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[aspergillosis. clinical forms and treatment].invasive aspergillosis, chronic pulmonary aspergillosis and allergic bronchopulmonary aspergillosis are the clinical forms of aspergillosis. although there is a great number of aspergillus species, aspergillus fumigatus-complex is the more frequent aetiological agent, regardless of clinical form or baseline condition. the increase in immunosuppressive agents and the higher use of corticosteroids in chronic obstructive pulmonary disease have led to aspergillosis becoming more prominent in recent ...201222341751
characterization of a thermostable β-glucosidase from aspergillus fumigatus z5, and its functional expression in pichia pastoris x33.recently, the increased demand of energy has strongly stimulated the research on the conversion of lignocellulosic biomass into reducing sugars for the subsequent production, and β-glucosidases have been the focus because of their important roles in a variety fundamental biological processes and the synthesis of useful β-glucosides. although the β-glucosidases of different sources have been investigated, the amount of β-glucosidases are insufficient for effective conversion of cellulose. the goa ...201222340848
dexamethasone increases susceptibility of aspergillus fumigatus to hydrogen peroxide via down-regulation of afyap1 gene expression in vitro.glucocorticoid is speculated to be able to have aspergillus fumigatus (a. fumigatus) being more susceptible to reactive oxygen species (ros) by inhibiting afyap1, the transcription factor activating protein-1 (ap-1) homologue in a. fumigatus, which may provide a clue to expand the clinical use of glucocorticoid in patients with fungal infections. in this study, we used dexamethasone to determine the direct effect on oxidative killing susceptibility of a. fumigatus in vitro, as well as the expres ...201122340240
structural insight into the unique substrate binding mechanism and flavin redox state of udp-galactopyranose mutase from aspergillus fumigatus.udp-galactopyranose mutase (ugm) is a flavin-containing enzyme that catalyzes the reversible conversion of udp-galactopyranose (udp-galp) to udp-galactofuranose (udp-galf). as in prokaryotic ugms, the flavin needs to be reduced for the enzyme to be active. here we present the first eukaryotic ugm structures from aspergillus fumigatus (afugm). the structures are of ugm alone, with the substrate udp-galp and with the inhibitor udp. additionally, we report the structures of afugm bound to substrate ...201222334662
[prevalence of allergic bronchopulmonary aspergillosis in chinese patients with bronchial asthma].to evaluate the frequency of sensitization to aspergillus antigens and the prevalence of allergic bronchopulmonary aspergillosis (abpa) in asthmatic patients.201122333503
epidemiological cutoff values for azoles and aspergillus fumigatus based on a novel mathematical approach incorporating cyp51a sequence analysis.epidemiological cutoff values (ecv) are commonly used to separate wild-type isolates from isolates with reduced susceptibility to antifungal drugs, thus setting the foundation for establishing clinical breakpoints for aspergillus fumigatus. however, ecvs are usually determined by eye, a method which lacks objectivity, sensitivity, and statistical robustness and may be difficult, in particular, for extended and complex mic distributions. we therefore describe and evaluate a statistical method of ...201222330922
keratomycosis caused by aspergillus viridinutans: an aspergillus fumigatus-resembling mold presenting distinct clinical and antifungal susceptibility patterns.we report here a case of fungal keratitis caused by aspergillus viridinutans, a member of the genus which was found to have clinical and antifungal susceptibility characteristics distinct from the species it most closely resembles, aspergillus fumigatus. a 26-year-old woman presented with contact lens-associated keratitis, the etiologic agent of which was initially slow growing and found to be resistant to amphotericin b and voriconazole. therapeutic keratoplasty was performed and an isolate fro ...201222329455
a nebulized intra-tracheal rat model of invasive pulmonary aspergillosis.animal models are particularly useful for the study of many infectious diseases, including those caused by fungi. invasive pulmonary aspergillosis is most frequently studied in mouse models. we present here an animal model of this disease based on undernourished immunocompromised rats infected with aspergillus fumigatus spores by intra-tracheal nebulisation.201222328399
embryonated chicken eggs as alternative infection model for pathogenic fungi.embryonated eggs have been used as infection models for decades in virology and bacteriology. however, they can also be used as an attractive alternative infection model for studying fungal pathogenesis. here, we discuss some general aspects which need to be considered when working with embryonated eggs as infection models. furthermore, we provide detailed protocols and technical tips for infection of embryonated eggs with aspergillus fumigatus and candida albicans via the chorioallantois membra ...201222328397
simple assays for measuring innate interactions with fungi.in recent decades, there has been a steady rise in immunocompromised populations and consequently a dramatic increase in the clinical relevance of normally non-pathogenic and commensal fungi such as aspergillus fumigatus and candida albicans. understanding how these fungi interact with the host immune system is important for the development of immunotherapeutic approaches. here, we describe a number of methods which have been developed to investigate the interactions of fungi with host leukocyte ...201222328383
targeted gene deletion in aspergillus fumigatus using the hygromycin-resistance split-marker approach.the construction of a fungal strain that lacks a specific gene product is often accomplished by replacing the gene of interest with a selection marker using site-specific recombination. transformation of aspergillus fumigatus, like many related fungal species, must overcome two major obstacles. first, the cell wall limits the entry of exogenous dna, and second, a high rate of nonhomologous recombination leads to random ectopic integration of the marker. here, we describe an experimental strategy ...201222328371
gene disruption in aspergillus fumigatus using a pcr-based strategy and in vivo recombination in yeast.aspergillus fumigatus is a ubiquitous, filamentous fungal saprophyte and is the causative agent of the vast majority of aspergillosis in that invasive aspergillosis is the life-threatening form of infection by this fungus. the study of gene function using null mutants in this organism can be achieved through dna-mediated transformation with an engineered deletion cassette containing about 2 kb of the 5'- and 3'-flanking region of the target gene and a selectable marker. here, we describe the use ...201222328370
production of thermophilic endo-β-1,4-xylanases by aspergillus fumigatus fbspe-05 using agro-industrial by-products.in the present paper, endo-β-1,4-xylanase production by aspergillus fumigatus was evaluated in solid-state fermentation using low-cost substrates such as sugarcane bagasse (scb), brewer's spent grain (bsg), and wheat bran (wb). the partial characterization of the crude enzyme was also performed. in the experimental conditions, the highest levels of endo-β-1,4-xylanase production by a. fumigatus fbspe-05 occurred within 8 days incubation when using scb/liquid medium at 1:2 ratio (219.5 u g(-1)) a ...201222328248
