management of aspergillosis. here we report the coexistence of both tr₃₄/l98h and tr₄₆/y121f/t289a resistance mechanisms in azole-resistant a. fumigatus (araf) isolates originating from tanzania, africa.201425006238
molecular detection of candida spp. and aspergillus fumigatus in bronchoalveolar lavage fluid of patients with ventilator-associated pneumonia.ventilator-associated pneumonia (vap) is a common nosocomial infection in critically ill patients with high morbidity and mortality rates. the etiology of vap is usually bacterial. opportunistic fungi such as candida and aspergillus species (spp.) are found frequently in the respiratory track secretions of immunocompetent critically ill patients known as colonization. contribution of fungi colonization to severe bacterial vap and poor prognosis of these patients has been documented in several st ...201425002894
feasibility of mitochondrial single nucleotide polymorphisms to detect and identify aspergillus fumigatus in clinical samples.invasive aspergillosis (ia) is a concerning fungal infection among immunocompromised patients due to the poor outcomes in its treatment related with the delay in an accurate diagnosis. therefore, this study aimed to select informative mitochondrial single nucleotide polymorphism (snp) markers suitable for detection and identification of aspergillus fumigatus in clinical specimens. four mitochondrial snp markers were selected (cox_488, cytb_246, nad1_802, and nc_171) and tested on clinical and en ...201424998456
large-scale transcriptional response to hypoxia in aspergillus fumigatus observed using rnaseq identifies a novel hypoxia regulated ncrna.we utilized rnaseq analysis of the aspergillus fumigatus response to early hypoxic condition exposure. the results show that more than 89% of the a. fumigatus genome is expressed under normoxic and hypoxic conditions. replicate samples were highly reproducible; however, comparisons between normoxia and hypoxia revealed that >23 and 35% of genes were differentially expressed after 30 and 120 min of hypoxia exposure, respectively. consistent with our previous report detailing transcriptomic and pr ...201424996522
comparison of four automated nucleic acid extraction platforms for the recovery of dna from aspergillus fumigatus.invasive aspergillosis is a significant cause of morbidity and mortality within at-risk groups. directed antifungal chemotherapy, guided by effective screening algorithms that incorporate reliable and validated molecular assays, reduces the morbidity associated with empirical administration and allows earlier diagnosis. the efficient extraction of nucleic acid from aspergillus fumigatus is the main limiting factor for successful aspergillus pcr from clinical specimens. with the integration of au ...201424987100
the application of laser microdissection in molecular detection and identification of aspergillus fumigatus from murine model of acute invasive pulmonary aspergillosis.invasive aspergillosis (ia) is a major concern in patients with severe immune deficiency. as antifungal susceptibility varies in different fungal pathogens, accurate and timely identification of species is becoming imperative for guidance of therapy and reducing high mortality rates in patients with ia. but, in fact, the diagnosis is challenging and new validated techniques are required for the detection and identification of clinically relevant isolates. the laser capture microdissection (lcm) ...201424973974
synthesis, anti-microbial and molecular docking studies of quinazolin-4(3h)-one derivatives.in this work, synthesis, antimicrobial activities and molecular docking studies of some new series of substituted quinazolinone 2a-h and 3a-d were described. starting form 2-aminobenzamide derivatives 1, a new series of quinazolinone derivatives has been synthesized, in high yields, assisted by microwave and classical methods. some of these substituted quinazolinones were tested for their antimicrobial activity against gram-negative bacteria (pseudomonas aeruginosa and esherichia coli) and gram- ...201424968329
testing an innovative device against airborne aspergillus contamination.aspergillus fumigatus is a major airborne nosocomial pathogen that is responsible for severe mycosis in immunocompromised patients. we studied the efficacy of an innovative mobile air-treatment device in eliminating a. fumigatus from the air following experimental massive contamination in a high-security room. viable mycological particles were isolated from sequential air samples in order to evaluate the device's effectiveness in removing the fungus. the concentration of airborne conidia was red ...201424965945
cut-off values of serum ige (total and a. fumigatus -specific) and eosinophil count in differentiating allergic bronchopulmonary aspergillosis from asthma.the cut-off values of immunological tests employed in diagnosis of allergic bronchopulmonary aspergillosis (abpa) have never been validated. herein, we compare the immunological findings in patients with abpa and asthma using receiver operating characteristic analysis. consecutive asthmatic subjects underwent all the following investigations: aspergillus skin test, ige levels (total and a. fumigatus-specific), aspergillus precipitins, eosinophil count, chest radiograph and ct chest. there were 3 ...201424963741
