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structural insight into the mechanism of oxygen activation and substrate selectivity of flavin-dependent n-hydroxylating monooxygenases.sida from the human pathogen aspergillus fumigatus catalyzes the generation of n(5)-hydroxyornithine in the biosynthesis of siderophores, a reaction essential for virulence. the crystal structures of sida in complex with ornithine and lysine reveal the geometry of the interactions among flavin, nadp(+), and the substrate amine group that underlie the hydroxylation reaction. the structural elucidation of the enzyme in complex with arginine provides insight into the role of electrostatics and hydr ...201222928747
between-laboratory quality control of automated analysis of igg antibodies against aspergillus fumigatus.measurement of igg antibodies against aspergillus fumigatus is an important criterion for the diagnosis of aspergilloma, allergic bronchopulmonary aspergillosis, and extrinsic allergic alveolitis. in the present study, we compared igg antibody analysis against a. fumigatus using 2 widely used automated immunochemistry systems. in a between-laboratory quality control program, good agreement was found between the results from laboratories that used the immunocap system; however, a laboratory that ...201222925654
synthesis, crystal structure, characterisation, and antifungal activity of 3-thiophene aldehyde semicarbazone (3stch), 2,3-thiophene dicarboxaldehyde bis(semicarbazone) (2,3bstch2) and their nickel (ii) complexes.the reaction of nickel (ii) chloride and bromide with 3-thiophene aldehyde semicarbazone (3stch) and 2,3-thiophene dicarboxaldehyde bis(semicarbazone) (2,3bstch(2)) leads to the formation of a series of new complexes: [nicl(2)(3stch)(2)], [nibr(2)(3stch)(2)], [nicl(2,3bstch(2))(h(2)o)]cl, and [nibr(2,3bstch(2))(h(2)o)]br respectively. the crystal structures of the two ligands 3stch, 2,3bstch(2) and of the complex [nibr(2,3bstch(2))(h(2)o)]br have been determined by x-ray diffraction methods. for ...201222922309
a thermostable crude endoglucanase produced by aspergillus fumigatus in a novel solid state fermentation process using isolated free water.aspergillus fumigatus was grown on chopped wheat straw in a solid state fermentation (ssf) process carried out in constant presence of isolated free water inside the fermentation chamber. the system allowed maintaining a constant vapor pressure inside the fermentor throughout the fermentation process. crude endoglucanase produced by a. fumigatus under such conditions was more thermostable than previously reported enzymes of the same fungal strain which were produced under different conditions an ...201222919467
fad2-dgat2 genes coexpressed in endophytic aspergillus fumigatus derived from tung oilseeds.recent efforts to genetically engineer plants that contain fatty acid desaturases to produce valuable fatty acids have made only modest progress. diacylglycerol acyltransferase 2 (dgat2), which catalyzes the final step in triacylglycerol (tag) assembly, might potentially regulate the biosynthesis of desired fatty acids in tags. to study the effects of tung tree (vernicia fordii) vfdgat2 in channeling the desired fatty acids into tag, vfdgat2 combined with the tung tree fatty acid desaturase-2 (v ...201222919314
the antimicrobial, antioxidative, anti-inflammatory activity and cytotoxicity of different fractions of four south african bauhinia species used traditionally to treat diarrhoea.many bauhinia species, including those indigenous to south africa, are used in traditional medicine across the world for treating ailments such as gastrointestinal tract (git) disorders, diabetes, infectious diseases and inflammation.201222917809
zap1 regulates zinc homeostasis and modulates virulence in cryptococcus gattii.zinc homeostasis is essential for fungal growth, as this metal is a critical structural component of several proteins, including transcription factors. the fungal pathogen cryptococcus gattii obtains zinc from the stringent zinc-limiting milieu of the host during the infection process. to characterize the zinc metabolism in c. gattii and its relationship to fungal virulence, the zinc finger protein zap1 was functionally characterized. the c. gattii zap1 gene is an ortholog of the master regulato ...201222916306
comparative genome analysis between aspergillus oryzae strains reveals close relationship between sites of mutation localization and regions of highly divergent genes among aspergillus species.aspergillus oryzae has been utilized for over 1000 years in japan for the production of various traditional foods, and a large number of a. oryzae strains have been isolated and/or selected for the effective fermentation of food ingredients. characteristics of genetic alterations among the strains used are of particular interest in studies of a. oryzae. here, we have sequenced the whole genome of an industrial fungal isolate, a. oryzae rib326, by using a next-generation sequencing system and com ...201222912434
in vivo determination of mouse olfactory mucus cation concentrations in normal and inflammatory states.olfaction is impaired in chronic rhinosinusitis (crs). the study has two aims: (1) to determine whether changes in cation concentration occur in the olfactory mucus of mice with crs, which may affect chemo-electrical transduction, (2) and to examine whether these alterations are physiologically significant in humans.201222911687
the effect of aspergillus fumigatus infection on vitamin d receptor expression in cystic fibrosis.aspergillus fumigatus (a. fumigatus) in cystic fibrosis (cf) is increasingly recognized. although allergic bronchopulmonary aspergillosis (abpa) leads to deterioration of pulmonary function, the effect of a. fumigatus colonization in the absence of abpa remains unclear.201222904183