inhibitory effects of gossypol, gossypolone, and apogossypolone on a collection of economically important filamentous fungi.racemic gossypol and its related derivatives gossypolone and apogossypolone demonstrated significant growth inhibition against a diverse collection of filamentous fungi that included aspergillus flavus, aspergillus parasiticus, aspergillus alliaceus, aspergillus fumigatus, fusarium graminearum, fusarium moniliforme, penicillium chrysogenum, penicillium corylophilum, and stachybotrys atra. the compounds were tested in a czapek agar medium at a concentration of 100 μg/ml. racemic gossypol and apog ...201222324794
[clinical analysis of 8 cases with acute invasive pulmonary aspergillosis in younger children].to analyze the clinical features of acute invasive pulmonary aspergillosis in younger children, in order to improve the levels of early recognition, diagnosis and management of this disease.201122321188
incidence and presentation of fungal sinusitis in patient diagnosed with chronic rhinosinusitis.significant number of patients diagnosed with chronic rhino sinusitis often tend to have a final diagnosis of fungal sinusitis. we wanted to find out (a) the incidence of patients with fungal sinusitis in those patients who were initially diagnosed as chronic rhinosinusitis. (b) the presentation of fungal sinusitis patients who were initially diagnosed as crs. retrospective chart review of 242 patients diagnosed as crs from may 2006 to april 2009. the various symptoms and signs of those diagnose ...201122319697
persistence versus escape: aspergillus terreus and aspergillus fumigatus employ different strategies during interactions with macrophages.invasive bronchopulmonary aspergillosis (ibpa) is a life-threatening disease in immunocompromised patients. although aspergillus terreus is frequently found in the environment, a. fumigatus is by far the main cause of ibpa. however, once a. terreus establishes infection in the host, disease is as fatal as a. fumigatus infections. thus, we hypothesized that the initial steps of disease establishment might be fundamentally different between these two species. since alveolar macrophages represent o ...201222319619
trypacidin, a spore-borne toxin from aspergillus fumigatus, is cytotoxic to lung cells.inhalation of aspergillus fumigatus conidia can cause severe aspergillosis in immunosuppressed people. a. fumigatus produces a large number of secondary metabolites, some of which are airborne by conidia and whose toxicity to the respiratory tract has not been investigated. we found that spores of a. fumigatus contain five main compounds, tryptoquivaline f, fumiquinazoline c, questin, monomethylsulochrin and trypacidin. fractionation of culture extracts using rp-hplc and lc-ms showed that sample ...201222319557
species-specific recognition of aspergillus fumigatus by toll-like receptor 1 and toll-like receptor 6.aspergillus fumigatus causes invasive aspergillosis, a potentially fatal infection in oncohematological patients. innate immune detection of a. fumigatus involves toll-like receptor (tlr) 4 and tlr2, which forms a heterodimer with either tlr1 or tlr6. the role of those coreceptors in aspergillus sensing is unknown.201222315281
the t788g mutation in the cyp51c gene confers voriconazole resistance in aspergillus flavus causing aspergillosis.with voriconazole (vrc) being approved as the first choice in treating invasive aspergillosis (ia) and its increasing use in treatment, a vrc-resistant strain of aspergillus flavus, the second leading cause of ia after aspergillus fumigatus, has emerged. the vrc-resistant strain of a. flavus was isolated for the first time from the surgical lung specimen of an ia patient with no response to vrc therapy. in order to ascertain the mechanism of vrc resistance, the azole target enzyme genes in this ...201222314539
expression turnover profiling to monitor the antifungal activities of amphotericin b, voriconazole, and micafungin against aspergillus fumigatus.eight highly expressed candidate genes were selected for mrna profiling to monitor the transcriptome kinetics of aspergillus fumigatus strains exposed to antifungal drugs as potential biomarkers of live cells to assess treatment efficacy. mycelia were treated with fungicidal drugs amphotericin b and voriconazole, as well as the fungistatic drug micafungin. transcription was monitored at 0, 4, 8, and 24 h posttreatment. the expression turnover profile provides a possible tool to assess antifungal ...201222314535
new antifungal cholestane and aldehyde derivatives from the red alga laurencia papillosa.the chloroform/methanol extract of the red alga, laurencia papillosa, collected from the red sea in saudi arabia, was found to contain two cholestane derivatives: 3alpha, 6alpha-dihydroxy-5beta-cholestan-12-one (1) and the known, 6beta-hydroxycholest-4-en-3-one (2), which was isolated separately in a pure form for the first time. in addition to these compounds, a new aldehyde derivative, (e)-2-{(e) tridec-2-en-2-yl} heptadec-2-enal (3), was isolated. the structures of all compounds were establis ...201122312715
assessment of aspergillus fumigatus in guinea pig bronchoalveolar lavages and pulmonary tissue by culture and realtime polymerase chain reaction studies.in this study we pursued a diagnostic target in aspergillus fumigatus (af) by using qualitative realtime pcr combined with proprietary dna primers and a hydrolysis probe specific for this fungal target. qualitative realtime pcr is a diagnostic tool that utilizes realtime pcr technology and detects the presence or absence target specific dna within a predetermined detection range. respiratory tissue and fluids from experimentally infected guinea pigs were tested by extracting dna from the samples ...201222312282
a comparative study of hydrolysis and transglycosylation activities of fungal β-glucosidases.β-glucosidases (bgs) from aspergillus fumigatus, aspergillus niger, aspergillus oryzae, magnaporthe grisea, neurospora crassa, and penicillium brasilianum were purified to homogeneity, and investigated for their (simultaneous) hydrolytic and transglycosylation activity in samples with high concentrations of either cellobiose or glucose. the rate of the hydrolytic process (which converts one cellobiose to two glucose molecules) shows a maximum around 10-15 mm cellobiose and decreases with further ...201322311644
transcriptomic and proteomic analyses of the aspergillus fumigatus hypoxia response using an oxygen-controlled fermenter.aspergillus fumigatus is a mold responsible for the majority of cases of aspergillosis in humans. to survive in the human body, a. fumigatus must adapt to microenvironments that are often characterized by low nutrient and oxygen availability. recent research suggests that the ability of a. fumigatus and other pathogenic fungi to adapt to hypoxia contributes to their virulence. however, molecular mechanisms of a. fumigatus hypoxia adaptation are poorly understood. thus, to better understand how a ...201222309491