fumigaclavines d-h, new ergot alkaloids from endophytic aspergillus fumigatus.ergot alkaloids are toxins which are produced biotechnologically on an industrial scale. the chemical investigation of endophytic aspergillus fumigatus resulted in the isolation of five new ergot alkaloids named fumigaclavines d-h (2-6), along with three known analogues, fumigaclavine c (1), festuclavine (7), and fumigaclavine a (8). their structures were unequivocally elucidated by extensive spectroscopic analyses in association with x-ray single-crystal diffraction. fumigaclavines d-h are inte ...201425127024
regulation of nonribosomal peptide synthesis: bis-thiomethylation attenuates gliotoxin biosynthesis in aspergillus fumigatus.gliotoxin is a redox-active nonribosomal peptide produced by aspergillus fumigatus. like many other disulfide-containing epipolythiodioxopiperazines, a bis-thiomethylated form is also produced. in the case of gliotoxin, bisdethiobis(methylthio)gliotoxin (bmgt) is formed for unknown reasons by a cryptic enzyme. here, we identify the s-adenosylmethionine-dependent gliotoxin bis-thiomethyltransferase (gtma), which converts dithiogliotoxin to bmgt. this activity, which is induced by exogenous glioto ...201425126990
miliary nodules: an unusual presentation of allergic bronchopulmonary aspergillosis.allergic bronchopulmonary aspergillosis (abpa) is an immune-mediated inflammatory disease caused by hypersensitivity to aspergillus fumigatus. a wide spectrum of plain radiographic appearances has been described in abpa, though none are pathognomonic of abpa. the common radiological abnormalities encountered are fleeting pulmonary opacities, bronchiectasis, and mucoid impaction. uncommon radiological findings encountered in abpa include pulmonary masses, perihilar opacities simulating hilar aden ...201425125822
a questionnaire-based study on the role of environmental factors in allergic bronchopulmonary aspergillosis.allergic bronchopulmonary aspergillosis (abpa) is an immunological disorder caused by hypersensitivity against aspergillus fumigatus. the pathogenesis of abpa remains unknown. few studies have investigated the role of environmental factors in pathogenesis of abpa. herein, we investigate the role of environmental factors in abpa.201425125809
aspergillus fumigatus harbouring the sole y121f mutation shows decreased susceptibility to voriconazole but maintained susceptibility to itraconazole and posaconazole.voriconazole, itraconazole and posaconazole are members of the azole family and widely used for the treatment of aspergillosis. they act by inhibiting the activity of the fungal cyp51a enzyme. the emergence of environmental azole-resistant aspergillus fumigatus strains raises major concerns for human health.201425125676
calcineurin-mediated regulation of hyphal growth, septation, and virulence in aspergillus fumigatus.calcineurin is a heterodimeric protein phosphatase complex composed of catalytic (cnaa) and regulatory (cnab) subunits and plays diverse roles in regulating fungal stress responses, morphogenesis, and pathogenesis. fungal pathogens utilize the calcineurin pathway to survive in the host environment and cause life-threatening infections. the immunosuppressive calcineurin inhibitors (fk506 and cyclosporine a) are active against fungi, making calcineurin a promising antifungal drug target. here, we ...201425118871
scaffold hopping of sampangine: discovery of potent antifungal lead compound against aspergillus fumigatus and cryptococcus neoformans.discovery of novel antifungal agents against aspergillus fumigatus and cryptococcus neoformans remains a significant challenge in current antifungal therapy. herein the antifungal natural product sampangine was used as the lead compound for novel antifungal drug discovery. a series of d-ring scaffold hopping derivatives were designed and synthesized to improve antifungal activity and water solubility. among them, the thiophene derivative s2 showed broad-spectrum antifungal activity, particularly ...201425115626
chemical composition and antimicrobial activity of the essential oil from allium hookeri consumed in xishuangbanna, southwest china.the essential oil from the rhizomes of allium hookeri thwaites, obtained by simultaneous distillation extraction, was analyzed by gc-ms. di-2-propenyl trisulfide (31.8%), diallyl disulfide (28.4%), and dipropyl trisulfide (8.4%) were the main constituents among the thirteen identified components. the essential oil showed strong activity against aspergillus fumigatus and candida albicans with mic (the minimal inhibitory concentration) and mbc (minimal bactericidal concentration) values ranging fr ...201425115101