structural requirements for the activity of the mirb ferrisiderophore transporter of aspergillus fumigatus.siderophores have been identified as virulence factors in the opportunistic fungal pathogen aspergillus fumigatus. the 14-pass transmembrane protein mirb is postulated to function as a siderophore transporter, responsible for uptake of the hydroxamate siderophore n,n',n″-triacetylfusarinine c (tafc). our aim was to identify amino acids of a. fumigatus mirb that are crucial for uptake of tafc. site-directed mutagenesis was used to create mirb mutants. expression of wild-type and mutant proteins i ...201222903978
the aspergillus fumigatus protein glik protects against oxidative stress and is essential for gliotoxin biosynthesis.the function of a number of genes in the gliotoxin biosynthetic cluster (gli) in aspergillus fumigatus remains unknown. here, we demonstrate that glik deletion from two strains of a. fumigatus completely abolished gliotoxin biosynthesis. furthermore, exogenous h(2)o(2) (1 mm), but not gliotoxin, significantly induced a. fumigatus glik expression (p = 0.0101). while both mutants exhibited significant sensitivity to both exogenous gliotoxin (p < 0.001) and h(2)o(2) (p < 0.01), unexpectedly, exogen ...201222903976
clinical epidemiology of 960 patients with invasive aspergillosis from the path alliance registry.the study investigated the epidemiology and outcome of invasive aspergillosis (ia), an important cause of morbidity and mortality in immunocompromised patients.201222898389
in vitro-in vivo correlation of voriconazole resistance due to g448s mutation (cyp51a gene) in aspergillus fumigatus.invasive pulmonary aspergillosis continues to be associated with a high mortality despite timely and appropriate therapy. although host immunity plays a major role in poor clinical response, antifungal drug resistance cannot be ignored. our studies were aimed 1) to study the mechanism of drug resistance in voriconazole strains of aspergillus fumigatus, 2) to establish a causal relationship between cyp51a mutation and voriconazole resistance (vrc-r), and 3) to determine whether vrc-r due to cyp51 ...201222897872
synthesis and antifungal activity of derivatives of 2- and 3-benzofurancarboxylic acids.we found that amiodarone has potent antifungal activity against a broad range of fungi, potentially defining a new class of antimycotics. investigations into its molecular mechanisms showed amiodarone mobilized intracellular ca2+, which is thought to be an important antifungal characteristic of its fungicidal activity. amiodarone is a synthetic drug based on the benzofuran ring system, which is contained in numerous compounds that are both synthetic and isolated from natural sources with antifun ...201222892340
first reported case of azole-resistant aspergillus fumigatus due to the tr/l98h mutation in germany. 201222890769
antimicrobial activity of bioactive compounds and leaf extracts in jatropha tanjorensis.jatropha tanjorensis was investigated scientifically to generate evidence for the efficacies reported in traditional systems and the results are given here.201222884742
characterization of a chitosanase from aspergillus fumigatus atcc13073.chitosanase ii was purified from the culture filtrate of aspergillus fumigatus atcc13073. the purified enzyme had a molecular mass of 23.5 kda. the n-terminal amino acid sequence of chitosanase ii was identical to those of other aspergillus chitosanases belonging to glycoside hydrolase family 75. the optimum ph and temperature were ph 6.0 and 40 °c. chitosanase ii hydrolyzed 70% deacetylated chitosan faster than fully deacetylated chitosan. analysis of the degradation products generated from par ...201222878198
interkingdom metabolic transformations captured by microbial imaging mass spectrometry.in polymicrobial infections, microbes can interact with both the host immune system and one another through direct contact or the secretion of metabolites, affecting disease progression and treatment options. the thick mucus in the lungs of patients with cystic fibrosis is highly susceptible to polymicrobial infections by opportunistic pathogens, including the bacterium pseudomonas aeruginosa and the fungus aspergillus fumigatus. unravelling the hidden molecular interactions within such polymicr ...201222869730
robust polyfunctional t-helper 1 responses to multiple fungal antigens from a cell population generated using an environmental strain of aspergillus fumigatus.aspergillus fumigatus infections are the leading cause of invasive fungal infection-related deaths in stem cell transplant patients, and may be amenable to correction with adoptive immunotherapy providing t lymphocytes specific for a. fumigatus. however, a clinically usable source of antigen and a reliable procedure for the generation of large numbers of aspergillus-specific t lymphocytes to clinical-grade standards is not available.201222866666
multiplexed activity-based protein profiling of the human pathogen aspergillus fumigatus reveals large functional changes upon exposure to human serum.environmental adaptability is critical for survival of the fungal human pathogen aspergillus fumigatus in the immunocompromised host lung. we hypothesized that exposure of the fungal pathogen to human serum would lead to significant alterations to the organism's physiology, including metabolic activity and stress response. shifts in functional pathway and corresponding enzyme reactivity of a. fumigatus upon exposure to the human host may represent much needed prognostic indicators of fungal infe ...201222865858
[pulmonary aspergillosis due to methimazole-induced neutropenia: a case report].a 48-year old woman with a recent diagnosis of graves' disease arrived at the emergency room with fever, palpitations, and a sore throat. her regular treatment included methimazole. on admission, laboratory results showed suppressed tsh, elevated free thyroxine, and neutropenia. she was admitted and started on antibiotics and granulocyte-macrophage colony stimulating factor (gm-csf). after ten days, the patient developed leukocytosis, fever, and hemoptysis. chest ct scan showed a lung cavity wit ...201222858775