current understanding of ptx3 protective activity on aspergillus fumigatus infection.infection caused by aspergillus fumigatus remains a major therapeutic challenge in immunocompromised individuals. innate immunity represents the first line of defense against pathogens. in the last 20 years, several proteins belonging to this arm of the immune system have been characterized as being endowed with antifungal activity. among these, the prototype long pentraxin ptx3 has been identified as a non-redundant protective factor against infections caused by a. fumigatus. a number of releva ...201222309253
a novel dehydrin-like protein from aspergillus fumigatus regulates freezing tolerance.we recently reported on dpra and dprb, dehydrin-like proteins involved in the protection against oxidative, osmotic and ph stress in aspergillus fumigatus. a third dehydrin-like gene, dprc, was detected in the genome of the filamentous fungus and repressed during conidial germination. the deletion mutant was impaired in freezing tolerance. the dprc-mediated response was dependent on the saka map kinase pathway, and accordingly, saka phosphorylation was induced by cold shock. when fused to egfp, ...201222306917
[huge aspergilloma developed within a zone of scleroderma-related pulmonary fibrosis].in pulmonary aspergilloma, aspergillus colonizes and proliferates as a saprophyte in deterged cavities deprived of local defense. although pulmonary tuberculosis constitutes the one well-know predisposing factor, other causes can create favorable conditions. we describe a first published case of a huge aspergilloma which developed within a zone of pulmonary fibrosis secondary to systemic scleroderma. the patient was a 58-year-old woman in poor general health who experienced repeated episodes of ...201122305135
trichostatin a abrogates airway constriction, but not inflammation, in murine and human asthma models.histone deacetylase (hdac) inhibitors may offer novel approaches in the treatment of asthma. we postulate that trichostatin a (tsa), a class 1 and 2 inhibitor of hdac, inhibits airway hyperresponsiveness in antigen-challenged mice. mice were sensitized and challenged with aspergillus fumigatus antigen (af) and treated with tsa, dexamethasone, or vehicle. lung resistance (r(l)) and dynamic compliance were measured, and bronchial alveolar lavage fluid (balf) was analyzed for numbers of leukocytes ...201222298527
crystal structures and small-angle x-ray scattering analysis of udp-galactopyranose mutase from the pathogenic fungus aspergillus fumigatus.udp-galactopyranose mutase (ugm) is a flavoenzyme that catalyzes the conversion of udp-galactopyranose to udp-galactofuranose, which is a central reaction in galactofuranose biosynthesis. galactofuranose has never been found in humans but is an essential building block of the cell wall and extracellular matrix of many bacteria, fungi, and protozoa. the importance of ugm for the viability of many pathogens and its absence in humans make ugm a potential drug target. here we report the first crysta ...201222294687
[triple fungal infection in a patient with liver cirrhosis].the prevalence of invasive mycoses is increasing, especially among patients who are immunocompromised or hospitalized with serious underlying diseases. such infections are associated with a high morbidity and significant mortality, requiring early diagnosis and appropriate treatment but also an optimal prophylaxis in patients with high risk factors. we report a case of triple fungal infection including an invasive pulmonary aspergillosis by aspergillus fumigatus, a candidemia by candida albicans ...201222294141
fetuin a, a serum component, promotes growth and biofilm formation by aspergillus fumigatus.aspergillus fumigatus is an all-important pathogenic fungus and is known for its angiotropism. when it invades human organs, a. fumigatus makes direct contact with blood and its components by causing inflammation and invading vascular structures. to learn the effect of its contact with blood on the development of infection, we examined the effect of serum on a. fumigatus growth. in dulbecco's modified eagle's medium containing 10% fetal bovine serum, hyphal tip growth was accelerated, forming a ...201222293034
nce102 homologue in aspergillus fumigatus is required for normal sporulation, not hyphal growth or pathogenesis.in saccharomyces cerevisiae, nce102 encodes a 173 amino acid transmembrane protein, which acts as a key player in eisosome assembly and plasma membrane organization. here, we describe the characterization of nce102 homologue in the human pathogen, aspergillus fumigatus. our results demonstrated that afunce102 is continuously expressed during fungal growth. in addition, microscopic examination of an afunce102-gfp-expressing transformant confirmed the localization of the fusion protein to the endo ...201222289033
a sheep model to investigate the role of fungal biofilms in sinusitis: fungal and bacterial synergy.the role of fungi in the spectrum of chronic rhinosinusitis (crs) is poorly understood. fungal biofilms have recently been discovered in crs patients. we have developed an animal model for the investigation of sinonasal fungal biofilms. the role of type i hypersensitivity and pathogenic bacteria is presented.201122287463
human sinonasal epithelial cells direct dendritic function and t-cell t helper 1/t helper 2 skewing following aspergillus exposure.in lower airway disease such as asthma, epithelial cells have been shown to be potent regulators of dendritic cell (dc) functions. however, it is unclear how human sinonasal epithelial cells (hsnecs) from patients with sinusitis regulate dc functions. therefore, in these studies we investigated the ability of aspergillus fumigatus exposed hsnecs to regulate dc antigen uptake, maturation, and direction of t-cell t helper 1 (th1)/th2 skewing.201122287430
duality of liver and kidney lesions after systemic infection of immunosuppressed and immunocompetent mice with aspergillus fumigatus.invasive aspergillosis is a life-threatening disease mainly caused by aspergillus fumigatus. patients at risk are generally immunocompromised and lungs are assumed to provide the primary site for infection and invasive disease manifestation. contrarily, visceral organ involvement appears to result from a subsequent hematogenous spread. to compare the kinetics of dissemination within deep organs in immunosuppressed vs. immunocompetent mice, we used a bioluminescent a. fumigatus strain in an intra ...201222286702
surface display of gaussia princeps luciferase allows sensitive fungal pathogen detection during cutaneous aspergillosis.non-invasive imaging techniques in microbial disease models have delivered valuable insights in the intimate pathogen-host interplay during infection. here we describe evaluation and validation of a transgenic bioluminescence reporter strain of the human-pathogenic mold aspergillus fumigatus, one of the main fungal pathogens affecting immunocompromised individuals. expression and surface display of the gaussia princeps luciferase allowed sensitive and rapid detection of luminescence emitted from ...201222286700