passive surveillance for azole-resistant aspergillus fumigatus, united states, 2011-2013.emergence of aspergillus fumigatus strains containing mutations that lead to azole resistance has become a serious public health threat in many countries. nucleotide polymorphisms leading to amino acid substitutions in the lanosterol demethylase gene (cyp51a) are associated with reduced susceptibility to azole drugs. the most widely recognized mutation is a lysine to histidine substitution at aa 98 (l98h) and a duplication of the untranscribed promoter region, together known as tr34/l98h. this m ...201425148217
immunoproteome of aspergillus fumigatus using sera of patients with invasive aspergillosis.invasive aspergillosis is a life-threatening lung or systemic infection caused by the opportunistic mold aspergillus fumigatus. the disease affects mainly immunocompromised hosts, and patients with hematological malignances or who have been submitted to stem cell transplantation are at high risk. despite the current use of platelia™ aspergillus as a diagnostic test, the early diagnosis of invasive aspergillosis remains a major challenge in improving the prognosis of the disease. in this study, w ...201425141105
in vivo efficacy of a synthetic coumarin derivative in a murine model of aspergillosis.despite advances in therapeutic modalities, aspergillosis remains a leading cause of mortality. this has necessitated the identification of effective and safe antifungal molecules. in the present study, in vivo safety and antifungal efficacy of a coumarin derivative, n, n, n-triethyl-11-(4-methyl-2-oxo-2h-benzopyran-7-yloxy)-11-oxoundecan-1-aminium bromide (scd-1), was investigated. the maximum tolerable dose of compound was determined according to oecd 423 guidelines. the compound could be assi ...201425140804
eucast testing of isavuconazole susceptibility in aspergillus: comparison of results for inoculum standardization using conidium counting versus optical density.the eucast e.def9.1 standard recommends standardization of the inoculum concentration by conidium counting using a hemocytometer rather than a spectrophotometer. in this study, we investigated whether the choice of these methods influenced isavuconazole mics. a blinded collection of 30 molecularly characterized azole-resistant isolates and 10 wild-type aspergillus fumigatus isolates was shared with four different laboratories. additionally, each laboratory selected approximately 100 a. fumigatus ...201425136005
the biology of pulmonary aspergillus infections.pulmonary aspergillus infections are mainly caused by aspergillus fumigatus and can be classified based on clinical syndromes into saphrophytic infections, allergic disease and invasive disease. invasive pulmonary aspergillosis, occurring in immunocompromised patients, reflects the most serious disease with a high case-fatality rate. patients with cystic fibrosis and severe asthma might develop allergic bronchopulmonary aspergillosis, while saphrophytic infections are observed in patients with l ...201425135079
mangostanaxanthones i and ii, new xanthones from the pericarp of garcinia mangostana.two new xanthones: mangostanaxanthones i (3) and ii (5) were isolated from the pericarp of garcinia mangostana, along with four known xanthones: 9-hydroxycalabaxanthone (1), parvifolixanthone c (2), α-mangostin (4), and rubraxanthone (6). their structures were elucidated on the basis of ir, uv, 1d, 2d nmr, and ms spectroscopic data, in addition to comparison with literature data. the isolated compounds were evaluated for their antioxidant, antimicrobial, and quorum-sensing inhibitory activities. ...201425128900
synthesis and antimicrobial activity of novel 5-aminoimidazole-4-carboxamidrazones.a mild and simple method was developed to prepare a series of fifteen 5-aminoimidazole 4-carboxamidrazones, starting from the easily accessible 5-amino-4-cyanoformimidoyl imidazoles. the antimicrobial activity of these novel amidrazones was screened against gram positive (staphylococcus aureus) and gram negative (escherichia coli, pseudomonas aeruginosa) bacteria and candida sp. (candida albicans, candida krusei, candida parapsilosis). only a subset of compounds displayed fair-moderate activity ...201425193230
acapsular cryptococcus neoformans activates the nlrp3 inflammasome.cryptococcus neoformans (c. neoformans) is an opportunistic fungal pathogen that mainly infects immunocompromised individuals such as aids patients. although cell surface receptors for recognition of c. neoformans have been studies intensively, cytoplasmic recognition of this pathogen remains unclear. as an important detector of pathogen infection, inflammasome can sense and get activated by infection of various pathogens, including pathogenic fungi such as candida albicans and aspergillus fumig ...201425193031
erythropoietin combined with liposomal amphotericin b improves outcome during disseminated aspergillosis in mice.disseminated aspergillosis is responsible for a high mortality rate, despite the use of antifungal drugs. adjuvant therapies are urgently needed to improve the outcome. the aim of this study was to demonstrate that the cytoprotective effect of erythropoietin (epo) combined with amphotericin b can reduce the mortality rate in a murine model of disseminated aspergillosis. after infection with aspergillus fumigatus, neutropenic mice were randomized to receive vehicle or 7.5 mg/kg liposomal amphoter ...201425352847