aspergillus tanneri sp. nov., a new pathogen that causes invasive disease refractory to antifungal therapy.the most common cause of invasive aspergillosis (ia) in patients with chronic granulomatous disease (cgd) is aspergillus fumigatus followed by a. nidulans; other aspergilli rarely cause the disease. here we review two clinical cases of fatal ia in cgd patients and describe a new etiologic agent of ia refractory to antifungal therapy. unlike typical ia caused by a. fumigatus, the disease caused by the new species was chronic and spread from the lung to multiple adjacent organs. mycological charac ...201222855513
regulation of dendritic cell functions against harmful respiratory pathogens by a cysteinyl leukotrienes receptor antagonist.cysteinyl leukotriene receptor antagonist (ltra) is a widely used medicine for asthma. cysteinyl leukotrienes (cyslts) are involved in the regulation of dendritic cell (dc) function. however, the effects of ltra on dc-related antimicrobial immunity against harmful respiratory pathogens remain unknown. the purpose of this study was to examine the effects of ltra administered in vivo on dc function against representative respiratory pathogens in vitro. pulmonary dcs were isolated from four groups ...201222852127
analysis of promoter function in aspergillus fumigatus.the filamentous fungus aspergillus fumigatus is an important opportunistic pathogen that can cause high mortality levels in susceptible patient populations. the increasing dependence on antifungal drugs to control a. fumigatus has led to the inevitable acquisition of drug-resistant forms of this pathogen. in other fungal pathogens, drug resistance is often associated with an increase in transcription of genes such as atp-binding cassette (abc) transporters that directly lead to tolerance to comm ...201222843562
diversity and specificity of microsatellites within aspergillus section fumigati.microsatellites (or short tandem repeats, strs) are the genetic markers of choice for studying aspergillus fumigatus molecular epidemiology due to its reproducibility and high discrimination power. however, the specificity of these markers must be investigated in a group of isolates from closely related species. the aim of this work was to test a microsatellite-based pcr multiplex previously designed for a. fumigatus in a set of species belonging to section fumigati, namely aspergillus fumigatia ...201222838495
antibodies generated against conserved antigens expressed by bacteria and allergen-bearing fungi suppress airway disease.there has been a sharp rise in allergic asthma and asthma-related deaths in the developed world, in contrast to many childhood illnesses that have been reduced or eliminated. the hygiene hypothesis proposes that excessively sanitary conditions early in life result in autoimmune and allergic phenomena because of a failure of the immune system to receive proper microbial stimulation during development. we demonstrate that abs generated against conserved bacterial polysaccharides are reactive with ...201222837487
interleukin-12 and interleukin-2 alone or in combination against the infection in invasive pulmonary aspergillosis mouse model.aspergillus fumigatus is an intracellular opportunistic fungus causing invasive pulmonary mycosis, characterised by hyphal invasion and destruction of pulmonary tissue. th1 cytokines could enhance fungicidal activity. the effects from the combination of interleukin-12 (il-12) and il-2 are rarely known in invasive pulmonary aspergillosis infection. to assess the cleaning of a. fumigatus infection in the pulmonary tissues by il-12 and il-2, interferon-γ (ifn-γ) was detected in the sera using elisa ...201322834482
assessment of aspergillus sensitization or persistent carriage as a factor in lung function impairment in cystic fibrosis patients.cystic fibrosis (cf) patients presenting with persistent carriage of, or sensitization to, aspergillus fumigatus are often treated with antifungal therapies because the presence of the fungus is commonly thought to impede lung function, even in the absence of allergic bronchopulmonary aspergillosis (abpa). the aim of this study was to assess aspergillus-related status modulating the forced expiratory volume in 1 s (fev₁) of cf patients.201222831545
combination of voriconazole and anidulafungin for treatment of triazole-resistant aspergillus fumigatus in an in vitro model of invasive pulmonary aspergillosis.voriconazole is a first-line agent for the treatment of invasive pulmonary aspergillosis. isolates with elevated voriconazole mics are increasingly being seen, and the optimal treatment regimen is not defined. we investigated whether the combination of voriconazole with anidulafungin may be beneficial for the treatment of a. fumigatus strains with elevated voriconazole mics. we used an in vitro model of the human alveolus to define the exposure-response relationships for a wild-type strain (vori ...201222825124
serum igg responses against aspergillus proteins before hematopoietic stem cell transplantation or chemotherapy identify patients who develop invasive aspergillosis.the ability to identify patients at particularly low risk for invasive aspergillosis (ia) would facilitate more efficient targeting of antifungal prophylaxis. we measured baseline serum immunoglobulin responses against 6 purified recombinant aspergillus fumigatus proteins before hematopoietic stem cell transplantation (hsct) or chemotherapy in 73 subjects, including 19 patients who subsequently developed proven or probable ia and 54 uninfected controls. we also assessed responses at the time of ...201222824184