shedding natural light on fungal infections.bioluminescence imaging allows the visualization of the temporal and spatial progression of biological phenomena, in particular infection, by non-invasive methods in vivo. this nature-borrowed technology has been successfully used to monitor bacterial infections but recent studies have also succeeded in tracking fungal infections such as those caused by the two major opportunistic fungal pathogens candida albicans and aspergillus fumigatus. the findings of donat and collaborators published in th ...201222286695
fungi and allergic lower respiratory tract diseases.asthma is a common disorder that in 2009 afflicted 8.2% of adults and children, 24.6 million persons, in the united states. in patients with moderate and severe persistent asthma, there is significantly increased morbidity, use of health care support, and health care costs. epidemiologic studies in the united states and europe have associated mold sensitivity, particularly to alternaria alternata and cladosporium herbarum, with the development, persistence, and severity of asthma. in addition, s ...201222284927
functional analysis is a paramount prerequisite for understanding the in vitro interaction of human natural killer cells with aspergillus fumigatus. 201222279122
a novel cybb mutation with the first genetically confirmed case of chronic granulomatous disease in south africa.a case of a child with chronic granulomatous disease (cgd) presenting with recurrent mycobacterial infections and invasive aspergillus fumigatus disease is described. genetic analysis confirmed x-linked cgd with a novel mutation in exon 10 of the cybb gene - the first south african report of genetically confirmed cgd.201122272860
lesson of the month (2). an unique presentation of infective endocarditis.this lesson reports the case of endophthalmitis, a rare presentation of infective endocarditis (ie), two months following cardiac surgery. although inflammatory markers were increased, blood cultures were negative. transoesophageal echocardiography demonstrated an aortic root abscess. culture of tissue obtained at surgery revealed the infective organism to be aspergillus fumigatus, a rare cause of ie in the immunocompetent patient.201122268325
anesthesia and perioperative management of a pneumonectomized dog.although left- or right-sided pneumonectomy is tolerated by normal dogs, complications impacting the respiratory, cardiovascular, and gastrointestinal systems are not uncommon. pneumonectomy in dogs results in secondary changes in the remaining lung, which include: decreased compliance and vital capacity; and increased pulmonary vascular resistance potentially leading to right ventricular hypertrophy. such alterations make the anesthetic management of an animal with one lung particularly challen ...201222267172
rt-qpcr detection of aspergillus fumigatus rna in vitro and in a murine model of invasive aspergillosis utilizing the paxgene(®) and tempus™ rna stabilization systems.molecular diagnosis of invasive aspergillosis (ia) is a potentially life-saving tool in the care of at-risk individuals. to date, the development of pcr-based diagnostic tests has been hampered by the lack of standardization in the methods for such critical activities. in this study, we used both spiked volunteer blood samples and a murine model of ia to test the utility of the paxgene and tempus systems for stabilization and isolation of fungal rna from blood as part of an evaluation of a new d ...201222263641
concentrations and diversity of microbes from four local bioaerosol emission sources in finland.microbial particles can readily be released into the air from different types of man-made sources such as waste operations. microbiological emissions from different biological sources and their dispersion may be an issue of concern for area planning and for nearby residents. this study was designed to determine the concentrations and diversity of microbiological emissions from four different man-made source environments: waste center with composting windrows, sewage treatment plant, farming envi ...201122263426
hypersensitivity testing for aspergillus fumigatus ige is significantly more sensitive than testing for aspergillus niger ige.we sought to determine if sufficient redundancy exists between specific ige testing for aspergillus fumigatus and aspergillus niger to eliminate one of the assays in determining aspergillus hypersensitivity. we reviewed regional laboratory results comparing a fumigatus-specific ige with a niger-specific ige using the pharmacia unicap system (pharmacia, kalamazoo, mi). by using the fisher exact test as an index of concordance among paired results, we showed a significant difference between 109 pa ...201222261444
regulatory interactionis for iron homoeostatis in aspergillus fumigatus inferred by a systems biology approach.abstract: background: in system biology, iterations of wet-lab experiments followed by modelling approaches and model-inspired experiments describe a cyclic workflow. this approach is especially useful for the inference of gene regulatory networks based on high-throughput gene expression data. experiments can verify or falsify the predicted interactions allowing further refinement of the network model. aspergillus fumigatus is a major human fungal pathogen. one important virulence trait is its ...201222260221
il-17 drives pulmonary eosinophilia following repeated aspergillus fumigatus conidia exposure.previous research in our laboratory has demonstrated that repeated intranasal exposure to aspergillus fumigatus conidia in c57bl/6 mice results in a chronic pulmonary inflammatory response that reaches maximal after four challenges. the inflammatory response is characterized by eosinophilia, goblet cell metaplasia, and t(h)2 cytokine production, which is accompanied by sustained il-17 expression that persists even after the t(h)2 response has begun to resolve. t(h)17 cells could develop in mice ...201222252873
small surfactant-like peptides can drive soluble proteins into active aggregates.inactive protein inclusion bodies occur commonly in escherichia coli (e. coli) cells expressing heterologous proteins. previously several independent groups have found that active protein aggregates or pseudo inclusion bodies can be induced by a fusion partner such as a cellulose binding domain from clostridium cellulovorans (cbdclos) when expressed in e. coli. more recently we further showed that a short amphipathic helical octadecapeptide 18a (ewlkafyekvleklkelf) and a short beta structure pep ...201222251949
immunoproteomics based identification of thioredoxin reductase glit and novel aspergillus fumigatus antigens for serologic diagnosis of invasive aspergillosis.abstract: background: there has been a rising incidence of invasive aspergillosis (ia) in critically ill patients, even in the absence of an apparent predisposing immunodeciency. the diagnosis of ia is difficult because clinical signs are not sensitive and specific, and serum galactomannan has relatively low sensitivity in this group of patients. therefore, more prompt and accurate disease markers for early diagnosis are needed. to establish disease markers demands a thorough knowledge of funga ...201222251604