comparative pharmacodynamics of posaconazole in neutropenic murine models of invasive pulmonary aspergillosis and mucormycosis.we used two established neutropenic murine models of pulmonary aspergillosis and mucormycosis to explore the association between the posaconazole area under the concentration-time curve (auc)-to-mic ratio (auc/mic) and treatment outcome. posaconazole serum pharmacokinetics were verified in infected mice to ensure that the studied doses reflected human exposures with the oral suspension, delayed-release tablet, and intravenous formulations of posaconazole. sinopulmonary infections were then induc ...201425182639
ige sensitization to aspergillus fumigatus is not a bystander phenomenon in cystic fibrosis lung disease. 201425180753
identification of immunogenic antigens from aspergillus fumigatus by direct multiparameter characterization of specific conventional and regulatory cd4+ t cells.cd4(+) t cells orchestrate immune responses against fungi, such as aspergillus fumigatus, a major fungal pathogen in humans. the complexity of the fungal genome and lifestyle questions the existence of one or a few immune-dominant ags and complicates systematic screening for immunogenic ags useful for immunotherapy or diagnostics. in this study, we used a recently developed flow cytometric assay for the direct ex vivo characterization of a. fumigatus-specific cd4(+) t cells for rapid identificat ...201425172488
in vitro protease inhibition and cytotoxicity of aspergillus fumigatus biomolecules secreted under long-term aerated conditions.the fatality rate of invasive aspergillosis (ia) is still very high, especially in prolonged and untreated pulmonary cases. aspergillus fumigatus is the main causative agent of ia and investigation of its metabolites could provide valuable insight into virulence factor(s) associated with this organism. we evaluated the a. fumigatus culture filtrate (cf) products generated during short- and long-term aerated and non-aerated conditions and tested for (i) inhibition of cysteine or serine proteases ...201425170296
antibiotic management of lung infections in cystic fibrosis. ii. nontuberculous mycobacteria, anaerobic bacteria, and fungi.airway infections are a key component of cystic fibrosis (cf) lung disease. whereas the approach to common pathogens such as pseudomonas aeruginosa is guided by a significant body of evidence, other infections often pose a considerable challenge to treating physicians. in part i of this series on the antibiotic management of difficult lung infections, we discussed bacterial organisms including methicillin-resistant staphylococcus aureus, gram-negative bacterial infections, and treatment of multi ...201425167882
dectin-1 is expressed in human lung and mediates the proinflammatory immune response to nontypeable haemophilus influenzae.the c-type lectin receptor dectin-1 is expressed mainly on myeloid cells mediating the immune response targeting respiratory pathogens such as aspergillus fumigatus and mycobacterium tuberculosis. the pulmonary epithelium serves as an important interface for interactions between these pathogens and the respiratory tract. therefore, we analyzed the expression pattern of dectin-1 in the human lung. immunohistochemically stained human lung sections from 17 out of 19 individuals were positive for de ...201425161190
axl receptor blockade protects from invasive pulmonary aspergillosis in mice.aspergillus fumigatus is a sporulating fungus found ubiquitously in the environment, which is quickly contained in the immunocompetent host but can cause lethal invasive aspergillosis in the immunocompromised host. we have recently demonstrated that axl (one member of the tyro3, axl, mertk receptor family) is a key regulator of antiviral immune responses in the lung. in this study, we investigated the role of axl in antifungal immunity in a model of invasive pulmonary aspergillosis (ipa). in thi ...201425156363
improved thermostability of esterase from aspergillus fumigatus by site-directed mutagenesis.a 1.020-bp esterase gene, estq, encoding for a protein of 339 amino acids, was cloned from aspergillus fumigatus and expressed in e. coli. estq exhibited the optimal activity around 40 °c and ph 9.0. in order to obtain more thermostable esterases, three mutants (a134t, v160t, a134t-v160t) were constructed by site-directed mutagenesis and also characterized for further research. compared to a134t and v160t displaying their optimum activity at 40 °c, a134t-v160t exhibited a 5 °c higher optimal tem ...201425152411
fungal culture and sensitisation in asthma, cystic fibrosis and chronic obstructive pulmonary disorder: what does it tell us?collectively asthma, chronic obstructive pulmonary disorder (copd) and cystic fibrosis (cf) are very common, important causes of disease and ill health. filamentous fungal colonisation of the airways can occur in all three disease groups, although the clinical relevance is unclear. allergic bronchopulmonary aspergillosis (abpa) is a well-recognised severe complication of airway colonisation associated primarily with aspergillus fumigatus. fungal colonisation may have a deleterious effect without ...201425151366