heat shock protein 90 is required for conidiation and cell wall integrity in aspergillus fumigatus.heat shock protein 90 (hsp90) is a eukaryotic molecular chaperone. its involvement in the resistance of candida albicans to azole and echinocandin antifungals is well established. however, little is known about hsp90's function in the filamentous fungal pathogen aspergillus fumigatus. we investigated the role of hsp90 in a. fumigatus by genetic repression and examined its cellular localization under various stress conditions. failure to generate a deletion strain of hsp90 suggested that it is es ...201222822234
incidence and risk factors for infection in oral cancer patients undergoing different treatments protocols.over the past decade, advances in cancer treatments have been counterbalanced by a rising number of immunosuppressed patients with a multitude of new risk factors for infection. hence, the aim of this study was to determine risk factors, infectious pathogens in blood and oral cavity of oral cancer patients undergoing different treatment procedures.201222817766
comparative analysis of calcineurin signaling between candida dubliniensis and candida albicans.candida dubliniensis, an emerging fungal pathogen, is the closest known species to the established pathogenic species candida albicans. despite the fact that these two species share > 80% genome sequence identity, they exhibit distinct properties such as less hyphal growth, reduced pathogenicity and increased sensitivity to sodium stress and elevated temperatures in c. dubliniensis compared with c. albicans. it is, however, largely unknown whether signaling pathways are conserved in the two cand ...201222808313
a miqe-compliant real-time pcr assay for aspergillus detection.the polymerase chain reaction (pcr) is widely used as a diagnostic tool in clinical laboratories and is particularly effective for detecting and identifying infectious agents for which routine culture and microscopy methods are inadequate. invasive fungal disease (ifd) is a major cause of morbidity and mortality in immunosuppressed patients, and optimal diagnostic criteria are contentious. although pcr-based methods have long been used for the diagnosis of invasive aspergillosis (ia), variable p ...201222808087
isolation of a strain of aspergillus fumigatus able to grow in minimal medium added with an industrial cyanide waste.the present note refers the results about the isolation of an aspergillus fumigatus strain able to grow on an industrial cyanide waste as nitrogen source. the fungus was selected from an alkaline unpolluted soil in enrichment cultures in 50 ml of minimal medium added with 20 mmol glucose and supplemented initially with 0.1 mmol kcn and then with 70 μl of a waste solution from a jewelry industry containing free cyanide and cyanide complexes of heavy metal ions including copper, silver, nickel, an ...201122806792
a novel β-glucosidase from aspergillus fumigates releases diosgenin from spirostanosides of dioscorea zingiberensis c. h. wright (dzw).a β-glucosidase effectively releasing diosgenin from spirostanosides of dioscorea zingiberensis c. h. wright (dzw), named afg, was purified from a strain of aspergillus fumigates. the molecular weight of afg was 113 kda. analysis of protein fragments by esi-q-tof indicated that afg was a β-glucosidase. the circular dichroism spectrum suggested that the main secondary structure of afg in milli-q water was α-helixes. atomic force microscopy revealed that it was a globular protein. afg maintained h ...201122805852
biosynthesis of silver nanoparticles by a new strain of streptomyces sp. compared with aspergillus fumigatus.locally isolated strains of a thermoalkalotolerant streptomyces sp. and aspergillus fumigatus were used for the in vitro biosynthesis of silver nanoparticles from agno(3) solutions. an autolysed cell-free culture filtrate from each strain was used, indicating that the formation mechanism depends on intra-cellular components for both organisms, since culture broths had no significant nanoparticle formation potential. nanoparticle formation was indicated by a change of the solution from colourless ...201122805829
emergence of aspergillus calidoustus infection in the era of posttransplantation azole prophylaxis.universal antifungal prophylaxis with azoles is commonly used after lung transplantation. we noted an increase in isolates of aspergillus calidoustus in our transplant population and hypothesized that increasing azole use (universal prophylaxis since 2008) may be promoting this infection.201222805441
fungicidal activity of lysozyme is inhibited in vitro by commercial sinus irrigation solutions.lysozyme is an innate immune peptide with bactericidal and fungicidal activity (fa). despite increased expression of lysozyme protein in chronic rhinosinusitis (crs) sinus mucosa, crs patients experience repeated bacterial and/or fungal infections. commercial sinus irrigation solutions are often used to provide symptomatic relief. however, one of the mechanisms of action of lysozyme involves ionic interactions with the microbial cell wall, which may be inhibited by ionic solutions such as commer ...201222801018
antidiabetic, anti-oxidant and antimicrobial activities of fadogia ancylantha extracts from malawi.communities in chilumba, malawi use herbal tea prepared from fadogia ancylantha schweinf (rubiaceae) leaves for the management of diabetes, hypertension and alleviation of symptoms of gastrointestinal disorders and pneumonia. the objective of the study was to evaluate the in vitro antidiabetic, anti-oxidant and antimicrobial activities of the crude extracts of the leaves prepared by using three different extraction methods.201222800680
chapter 18: allergic bronchopulmonary aspergillosis.allergic bronchopulmonary aspergillosis (abpa) occurs in patients with asthma or cystic fibrosis resulting in pulmonary infiltrates, tenacious mucus plugs that harbor hyphae of aspergillus fumigatus, elevations of total serum ige concentration and peripheral blood, and sputum eosinophilia. bronchiectasis is an irreversible complication of abpa. the key to early diagnosis is considering abpa in anyone with asthma or cystic fibrosis and a positive skin test to aspergillus and /or recurrent infiltr ...201622794691