interlaboratory comparison of pcr-based identification of candida and aspergillus dna in spiked blood samples.despite pcr per se being a powerful and sensitive technique, regarding the detection of fungi in patients' blood, no consensus for a standardised pcr protocol yet exists. to complement other ongoing or accomplished studies which tackle this problem, the german reference center for systemic mycoses conducted an interlaboratory comparison starting with blood samples spiked with fungal cell elements. altogether, six laboratories using in-house pcr-protocols from germany and austria participated in ...201222248125
synthesis and anti-microbial screening of novel schiff bases of 3-amino-2-methyl quinazolin 4-(3h)-one.in the present study, novel schiff bases were synthesized by condensation of 3-amino-2-methyl quinazolin-4-(3h)-ones with different aromatic aldehydes. the 3-amino-2-methyl quinazolin-4-(3h)-one was synthesized from anthranilic acid via the 2-methyl benzoxazin-4-one. the chemical structures of the synthesized compounds were confirmed by means of infrared (ir), (1)h-nmr, (13)c-nmr, mass spectral, and elemental analysis. these compounds were screened for anti-bacterial (staphylococcus aureus atcc ...201022247864
how does antifungal pharmacology differ for mucormycosis versus aspergillosis?over the last decade, advances in diagnostic systems and the introduction of new antifungal agents have significantly improved outcomes in immunocompromised patients who develop invasive aspergillosis. however, mortality rates remain relatively unchanged for less common, but highly aggressive, mold infections such as mucormycosis. recent genome sequencing of rhizopus oryzae revealed evidence of a whole-genome duplication event during the evolution of this pathogen. consequently, r. oryzae has a ...201222247448
outbreak of invasive aspergillosis after major heart surgery caused by spores in the air of the intensive care unit.outbreaks of invasive aspergillosis (ia) are believed to be caused by airborne aspergillus conidia. few studies have established a correlation between high levels of aspergillus fumigatus conidia and the appearance of new cases of ia or have demonstrated matching genotypes between clinical isolates and those from the environment.201222247307
resistin-like molecule-α regulates il-13-induced chemokine production but not allergen-induced airway responses.resistin-like molecule α (relm-α) is one of the most up-regulated gene products in allergen- and parasite-associated th2 responses. localized to alternatively activated macrophages, relm-α was shown to exert an anti-inflammatory effect in parasite-induced th2 responses, but its role in experimental asthma remains unexplored. here, we analyzed the cellular source, the il-4 receptors required to stimulate relm-α production, and the role of relm-α after experimental asthma induction by il-4, il-13, ...201222246861
trivalent ultrashort lipopeptides are potent ph dependent antifungal agents.the activity of antimicrobial peptides (amps) that contain a large proportion of histidine residues (pk(a) ∼ 6) depends on the physiological ph environment. advantages of these amps include high activity in slightly acidic areas of the human body and relatively low toxicity in other areas. also, many amps are highly active in a multivalent form, but this often increases toxicity. here we designed ph dependent amphiphilic compounds consisting of multiple ultrashort histidine lipopeptides on a tri ...201222243686
refurbishment works in a hospital during normal operation.background: construction and renovation work in hospitals pose risks of fungal airborne infections for immunosuppressed patients. if possible, reconstruction work will be postponed to periods without patient treatment. however, in many situations urgent damage demands immediate refurbishment works before the transferring of patients to other wards or closure of wards is possible. reported here are infection control related measures and implemented procedures after two incidents of water damage w ...201122242092
prophylactic efficacy of single dose pulmonary administration of amphotericin b inhalation powder in a guinea pig model of invasive pulmonary aspergillosis.amphotericin b inhalation powder (abip) is a novel dry-powder amphotericin b formulation that is directly delivered to the lung, resulting in elevated lung tissue drug concentrations of this polyene. we evaluated the prophylactic efficacy of single dose administration of abip in a guinea pig model of invasive pulmonary aspergillosis.201222240402
characterization and application of fusidane antibiotic biosynethsis enzyme 3-ketosteroid-∆(1)-dehydrogenase in steroid transformation.microbial ∆ ( 1 ) -dehydrogenation is one of the most important transformations in the synthesis of steroid hormones. in this study, a 3-ketosteroid-∆(1)-dehydrogenase (kstd(f)) involved in fusidane antibiotic biosynthesis from aspergillus fumigatus cicc 40167 was characterized for use in steroid transformation. kstd(f) encodes a polypeptide consisting of 637 amino acid residues. it shows 51% amino acid identi ...201222234537
a new approach to drug discovery: high-throughput screening of microbial natural extracts against aspergillus fumigatus using resazurin.natural products are an inexhaustible source for drug discovery. however, the validation and selection of primary screening assays are vital to guarantee a selection of extracts or molecules with relevant pharmacological action and worthy of following up. the assay must be rapid, simple, easy to implement, and produce quick results and preferably at a low cost. in this work, we developed and validated a colorimetric microtiter assay using the resazurin viability dye. the parameters of the resazu ...201222233645
biomedically important pathogenic fungi detection with volatile biomarkers.volatile chemical profiles collected from the headspace of aspergillus fumigatus (a pathogenic fungus that causes invasive pulmonary aspergillosis, allergic bronchopulmonary aspergillosis and chronic fungal sinusitis) grown on media with the connective tissue protein elastin, found in lung tissue, contained a large abundance of the sesquiterpene farnesene (3,7,11-trimethyl-1,3,6,10-dodecatetraene) and, depending on extraction time and sorbent material, other farnesene isomers and sesquiterpenes ...201222233561
analysis of gene expression in canine sino-nasal aspergillosis and idiopathic lymphoplasmacytic rhinitis: a transcriptomic analysis.sino-nasal aspergillosis (sna) and lymphoplasmacytic rhinitis (lpr) are two common causes of nasal discharge in dog. sna is typically due to an invasion of aspergillus fumigatus in the surface of nasal mucosa. the etiology of lpr is poorly understood and a possible implication of fungi is suspected. the purpose of the present study was to explore the immunopathogenesis of these diseases by comparing gene expression in the nasal mucosa from dogs affected by sna or lpr with healthy dogs, using a c ...201122221380
role of oregano (origanum vulgare) essential oil as a surface fungus inhibitor on fermented sausages: evaluation of its effect on microbial and physicochemical characteristics.oregano essential oil (oeo) was evaluated to determine its effect on the growth of natural contaminating molds on the surface of spanish fermented sausage, the development of the internal microbial population of the sausage, and the physicochemical properties of the sausage. results indicated a dramatic reduction in the contaminant molds. at the end of ripening, the main endogenous fungal species in control samples were mucor racemosus (55%), aspergillus fumigatus (20.6%), cladosporium sphaeros ...201222221361