carum copticum and thymus vulgaris oils inhibit virulence in trichophyton rubrum and aspergillus spp.emergence of drug-resistant strains has demanded for alternative means of combating fungal infections. oils of carum copticum and thymus vulgaris have long been used in ethnomedicine for ailments of various fungal infections. since their activity has not been reported in particular against drug-resistant fungi, this study was aimed to evaluate the effects of oils of c. copticum and t. vulgaris on the growth and virulence of drug-resistant strains of aspergillus spp. and trichophyton rubrum. the ...201425242937
role of trem-1 in response to aspergillus fumigatus infection in corneal epithelial cells.triggering receptor expressed on myeloid cells-1 (trem-1) is a cell surface receptor that is highly expressed in inflammatory lesions caused by infectious agents such as bacteria and fungi and amplifies immune responses. the aim of the current study was to investigate trem-1 expression in corneal epithelial cells infected by aspergillus fumigatus (a. fumigatus) and evaluate its role. in this study, infection with a. fumigatus upregulated trem-1 expression in corneal epithelial cells both in vitr ...201425242387
whole-genome comparison of aspergillus fumigatus strains serially isolated from patients with aspergillosis.the emergence of azole-resistant strains of aspergillus fumigatus during treatment for aspergillosis occurs by a mutation selection process. understanding how antifungal resistance mechanisms evolve in the host environment during infection is of great clinical importance and biological interest. here, we used next-generation sequencing (ngs) to identify mutations that arose during infection by a. fumigatus strains sequentially isolated from two patients, one with invasive pulmonary aspergillosis ...201425232160
vitamin d and experimental invasive aspergillosis.immune cells express the vitamin d receptor and vitamin d metabolizing enzymes. favorable vitamin d effects have been indicated in tuberculosis. vitamin d deficiency increases t helper (th) 2 responses to aspergillus, and it suppresses th2 responses in cystic fibrosis-allergic bronchopulmonary aspergillosis. can vitamin d modulate the proinflammatory effects of amphotericin b (amb) therapy in aspergillosis? groups of mice were infected intravenously (iv) with 3-8 × 10(6) aspergillus fumigatus co ...201425231772
[the clinical monitoring of invasive aspergillosis in surgical intensive care unit during 10 years].to investigate the invasive aspergillosis (ia) status in a surgical intensive care unit (sicu).201425230864
chemical composition, antioxidant, antimicrobial and anti-inflammatory activities of the stem and leaf essential oils from piper flaviflorum from xishuangbanna, sw china.the present study is the first investigation of the chemical composition, antioxidant, antimicrobial and anti-inflammatory activities of the stem and leaf essential oils from piper flaviflorum c.dc (seop and leop), a plant that has been consumed as a wild vegetable, and used as medicine, and spice by the ethnic groups in xishuangbanna, sw china. analyzed by gc-ms, 42 and 30 components were identified representing 90.1% and 95.3% of the seop and leop, with (e)-nerolidol (16.7% and 40.5%), beta-ca ...201425230516
insights in the kinetic mechanism of the eukaryotic baeyer-villiger monooxygenase bvmoaf1 from aspergillus fumigatus af293.this work reports a detailed kinetic study of the recently discovered bvmoaf1 from aspergillus fumigatus af293. by performing steady state and pre-steady state kinetic analyses, it was demonstrated that the rate of catalysis is partially limited by the nadph-mediated reduction of the flavin cofactor, a unique hallmark of bvmoaf1. in addition, the oxygenating c4a-(hydro)peroxyflavin intermediate could be spectrophotometrically detected and it was found to be the most stable among all analyzed bvm ...201425230086
submicronic fungal bioaerosols: high-resolution microscopic characterization and quantification.submicronic particles released from fungal cultures have been suggested to be additional sources of personal exposure in mold-contaminated buildings. in vitro generation of these particles has been studied with particle counters, eventually supplemented by autofluorescence, that recognize fragments by size and discriminate biotic from abiotic particles. however, the fungal origin of submicronic particles remains unclear. in this study, submicronic fungal particles derived from aspergillus fumiga ...201425217010
bioconversion of tea polyphenols to bioactive theabrownins by aspergillus fumigatus.theabrownins (tb) are water-soluble phenolic compounds associated with the various health benefits of pu-erh tea, a post-fermented chinese dark tea. this work reports on the production of theabrownins from infusions of sun-dried green tea leaves using a pure culture of aspergillus fumigatus isolated from a solid-state pu-erh tea fermentation. a theabrownins yield of 158 g kg(-1) sun-dried green tea leaves was obtained in 6 days at 45 °c in an aerobic fermentation. in a 2 l fermenter, the yield o ...201425214210