a protective mechanism in lungs of rats experimentally infected with aspergillus fumigatus.aspergillus fumigatus is associated with invasive disease aspergillosis in immunocompromised individuals. the major aim of this study was to investigate the biochemical and immunological responses of male wistar rats against a. fumigatus experimentally-induced pulmonary fungal infection. nostril experimental exposure of male wistar rats to a high dose of a. fumigatus freeze-dried preparation for only 24 hr resulted in a significant increase in levels of catalase, nitric oxide and lipid peroxide ...201122783071
fungal aerosol in the process of poultry breeding--quantitative and qualitative analysis.the aim of this study was to assess fungal air contamination in the processes associated with poultry breeding depending on the season. the evaluation was based on the determined concentrations of fungi and qualitative identification of isolated microorganisms.201222774459
interactions of liposome carriers with infectious fungal hyphae reveals the role of β-glucans.relatively little is known about how liposomal formulations modulate drug delivery to fungal pathogens. we compared patterns of hyphal cell wall binding for empty rhodmine-labeled liposomes and the clinically available amphotericin b-containing liposomal formulation (ambisome) in aspergillus fumigatus and candida albicans. following 0.5 h of coincubation with a. fumigatus , empty liposomes concentrated primarily in fungal septae along at the surface of the cell wall, suggesting that liposome upt ...201222770505
aspergillus fumigatus keratitis following intracorneal ring segment implantation.fungal keratitis has been rarely reported following intracorneal ring segment (icrs) inmplantation. this paper aims to report a case of fungal keratitis with aspergillus fumigatus following icrs implantation for correction of keratoconus.201222769849
correlation between triazole treatment history and susceptibility in clinically isolated aspergillus fumigatus.this is the first report of a detailed relationship between triazole treatment history and triazole mics for 154 aspergillus fumigatus clinical isolates. the duration of itraconazole dosage increased as the itraconazole mic increased, and a positive correlation was observed (r = 0.5700, p < 0.0001). the number of itraconazole-naïve isolates dramatically decreased as the itraconazole mic increased, particularly for mics exceeding 2 μg/ml (0.5 μg/ml versus 2 μg/ml, p = 0.03). we also examined the ...201222751542
protein phosphatase z modulates oxidative stress response in fungi.the genome of the filamentous fungus aspergillus nidulans harbors the gene ppza that codes for the catalytic subunit of protein phosphatase z (ppz), and the closely related opportunistic pathogen aspergillus fumigatus encompasses a highly similar ppz gene (phza). when ppza and phza were expressed in saccharomyces cerevisiae or schizosaccharomyces pombe they partially complemented the deleted phosphatases in the ppz1 or the pzh1 mutants, and they also mimicked the effect of ppz1 overexpression in ...201222750657
[azole resistance in aspergillus fumigatus in the netherlands--increase due to environmental fungicides?].the mould aspergillus fumigatus may develop mechanisms that confer resistance to itraconazole, voriconazole and posaconazole. in the netherlands a dominant resistance mechanism referred to as tr/l98h is found. in a. fumigatus isolates recovered from clinical samples in dutch hospitals the prevalence of azole resistance varied between 0.8% and 9.4%. the tr/l98h resistance mechanism probably develops in our environment, as azoles are frequently used for crop protection and material preservation. i ...201222748367
frequency of fungi in respiratory samples from turkish cystic fibrosis patients.an increased isolation of fungi from the respiratory tract of patients with cystic fibrosis (cf) has been reported. the prevalence of different fungi in cf patients from turkey is not known. our aim was to determine the frequency of fungi in the respiratory tract of turkish cf patients. we investigated a total of 184 samples from 48 patients. samples were inoculated on medium b+ and chromagar candida. candida albicans was the predominant yeast isolated [30 patients (62.5%)], followed by c. parap ...201322747891
identification of fungi associated with rotylenchulus reniformis.the objective of this work was to isolate and identify fungi associated with r. reniformis in cotton roots. soil samples were collected in cotton fields naturally infested with r. reniformis and from cotton stock plants cultured in the greenhouse. nematodes extracted from the soil were observed under the stereoscope, and discolored eggs and vermiform stages colonized with mycelia were cultured on 1.5% water agar supplemented with antibiotics, and incubated at 27°c. identification of the nematoph ...201022736864
obstruction of a percutaneous pulmonary valve by an aspergillus mycotic thrombus mimicking massive pulmonary embolus.new technologies in the management of congenital and acquired heart disease may be associated with unfamiliar complications that may require repeated surgical intervention. a high index of suspicion for unusual problems and close collaboration between cardiologists and surgeons is essential when adopting evolving technologies. we report the case of near total obstruction of a 2.5-month-old implanted melody percutaneous pulmonary valve (ppv) with a thrombus mimicking saddle embolus causing right ...201222735023