deciphering cell wall integrity signalling in aspergillus fumigatus: identification and functional characterization of cell wall stress sensors and relevant rho gtpases.the fungal cell wall, a conserved and highly dynamic structure, is essential for virulence and viability of fungal pathogens and is an important antifungal drug target. the cell wall integrity (cwi) signalling pathway regulates shape and biosynthesis of the cell wall. in this work we identified, localized and functionally characterized four putative cwi stress sensors of aspergillus fumigatus, an airborne opportunistic human pathogen and the cause of invasive aspergillosis. we show that wsc1 is ...201222220813
a water-damaged home and health of occupants: a case study.a family of five and pet dog who rented a water-damaged home and developed multiple health problems. the home was analyzed for species of mold and bacteria. the diagnostics included mri for chronic sinusitis with ent and sinus surgery, and neurological testing for neurocognitive deficits. bulk samples from the home, tissue from the sinuses, urine, nasal secretions, placenta, umbilical cord, and breast milk were tested for the presence of trichothecenes, aflatoxins, and ochratoxin a. the family h ...201122220187
the relevance of the migration inhibitory factor (mif) for peripheral tissue response in murine sublethal systemic aspergillus fumigatus infection.we recently demonstrated that macrophage migration inhibitory factor deficient (mif (- / -)) mice exhibited a higher susceptibility to lethal systemic aspergillus fumigatus infections than genetically matched, wild-type (wt) c57bl/6 mice, and displayed altered cytokine profiles in the spleen when challenged by sublethal infections. in this report we focused on the potential involvement of mif in the response of mice to sublethal systemic a. fumigatus infections in tissues other than spleen. impa ...201222217210
ctbt (7-chlorotetrazolo[5,1-c]benzo[1,2,4]triazine) producing ros affects growth and viability of filamentous fungi.ctbt (7-chlorotetrazolo[5,1-c]benzo[1,2,4]triazine) causes intracellular superoxide production and oxidative stress and enhances the susceptibility of saccharomyces cerevisiae, candida albicans, and c. glabrata cells to cycloheximide, 5-fluorocytosine, and azole antimycotic drugs. here, we demonstrate the antifungal activity of ctbt against 14 tested filamentous fungi. ctbt prevented spore germination and mycelial proliferation of aspergillus niger and the pathogenic aspergillus fumigatus. the a ...201222212016
reshuffling of aspergillus fumigatus cell wall components chitin and β-glucan under influence of caspofungin and nikkomycin z alone or in combination.chitin and β-glucan are major cell wall components of aspergillus spp. we investigated the antifungal activity of chitin synthesis inhibitors nikkomycin z, polyoxin d, flufenoxuron, lufenuron and teflubenzuron, alone and combined with β-glucan synthesis inhibitor caspofungin. only nikkomycin z and caspofungin were found to act synergistically. the nikkomycin z-induced chitin decrease corresponded with a β-glucan increase, while with the caspofungin-induced β-glucan decrease, an increase in chiti ...201122203603
indoor exposure to mould allergens.humid indoor environments may be colonised by allergenic filamentous microfungi (moulds), aspergillus spp., penicillium spp., cladosporium spp., and alternaria spp. in particular. mould-induced respiratory diseases are a worldwide problem. in the last two decades, mould allergens and glucans have been used as markers of indoor exposure to moulds. recently, mould allergens alt a 1 (alternaria alternata) and asp f 1 (aspergillus fumigatus) have been analysed in various environments (residential an ...201122202471
sp-a and sp-d in host defense against fungal infections and allergies.innate immunity mediated by pattern recognition proteins is relevant in the host defense against fungi. sp-a and sp-d are two such proteins belonging to the class of collagen domain containing c-type lectins, or collectins. they bind to the sugar moieties present on the cell walls of various fungi in a dose dependent manner via their carbohydrate recognition domain (crd). sp-a and sp-d directly interact with alveolar macrophages, neutrophils, lymphocytes. we review these roles of sp-a and sp-d a ...201222201901
nocardia brain abscess in a liver transplant recipient.nocardia brain abscess is rare. we report on a unique case of n. farcinica brain abscess in a liver transplant recipient, following aspergillus fumigatus pneumonia. a 43-year-old liver transplant recipient presented with altered mentality at 2 months after a. fumigates pneumonia. he was successfully treated with surgical removal and antibiotic therapy with trimethoprim-sulfamethoxazole and ceftriaxone.201122200027
antifungal drug resistance: mechanisms, epidemiology, and consequences for treatment.antifungal resistance continues to grow and evolve and complicate patient management, despite the introduction of new antifungal agents. in vitro susceptibility testing is often used to select agents with likely activity for a given infection, but perhaps its most important use is in identifying agents that will not work, i.e., to detect resistance. standardized methods for reliable in vitro antifungal susceptibility testing are now available from the clinical and laboratory standards institute ...201222196207
detection and measurement of fungal burden in a guinea pig model of invasive pulmonary aspergillosis by novel quantitative nested real-time pcr compared with galactomannan and (1,3)-β-d-glucan detection.we developed and assessed the diagnostic value of a novel quantitative nested real-time pcr (qnrt) assay targeting the internal-transcribed (its) region of ribosomal dna (rdna) in a guinea pig model of invasive pulmonary aspergillosis. groups of 5 immunosuppressed animals that were infected using an aerosol chamber with a. fumigatus conidia were humanely terminated 1 hour post-inoculation and at days 3, 5, 7 and 11 post challenge, and lung tissue, bronchoalveolar lavage fluid (bal), whole blood ...201122189110
[allergic bronchopulmonary aspergillosis mimicking lung cancer in patients without bronchial asthma - case report.]allergic bronchopulmonary aspergillosis (abpa) is a pulmonary disorder characterized by hypersensitivity reaction to aspergillus, mainly aspergillus fumigatus with variable radiological findings. the prevalence of abpa is about 1-2% in patients with asthma and 5-15% in patients with cystic fibrosis. very infrequently the disease is diagnosed in patients without previous bronchial asthma. the case of 45 year old women has been shown, who was admitted to the hospital with suspicious of lung ca ...201222187181
synthesis and biological evaluation of some thiazolidinones as antimicrobial agents.a novel series of thiazolidinone derivatives namely 4-(4-dimethylamino-6-{4-[5-(4-ethylpiperazin-1-ylmethyl)-4-oxo-2-phenylthiazolidin-3-yl]-phenylamino}-[1,3,5]triazin-2-yloxy)-1-methyl-1h-quinolin-2-one have been synthesized from the key intermediate 4-[4-(4-aminophenylamino)-6-dimethylamino-[1,3,5]triazin-2-yloxy]-1-methyl-1h-quinolin-2-one (7). condensation reaction of compound 7 with different aldehyde derivatives were performed to obtain schiff base derivatives, which after cyclization gav ...201122182927