human dendritic cell subsets display distinct interactions with the pathogenic mould aspergillus fumigatus.the mould aspergillus fumigatus is primarily an opportunistic pathogen of immunocompromised patients. once fungal spores have been inhaled they encounter cells of the innate immune system, which include dendritic cells (dcs). dcs are the key antigen-presenting cells of the immune system and distinct subtypes, which differ in terms of origin, morphology and function. this study has systematically compared the interactions between a. fumigatus and myeloid dcs (mdcs), plasmacytoid dcs (pdcs) and mo ...201425200858
assessment of aspergillus fumigatus burden in lungs of intratracheally-challenged turkeys (meleagris gallopavo) by quantitative pcr, galactomannan enzyme immunoassay, and quantitative culture.aspergillus fumigatus remains a major respiratory pathogen in birds and treatment is still difficult. we challenged different groups of few-day-old turkeys via intratracheal aerosolisation with increasing concentrations (10(5) up to 10(8)) of conidia using a microsprayer(®) device. the fungal burden was assessed by real-time pcr, galactomannan dosage, cfu counting and histopathological evaluation in order to provide a comparison of these results within each inoculum groups. significant mortality ...201425199572
a proteomic approach to investigating gene cluster expression and secondary metabolite functionality in aspergillus fumigatus.a combined proteomics and metabolomics approach was utilised to advance the identification and characterisation of secondary metabolites in aspergillus fumigatus. here, implementation of a shotgun proteomic strategy led to the identification of non-redundant mycelial proteins (n = 414) from a. fumigatus including proteins typically under-represented in 2-d proteome maps: proteins with multiple transmembrane regions, hydrophobic proteins and proteins with extremes of molecular mass and pi. indire ...201425198175
chip-seq reveals a role for crza in the aspergillus fumigatus high-osmolarity glycerol response (hog) signalling pathway.aspergillus fumigatus is an opportunistic pathogen and allergen of mammals. calcium signalling is essential for a. fumigatus pathogenicity and is regulated by the crza transcription factor. we used chip-seq (chromatin immunoprecipitation dna sequencing) to explore crza gene targets in a. fumigatus. in total, 165 potential binding peaks including 102 directly regulated genes were identified, resulting in the prediction of the a[gt][cg]ca[ac][ag] crza-binding motif. the 102 crza putatively regulat ...201425196896
erratum: cloning, overexpression and biocatalytic exploration of a novel baeyer-villiger monooxygenase from aspergillus fumigatus af293. 201426267109
assessment techniques to detect aspergillus fumigatus in different samples of immunosuppressed male western albino rats.there are several conventional, immunological and molecular techniques to diagnose the fungi that cause aspergillosis in biological samples; these methods have some advantages and disadvantages.201425774269
effect of phosphatidylcholine on the level expression of plc genes of aspergillus fumigatus by real time pcr method and investigation of these genes using bioinformatics analysis.phosphlipases are a group of enzymes that breakdown phosphatidylcholine (phospholipids) molecules producing second products. these produced products have a divers role in the cell like signal transduction and digestion in humans. in this research the effect of phosphatidylcholine on the expression of plc genes of a. fumigatus was studied. the plc genes of this fungus were also interrogated using bioinformatics studies.201425705361
comparison of diagnostic tools for the detection of aspergillosis in blood samples of experimentally infected falcons.antemortem diagnosis of avian aspergillosis is very challenging. diagnostic assays using blood samples would aid in an early and more definitive diagnosis. in the current study, detection of anti-aspergillus antibodies, aspergillus antigen, and aspergillus toxin (fumigaclavine a), protein electrophoresis and measurement of acute-phase protein concentrations were performed on serum of 18 adult and plasma of 21 juvenile gyr-saker hybrid falcons (falco rusticolus x falco cherrug). adult (n = 15) an ...201425619004
a novel fungus concentration-dependent rat model for acute invasive fungal rhinosinusitis: an experimental study.acute invasive fungal rhinosinusitis is a lethal infectious process afflicting immunocompromised individuals. knowledge about this disease is still limited due to the scarcity of animal models designed to study the pathogenesis of this infection. mast cells are tissue-resident immune cells that participate in a variety of allergic and inflammatory conditions. limited attention has been given to the role of mast cells in acute invasive fungal rhinosinusitis. therefore, the objectives of this stud ...201425526739