μ-chain-deficient mice possess b-1 cells and produce igg and ige, but not iga, following systemic sensitization and inhalational challenge in a fungal asthma model.allergic bronchopulmonary aspergillosis is often difficult to treat and results in morbidity associated with chronic airway changes. this study assessed the requirement for b cells and their products in the allergic pulmonary phenotype in a murine model of fungal allergic asthma that mimics allergic bronchopulmonary aspergillosis. c57bl/6 and μmt mice (assumed to lack peripheral b cells) were sensitized with aspergillus fumigatus extract and challenged with two inhalation exposures of live conid ...201222732592
[role of neutrophil-derived reactive oxygen species in host defense and inflammation].neutrophil accumulation is a critical event in the pathogenesis of inflammation. the generation of hypochlorous acid by myeloperoxidase (mpo) in neutrophils is crucial to the host defense response. mpo-deficient (mpo-ko) mice showed severely reduced cytotoxicity to candida albicans, aspergillus fumigatus, cryptococcus neoformans and other microorganisms, demonstrating that an mpo-dependent oxidative system is important for in vivo host defense against fungi. on the other hand, impaired reactive ...201222728595
characteristics of nucleosomes and linker dna regions on the genome of the basidiomycete mixia osmundae revealed by mono- and dinucleosome mapping.we present findings on the nucleosomal arrangement in the genome of the basidiomycete mixia osmundae, focusing on nucleosomal linker dna regions. we have assembled the genomic sequences of m. osmundae, annotated genes and transcription start sites (tsss) on the genome, and created a detailed nucleosome map based on sequencing mono- and dinucleosomal dna fragments. the nucleosomal dna length distribution of m. osmundae is similar to that of the filamentous ascomycete aspergillus fumigatus, but di ...201222724063
non occupational chronic hypersensitivity pneumonitis due to aspergillus fumigatus on leaky walls. 201222722814
the transcriptional response to the inactivation of the pampk1 and pampk2 map kinase pathways in podospora anserina.transcription pattern during mycelium growth of podospora anserina was assayed by microarray analysis in wild type and in mutants affected in the map kinase genes pampk1 and pampk2 and in the nadph oxidase gene panox1. 15% of the genes have their expression modified by a factor two or more as growth proceeds in wild type. the genes whose expression is modified during growth in p. anserina are either not conserved or differently regulated in neurospora crassa and aspergillus niger, two fungi for ...201222721649
antimicrobial activities of aerva javanica and paeonia emodi plants.aerva javanica and paeonia emodi plants extracts were studied for antibacterial activity against escherichia coli (nctc 10418), klebsiella pneumoniae (atcc 700603), pseudomonas aeruginosa, staphylococcus aureus, salmonella typhi, staphylococcus epidermidis (nctc 11047) and methicillin resistant staphylococcus aureus (mrsa) (nctc 13143) and antifungal activity against aspergillus flavus, aspergillus fumigatus, aspergillus niger and fusarium solani. extracts were obtained by using methanol, n-hexa ...201222713942
azole preexposure affects the aspergillus fumigatus population in patients.the relationship between the azole preexposure of 86 patients and the genotype, azole susceptibility, and cyp51a polymorphisms of 110 corresponding aspergillus fumigatus isolates was explored. isolates carrying serial polymorphisms (f46y and m172v with or without n248t with or without d255e with or without e427k) had higher itraconazole mics (p = 0.04), although <2 μg/ml using the eucast methodology, were associated with two genetic clusters (p < 0.001) and with voriconazole preexposure of patie ...201222710122
immunity and tolerance to fungi in hematopoietic transplantation: principles and perspectives.resistance and tolerance are two complementary host defense mechanisms that increase fitness in response to low-virulence fungi. resistance is meant to reduce pathogen burden during infection through innate and adaptive immune mechanisms, whereas tolerance mitigates the substantial cost of resistance to host fitness through a multitude of anti-inflammatory mechanisms, including immunological tolerance. in experimental fungal infections, both defense mechanisms are activated through the delicate ...201222707953
antifungal therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.allergic bronchopulmonary aspergillosis (abpa) is an allergic reaction to colonisation of the lungs with the fungus aspergillus fumigatus and affects around 10% of people with cystic fibrosis. abpa is associated with an accelerated decline in lung function. high doses of corticosteroids are the main treatment for abpa; although the long-term benefits are not clear, their many side effects are well-documented. a group of compounds, the azoles, have activity against aspergillus fumigatus and have ...201222696329
adoptive immunity mediated by hla-a*0201 restricted asp f16 peptides-specific cd8+ t cells against aspergillus fumigatus infection.aspergillus fumigatus (a. fumigatus) is the most common pathogen of invasive aspergillosis (ia), a life-threatening infection in immunocompromised patients. recent findings revealed that cd8+ t cells can mediate cytotoxic activity against a. fumigatus. here, we bioinformatically identified three hla-a*0201-restricted peptides from asp f16, an a. fumigatus antigen which was previously shown to be involved in t cell immunity. our immunological results demonstrated that these peptides can potently ...201222696051
amino acid-derived 1,2-benzisothiazolinone derivatives as novel small-molecule antifungal inhibitors: identification of potential genetic targets.we have identified four synthetic compounds (dfd-vi-15, bd-i-186, dfd-v-49, and dfd-v-66) from an amino acid-derived 1,2-benzisothiazolinone (bzt) scaffold that have reasonable mic(50) values against a panel of fungal pathogens. these compounds have no structural similarity to existing antifungal drugs. three of the four compounds have fungicidal activity against candida spp., cryptococcus neoformans, and several dermatophytes, while one is fungicidal to aspergillus fumigatus. the kill rates of ...201222687516