Systemic FasL neutralization increases eosinophilic inflammation in a mouse model of asthma.BACKGROUND: Eosinophils and lymphocytes are pathogenically important in allergic inflammation and sensitive to Fas-mediated apoptosis. Fas ligand (FasL) activity therefore should play a role in regulating the allergic immune response. We aimed to characterize the role of FasL expression in airway eosinophilia in Aspergillus fumigatus (Af)-induced sensitization and to determine whether FasL neutralization alters the inflammatory response. METHODS: Sensitized Balb/c mice were killed before (day 0) ...201122175699
In vitro and in vivo evaluation of selected (68)Ga-siderophores for infection imaging.INTRODUCTION: Siderophores are low-molecular-mass iron chelators serving as iron transporters for almost all bacteria, fungi and some plants. Iron is an essential element for majority of organisms and plays an important role in virulence of pathogenic organisms. (68)Ga is a positron emitter with complexing properties comparable to those of Fe(III) and readily available from a generator. Initial studies with (68)Ga-triacetylfusarinine C (TAFC) showed excellent targeting properties in a rat infect ...201122172389
Evaluation of a Recombinant Antigen-Based EIA for the Diagnosis of Non-Invasive Aspergillosis.Antibody detection is a key diagnostic tool for non-invasive aspergillosis (NIA) such as allergic broncho-pulmonary aspergillosis and chronic pulmonary aspergillosis. Specific immuno-precipitins detection (IPD) is considered as the reference but lacks standardization and is time-consuming. To evaluate the performance of a new anti-Aspergillus fumigatus IgG enzyme immunoassay (EIA) kit using a recombinant A. fumigatus antigen (Bio-Rad), a retrospective study was performed on 551 sera collected fr ...201122170901
structural analysis of fungal cerebrosides.of the ceramide monohexosides (cmhs), gluco- and galactosyl-ceramides are the main neutral glycosphingolipids expressed in fungal cells. their structural determination is greatly dependent on the use of mass spectrometric techniques, including fast atom bombardment-mass spectrometry, electrospray ionization, and energy collision-induced dissociation mass spectrometry. nuclear magnetic resonance has also been used successfully. such a combination of techniques, combined with classical analytical ...201122164155
impact of the lectin chaperone calnexin on the stress response, virulence and proteolytic secretome of the fungal pathogen aspergillus fumigatus.calnexin is a membrane-bound lectin chaperone in the endoplasmic reticulum (er) that is part of a quality control system that promotes the accurate folding of glycoproteins entering the secretory pathway. we have previously shown that er homeostasis is important for virulence of the human fungal pathogen aspergillus fumigatus, but the contribution of calnexin has not been explored. here, we determined the extent to which a. fumigatus relies on calnexin for growth under conditions of environmenta ...201122163332
Role of NADPH Oxidase versus Neutrophil Proteases in Antimicrobial Host Defense.NADPH oxidase is a crucial enzyme in mediating antimicrobial host defense and in regulating inflammation. Patients with chronic granulomatous disease, an inherited disorder of NADPH oxidase in which phagocytes are defective in generation of reactive oxidant intermediates (ROIs), suffer from life-threatening bacterial and fungal infections. The mechanisms by which NADPH oxidase mediate host defense are unclear. In addition to ROI generation, neutrophil NADPH oxidase activation is linked to the re ...201122163282
high-level expression and characterization of a highly thermostable chitosanase from aspergillus fumigatus in pichia pastoris.the sequence of an endo-chitosanase gene (csn) from aspergillus fumigatus was optimized based on the preferred codons of pichia pastoris and synthesized in vitro through overlapping pcr (csn-p). the gene was cloned into a yeast expression vector, phbm905a, and secretorily expressed in pichia pastoris gs115. the yield of csn-p reached ~3 mg/ml with a high-density fermentation in a 14 l fermenter and the enzyme activity was ~25,000 u/ml. the enzyme had half-lives of 2.5 h at 80°c, 1 h at 90°c and ...201122160328
post-translational modifications of proteins in the pathobiology of medically relevant fungi.post-translational modifications of proteins drive a wide variety of cellular processes in eukaryotes, regulating cell growth and division as well as adaptive and developmental processes. with regard to the fungal kingdom, most information about post-translational modifications has been generated through studies of the model yeasts saccharomyces cerevisiae and schizosaccharomyces pombe, where for example, the roles of protein phosphorylation, glycosylation, acetylation, ubiquitination, sumoylati ...201122158711
transcription of pattern recognition receptors and abortive agents induced chemokines in the bovine pregnant uterus.pattern recognition receptors (prrs) are important components of the innate immune system whose ligands are specific pathogen associated molecular patterns (pamps). considering the scarcity of studies on transcription of prrs in the pregnant uterus of cows, and its response to pamps and microorganisms that cause abortion in cattle, this study aimed to characterize the transcription of tlr1-10, nod1, nod2 and md2 in bovine uterus throughout gestation and to investigate the sensitivity of differen ...201122153993
Contribution of a Cyclonic-Based Liquid Air Collector for Detecting Aspergillus Fumigatus by QPCR in Air Samples. 201222150297
tlr3 essentially promotes protective class i-restricted memory cd8+ t-cell responses to aspergillus fumigatus in hematopoietic transplanted patients.aspergillus fumigatus is a model fungal pathogen and a common cause of severe infections and diseases. cd8(+) t cells are present in the human and murine t cell repertoire to the fungus. however, cd8(+) t cell function in infection as well as the molecular mechanisms that control their priming and differentiation into effector and memory cells in vivo remains elusive. in this study, we report that both cd4(+) and cd8(+) t cells mediate protective memory responses to the fungus contingent upon th ...201122147891
srebp coordinates iron and ergosterol homeostasis to mediate triazole drug and hypoxia responses in the human fungal pathogen aspergillus fumigatus.sterol regulatory element binding proteins (srebps) are a class of basic helix-loop-helix transcription factors that regulate diverse cellular responses in eukaryotes. adding to the recognized importance of srebps in human health, srebps in the human fungal pathogens cryptococcus neoformans and aspergillus fumigatus are required for fungal virulence and susceptibility to triazole antifungal drugs. to date, the exact mechanism(s) behind the role of srebp in these observed phenotypes is not clear. ...201122144905