gas6'ing the innate immune response during experimental asthma.growth arrest-specific gene 6 (gas6) binds tyro3, axl, and mertk (tam) receptors and exerts prominent effects in many diseases, but little is known about its role in asthma. herein, we examined the role of gas6 and tam receptors differentially in an experimental asthma model driven by aspergillus fumigatus. a. fumigatus-sensitized mice were challenged with live a. fumigatus conidia, and airway hyperresponsiveness and airway remodeling were determined 28 days later. when administered to mice from ...201425525737
[a case of lung abscess due to aspergillus viridinutans in a patient with aplastic anemia].a 75-year-old woman with aplastic anemia was admitted to our university hospital because of a dry cough that had persisted for a month. chest computed tomography showed a mass shadow with a central low attenuation area in the lower lobe of the left lung. filamentous fungus resembling aspergillus fumigatus was cultured from the specimens obtained by transthoracic needle aspiration biopsy and bronchoalveolar lavage. the initial diagnosis was a lung abscess due to a. fumigatus, although the patient ...201425764808
conserved and varied dinucleotide sequences in the genomes of three aspergillus species.both guanine-cytosine content and nucleosome occupancy are higher in exons than in introns. in this study, the association between the frequencies of the dinucleotide sequences and the nucleosome occupancy of the exons and introns of the genes of aspergillus fumigatus, aspergillus nidulans, and aspergillus oryzae was studied. the frequency of the dinucleotide sequences aa (tt), at, and ta in the introns was more than that in the exons. in addition, the frequency of these sequences in the regions ...201425564023
malassezia yeasts activate the nlrp3 inflammasome in antigen-presenting cells via syk-kinase signalling.although being a normal part of the skin flora, yeasts of the genus malassezia are associated with several common dermatologic conditions including pityriasis versicolour, seborrhoeic dermatitis (sd), folliculitis, atopic eczema/dermatitis (ae/ad) and dandruff. while malassezia spp. are aetiological agents of pityriasis versicolour, a causal role of malassezia spp. in ae/ad and sd remains to be established. previous reports have shown that fungi such as candida albicans and aspergillus fumigatus ...201425267545
aspergillus pseudoaneurysm post aortic valve replacement.thoracic aortic mycotic aneurysms caused by aspergillus fumigatus postoperatively are rare and devastating complications. these cases are usually attributed to intraoperative contamination of surgical equipment. we present a patient who had an ascending aortic mycotic aneurysm 20 weeks post aortic valve replacement. a high index of suspicion allowed for diagnosis and prompt treatment, although the patient presented in an unusual manner. treatment included both medical and surgical therapy to min ...201426798740
[management of ocular and orbital complications in acute sinusitis].describe the clinical presentations of orbital complications of acute sinusitis and discuss therapeutic approaches.201425264151
novel and sensitive qpcr assays for the detection and identification of aspergillosis causing species.despite concerted efforts, diagnosis of aspergillosis is still a great challenge to clinical microbiology laboratories. along with the requirement for high sensitivity and specificity, species-specific identification is important. we developed rapid, sensitive and species-specific qpcr assays using the taqman technology for the detection and identification of aspergillus fumigatus and aspergillus terreus. the assays were designed to target orthologs of the streptomyces factor c gene that are onl ...201425261942
pulmonary immune responses to aspergillus fumigatus in rats.to evaluate immunologic mechanisms underlying aspergillus fumigatus pulmonary infections in immunocompetent dark agouti (da) and albino oxford (ao) rats recognized as being susceptible to some inflammatory diseases in different manners.201425256858
myeloid derived hypoxia inducible factor 1-alpha is required for protection against pulmonary aspergillus fumigatus infection.hypoxia inducible factor 1α (hif1α) is the mammalian transcriptional factor that controls metabolism, survival, and innate immunity in response to inflammation and low oxygen. previous work established that generation of hypoxic microenvironments occurs within the lung during infection with the human fungal pathogen aspergillus fumigatus. here we demonstrate that a. fumigatus stabilizes hif1α protein early after pulmonary challenge that is inhibited by treatment of mice with the steroid triamcin ...201425255025