experimental central nervous system aspergillosis therapy: efficacy, drug levels and localization, immunohistopathology, and toxicity.we have shown previously that high-dose lipid amphotericin preparations are not more efficacious than lower doses in aspergillosis. we studied toxicity, drug concentrations and localization, and quantitative infection concurrently, using a 4-day model of central nervous system (cns) aspergillosis to assess early events. mice given aspergillus fumigatus conidia intracerebrally, under a cyclophosphamide immunosuppressive regimen, were treated for 3 days (ambisome at 3 or 10 mg/kg of body weight, a ...201222687510
purification, crystallization and preliminary x-ray diffraction data of udp-galactopyranose mutase from aspergillus fumigatus.aspergillus fumigatus udp-galactopyranose mutase (afugm) is a potential drug target involved in the synthesis of the cell wall of this fungal pathogen. afugm was recombinantly produced in escherichia coli, purified and crystallized by the sitting-drop method, producing orthorhombic crystals that diffracted to a resolution of 3.25 å. the crystals contained four molecules per asymmetric unit and belonged to space group p2(1)2(1)2(1), with unit-cell parameters a = 127.72, b = 134.30, c = 173.84 å. ...201222684076
synthesis and evaluation of antimicrobial activity of 4h-pyrimido[2,1-b]benzothiazole, pyrazole and benzylidene derivatives of curcumin.a novel, one-pot, simple, efficient procedure for 4h-pyrimido[2,1-b]benzothiazole (4a-h), pyrazole (6a-d) and benzylidene (7a-d) derivatives of curcumin under solvent and solvent free conditions in microwave with good yield is have been synthesized. the synthesized compounds were evaluated for their antibacterial activity against gram-positive and gram-negative bacteria viz. staphylococcus aureus, pseudomonas aeruginosa, salmonella typhi, escherichia coli, bacillus cereus and providencia rettger ...201222683240
hog-mapk signaling regulates the adaptive responses of aspergillus fumigatus to thermal stress and other related stress.aspergillus fumigatus is naturally exposed to a highly variable environment and subjected to various kinds of stresses. high-osmolarity glycerol mitogen-activated protein kinase (hog-mapk) pathway plays a crucial role in regulating cellular homeostasis in response to environmental changes. here, we explored the contribution of hog-mapk pathway to the adaptive responses to thermal stress and other related stresses in a. fumigatus. we observed the phenotype features of wild-type strains and their ...201222678624
the two-component sensor kinase tcsc and its role in stress resistance of the human-pathogenic mold aspergillus fumigatus.two-component signaling systems are widespread in bacteria, but also found in fungi. in this study, we have characterized tcsc, the only group iii two-component sensor kinase of aspergillus fumigatus. tcsc is required for growth under hyperosmotic stress, but dispensable for normal growth, sporulation and conidial viability. a characteristic feature of the δtcsc mutant is its resistance to certain fungicides, like fludioxonil. both hyperosmotic stress and treatment with fludioxonil result in a t ...201222675534
molecular epidemiology of aspergillus fumigatus isolates harboring the tr34/l98h azole resistance mechanism.a rapid emergence of azole resistance has been observed in aspergillus fumigatus in the netherlands over the past decade. the dominant resistance mechanism appears to be of environmental origin and involves the tr(34)/l98h mutations in cyp51a. this resistance mechanism is now also increasingly being found in other countries. therefore, genetic markers were used to gain more insights into the origin and spread of this genotype. studies of 142 european isolates revealed that those with the tr(34)/ ...201222675126
restriction analysis of an amplified roda gene fragment to distinguish aspergillus fumigatus var. ellipticus from aspergillus fumigatus var. fumigatus.a previous multidisciplinary study indicated that gliotoxin-producing aspergillus fumigatus fresen. isolates from silage commodities mostly belonged to its variant a. fumigatus var. ellipticus raper & fennell. sequence analysis revealed the presence of a single nucleotide polymorphism at five positions in a fragment of the roda gene (coding for a hydrophobin rodleta protein) between aspergillus fumigatus var. fumigatus and aspergillus fumigatus var. ellipticus. a method was developed to distingu ...201222670589
molecular characterization of an adaptive response to alkylating agents in the opportunistic pathogen aspergillus fumigatus.an adaptive response to alkylating agents based upon the conformational change of a methylphosphotriester (mpt) dna repair protein to a transcriptional activator has been demonstrated in a number of bacterial species, but this mechanism appears largely absent from eukaryotes. here, we demonstrate that the human pathogen aspergillus fumigatus elicits an adaptive response to sub-lethal doses of the mono-functional alkylating agent n-methyl-n'-nitro-n-nitrosoguanidine (mnng). we have identified gen ...201222669901
development of monoclonal antibody-based galactomannoprotein antigen-capture elisas to detect aspergillus fumigatus infection in the invasive aspergillosis rabbit models.aspergillus fumigatus is one of the most prominent opportunistic fungal pathogens in immunocompromised hosts. early recognition of this infection along with prompt antifungal therapy may increase the survival rate. we expressed two potential bio-markers of a. fumigatus infection-galactomannoprotein afmp1p and afmp4p in pichia pastoris. we generated 33 monoclonal antibodies (mabs), 20 against recombinant afmp1p (rafmp1p) and the other 13 against recombinant afmp4p (rafmp4p). subsequently, we deve ...201222669560