E1210, a New Broad-Spectrum Antifungal, Suppresses Candida albicans Hyphal Growth through Inhibition of Glycosylphosphatidylinositol Biosynthesis.Continued research towards the development of new antifungals that act via inhibition of glycosylphosphatidylinositol (GPI) biosynthesis led to the design of E1210. In this study, we assessed the selectivity of the inhibitory activity of E1210 against Candida albicans GWT1 (Orf19.6884) protein, Aspergillus fumigatus GWT1 (AFUA_1G14870) protein, and human PIG-W proteins that could catalyze the inositol acylation of GPI early in the GPI biosynthesis pathway, and then assessed the effects of E1210 ...201122143530
recurrent aspergillus contamination in a biomedical research facility: a case study.fungal contamination of biomedical processes and facilities can result in major revenue loss and product delay. a biomedical research facility (brf) culturing human cell lines experienced recurring fungal contamination of clean room incubators over a 3-year period. in 2010, as part of the plan to mitigate contamination, 20 fungal specimens were isolated by air and swab samples at various locations within the brf. aspergillus niger and aspergillus fumigatus were isolated from several clean-room i ...201122143434
aspergillosis in gamebirds and ducks. 201122141128
CFTR Regulates Epithelial Cell Response to Aspergillus and Resultant Pulmonary Inflammation.RATIONALE: Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) alter epithelial cell (EC) interactions with multiple microbes, such that dysregulated inflammation and injury occur with airway colonization in people with cystic fibrosis (CF). Aspergillus fumigatus frequently colonizes CF airways, but it has been assumed to be an innocent saprophyte; its potential role as a cause of lung disease is controversial. OBJECTIVES: To study the interactions between Aspergillus ...201122135344
luminescent-activated transfected killer cells to monitor leukocyte trafficking during systemic bacterial and fungal infection.background. activated transfected killer (atak) cells are immortal phagocytes transfected with a luminescence reporter that effectively treat lethal infections in neutropenic mice. their in vivo trafficking, lifespan, and immunogenicity are unknown. methods. mice were made neutropenic; infected or not with staphylococcus aureus, acinetobacter baumannii, candida albicans, or aspergillus fumigatus; and treated intraperitoneally with atak cells. cell trafficking and lifespan were assessed by in viv ...201222124127
high prevalence of azole-resistant aspergillus fumigatus in adults with cystic fibrosis exposed to itraconazole.aspergillus fumigatus is the most frequent fungus found in the sputum of cystic fibrosis (cf) subjects. itraconazole is prescribed for allergic bronchopulmonary aspergillosis (abpa) or aspergillus bronchitis in cf subjects. we hypothesized that a. fumigatus isolates in the sputum of cf subjects with previous exposure to itraconazole was associated with higher prevalence of azole resistance. from june 2010 to april 2011, sputum samples from adult cf subjects at cochin university hospital (france) ...201122123701
Application of bioluminescence imaging for in vivo monitoring of fungal infections.Fungi can cause severe invasive infections especially in the immunocompromised host. Patient populations at risk are increasing due to ongoing developments in cancer treatment and transplantation medicine. Only limited diagnostic tools and few antifungals are available, rendering a significant number of invasive fungal infections life threatening. To reduce mortality rates, a better understanding of the infection processes is urgently required. Bioluminescence imaging (BLI) is a powerful tool fo ...201222121368
Hyphal growth in human fungal pathogens and its role in virulence.Most of the fungal species that infect humans can grow in more than one morphological form but only a subset of pathogens produce filamentous hyphae during the infection process. This subset is phylogenetically unrelated and includes the commonly carried yeasts, Candida albicans, C. dubliniensis, and Malassezia spp., and the acquired pathogens, Aspergillus fumigatus and dermatophytes such as Trichophyton rubrum and T. mentagrophytes. The primary function of hypha formation in these opportunistic ...201222121367
Production of prostaglandins, isoprostanes and thromboxane by Aspergillus fumigatus: Identification by gas chromatography-tandem mass spectrometry and quantification by enzyme immunoassay.Aspergillus fumigatus has been reported to produce prostaglandin (PG)-like substances. The molecular structure of these fungal eicosanoids is however still unknown. By using the gas chromatography-tandem mass spectrometry (GC-MS/MS) methodology we identified a number of eicosanoids that were formed upon incubation of the precursor arachidonic acid ethyl ester (AAE, 10µM) with three strains of A. fumigatus. The eicosanoids identified include the prostaglandins (PG) PGE(2), 6-keto-PGF(1a) (the sta ...201222118804
Medium optimization for enhanced co-production of two bioactive metabolites in the same fermentation by a statistical approach.This paper describes improved optimization method that combines the one-factor-at-a-time method (OFAT), Plackett-Burman design, and the response surface method (RSM), which were used to optimize the medium for the production of fumigaclavine C (FC) and helvolic acid (HA) from endophytic Aspergillus fumigatus CY018 simultaneously. The ideal carbon and nitrogen sources for the two compounds were assessed initially via the one-factor-at-a-time method. Three key cultivation factors (pH, phosphate, a ...201122115035
[Invasive aspergillosis with extrapulmonary involvement: pathogenesis, clinical characteristics and prognosis.]BACKGROUND: The incidence of invasive aspergillosis has increased worldwide. Information regarding the clinical characteristics of patients with extrapulmonary involvement is scarce. OBJECTIVE: We aimed to describe the pathogenesis, characteristics and outcomes of patients with invasive aspergillosis and extrapulmonary disease. METHODS: A retrospective study conducted in a university hospital in Barcelona, Spain (1995-2011). RESULTS: A total of 12 cases of invasive aspergillosis and extrapulmona ...201122108606
identification and characterization of an aspergillus fumigatus "supermater" pair.the mating efficiency of 50 aspergillus fumigatus isolates from both clinical and environmental sources was analyzed. forty isolates completed the sexual cycle in 4 weeks with variable levels of fertility designated high, medium, or low. two opposite-mating-type strains exhibiting the highest fertility, afb62 (mat1-1), isolated from a case of invasive aspergillosis, and afir928 (mat1-2), isolated from the environment, were chosen as the supermater pair. single cleistothecia obtained from a cross ...201122108383
evidence for genetic differentiation and variable recombination rates among dutch populations of the opportunistic human pathogen aspergillus fumigatus.as the frequency of antifungal drug resistance continues to increase, understanding the genetic structure of fungal populations, where resistant isolates have emerged and spread, is of major importance. aspergillus fumigatus is an ubiquitously distributed fungus and the primary causative agent of invasive aspergillosis (ia), a potentially lethal infection in immunocompromised individuals. in the last few years, an increasing number of a. fumigatus isolates has evolved resistance to triazoles, th ...201222106836
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