multiple intracranial fungal abscesses in an immunocompetent infant treated surgically.intracerebral abscess are rare in neonates and infants. we present a rare case of 4-month-old immunocompetent infant with multiple intracranial fungal abscess. right frontoparietal craniotomy was done with excision of multicystic mass containing 200cc of dirty colored fluid. biopsy and culture of abscess came as aspergillus fumigates. patient received parental amphotericin b. an immunocompetent infant with intracranial aspergillosis is rare. we advocate combination of surgical excision with pare ...201425250076
antimicrobial activity, toxicity and selectivity index of two biflavonoids and a flavone isolated from podocarpus henkelii (podocarpaceae) leaves.different parts of podocarpus henkelii have been used in many cultures around the world to treat ailments such as cholera, stomach diseases, rheumatism, cancer, canine distemper in dogs and gall sickness in cattle. the aim of this study was to evaluate the biological activity and toxicity of isolated compounds from podocarpus henkelii after an earlier study indicated a promising activity in crude extracts against viral pathogens of veterinary importance.201425293523
whole glucan particles as a vaccine against murine aspergillosis.vaccination with heat-killed saccharomyces cerevisiae (hky) protects against experimental infection by pathogenic fungi of five genera. here we tested whether purified saccharomyces cell wall β-glucan could induce protection against systemic aspergillosis. cd-1 mice were given three weekly vaccine doses subcutaneously prior to intravenous infection with aspergillus fumigatus. mice received pbs, 2.5 mg hky, whole glucan particles (wgp), wgp conjugated to bsa (0.06 to 12 mg per dose), a soluble me ...201425288643
structure of an aspergillus fumigatus old yellow enzyme (easa) involved in ergot alkaloid biosynthesis.the aspergillus fumigatus old yellow enzyme (oye) easa reduces chanoclavine-i aldehyde to dihydrochanoclavine aldehyde and works in conjunction with festuclavine synthase at the branchpoint for ergot alkaloid pathways. the crystal structure of the fmn-loaded easa was determined to 1.8 å resolution. the active-site amino acids of oye are conserved, supporting a similar mechanism for reduction of the α/β-unsaturated aldehyde. the c-terminal tail of one monomer packs into the active site of a monom ...201425286934
luliconazole for the treatment of fungal infections: an evidence-based review.luliconazole is an imidazole antifungal agent with a unique structure, as the imidazole moiety is incorporated into the ketene dithioacetate structure. luliconazole is the r-enantiomer, and has more potent antifungal activity than lanoconazole, which is a racemic mixture. in this review, we summarize the in vitro data, animal studies, and clinical trial data relating to the use of topical luliconazole. preclinical studies have demonstrated excellent activity against dermatophytes. further, in vi ...201425285056
mycological monitoring of selected aquatic ecosystems in the context of epidemiological hazards. drinking water.many species of microfungi are reported in aquatic ecosystems with different frequency. their number constantly fluctuates depending on the concentration of environmental and anthropogenic factors. drinking water, tap and bottled, is essential for the proper functioning of the human body. it is also the main component of food and hence it should be safe for human health and free of contaminants. the mycological purity of tap water in two large cities in the region (olsztyn and ostrołęka) and a s ...201425281816
identification of high-affinity copper transporters in aspergillus fumigatus.we investigated the copper metabolism of aspergillus fumigatus, which has not been characterized well. we cloned the putative copper transporters ctra2 and ctrc from a. fumigatus and investigated the functions of these transporters in copper metabolism. four putative copper transporters were identified in the a. fumigatus genome; ctra2 and ctrc complemented ctr1 functionally and localized to the plasma membrane in saccharomyces cerevisiae. ctra2 and ctrc single-deletion mutants and a double-dele ...201425281782
cerebral aspergillosis in a patient with leprosy and diabetes: a case report.opportunistic fungi are dispersed as airborne, ground and decaying matter. the second most frequent extra-pulmonary disease by aspergillus is in the central nervous system.201425280605
wedge resection for localized infectious lesions: high margin/lesion ratio guaranteed operational safety.this study aims to elucidate the risk factors of pulmonary complications for localized infectious lesions with limited resection.201425276357
resistance to antifungals that target cyp51.fungal diseases are an increasing global burden. fungi are now recognised to kill more people annually than malaria, whilst in agriculture, fungi threaten crop yields and food security. azole resistance, mediated by several mechanisms including point mutations in the target enzyme (cyp51), is increasing through selection pressure as a result of widespread use of triazole fungicides in agriculture and triazole antifungal drugs in the clinic. mutations similar to those seen in clinical isolates as ...201425320648
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