a new type of hypersensitivity pneumonitis: salami brusher's disease.we observed five consecutive cases of hypersensitivity pneumonitis in subjects working in a salami factory. the workers had to clean the white mould growing on salami surface using a manual wire brush. the five patients (four female) had a mean age of 39 +/- 15 years; two were smokers. three patients had an acute clinical presentation with fever, dyspnoea, dry cough, oxygen desaturation, and presented at the emergency department with suspected diagnosis of community acquired pneumonia. the mean ...201222662646
functional characterization of an aspergillus fumigatus calcium transporter (pmca) that is essential for fungal infection.aspergillus fumigatus is a primary and opportunistic pathogen, as well as a major allergen, of mammals. the ca(+2)-calcineurin pathway affects virulence, morphogenesis and antifungal drug action in a. fumigatus. here, we investigated three components of the a. fumigatus ca(+2)-calcineurin pathway, pmca,-b, and -c, which encode calcium transporters. we demonstrated that crza can directly control the mrna accumulation of the pmca-c genes by binding to their promoter regions. crza-binding experimen ...201222649543
preliminary study on the antimicrobial activity of enicostemma littorale using different solvents.to study the antimicrobial activity of enicostemma littorale (e. littorale) using different solvents.201222647818
crystal structures of trypanosoma cruzi udp-galactopyranose mutase implicate flexibility of the histidine loop in enzyme activation.chagas disease is a neglected tropical disease caused by the protozoan parasite trypanosoma cruzi. here we report crystal structures of the galactofuranose biosynthetic enzyme udp-galactopyranose mutase (ugm) from t. cruzi, which are the first structures of this enzyme from a protozoan parasite. ugm is an attractive target for drug design because galactofuranose is absent in humans but is an essential component of key glycoproteins and glycolipids in trypanosomatids. analysis of the enzyme-udp n ...201222646091
aspergillus endocarditis in a native valve without prior cardiac surgery.aspergillus native valve endocarditis continues to be a lethal disease, even when maximal therapeutic options are taken. we describe herein a patient with mitral valve endocarditis due to aspergillus fumigatus following colon cancer and invasive pulmonary aspergillosis. voriconazole was effective in controlling pulmonary and cerebral aspergillosis, despite the relative ineffectiveness for the vegetation. with the combination of aggressive medical and surgical therapy, the patient survived and re ...201222644820
prenylation of a nonaromatic carbon of indolylbutenone by a fungal indole prenyltransferase.ftmpt1 from aspergillus fumigatus is a fungal indole prenyltransferase (pt) that normally catalyzes the regiospecific prenylation of brevianamide f (cyclo-l-trp-l-pro) at the c-2 position of the indole ring with dimethylallyl diphosphate (dmapp). interestingly, ftmpt1 exhibited remarkable substrate tolerance and accepted (e)-4-(1h-indol-3-yl)but-3-en-2-one (1) as a substrate to produce an unnatural novel α-prenylindolylbutenone (1a). this is the first demonstration of the prenylation of a nonaro ...201222642693
plga nanoparticles and nanosuspensions with amphotericin b: potent in vitro and in vivo alternatives to fungizone and ambisome.this paper describes the development of poly(d,l-lactide-co-glycolide) (plga) nanoparticles (nps) and nanosuspensions with the polyene antibiotic amphotericin b (amb). the nanoformulations were prepared using nanoprecipitation and were characterised with respect to size, zeta potential, morphology, drug crystallinity and content. standard in vitro sensitivity tests were performed on mrc-5 cells, red blood cells, leishmania infantum promastigotes and intracellular amastigotes and the fungal speci ...201222641062
allergic bronchopulmonary aspergillosis.allergic bronchopulmonary aspergillosis (abpa) is caused by an exaggerated t(h)2 response to the ubiquitous mold aspergillus fumigatus. abpa develops in a small fraction of patients with cystic fibrosis and asthma, suggesting that intrinsic host defects play a major role in disease susceptibility. this article reviews current understanding of the immunopathology, clinical and laboratory findings, and diagnosis and management of abpa. it highlights clinical and laboratory clues to differentiate a ...201222640845
pharmacodynamics of voriconazole in a dynamic in vitro model of invasive pulmonary aspergillosis: implications for in vitro susceptibility breakpoints.voriconazole is a first-line agent for the treatment of invasive pulmonary aspergillosis (ipa). there are increasing reports of aspergillus fumigatus isolates with reduced susceptibility to voriconazole.201222634880
aspergillus fumigatus calcineurin interacts with a nucleoside diphosphate kinase.the ca(2+)-calcineurin pathway affects virulence and morphogenesis in filamentous fungi. here, we identified 37 cala-interacting proteins that interact with the catalytic subunit of calcineurin (cala) in aspergillus fumigatus, including the nucleoside diphosphate kinase (swoh). the in vivo interaction between cala and swoh was validated by bimolecular fluorescence complementation. a. fumigatus swoh is an essential gene. therefore, a temperature-sensitive conditional mutant strain with a point mu ...201222634424
synthesis of s-triazine-based thiazolidinones as antimicrobial agents.a novel series of thiazolidinone derivatives, namely 4-{4-dimethylamino-6-[4-oxo-2-phenyl-5-(4-pyridin-2-yl-piperazin-1-ylmethyl)-thiazolidin-3-yl]-[1,3,5]-triazin-2-yloxy}-1-methyl-1h-quinolin-2-ones, have been synthesized from the key intermediate 4-(4-amino-6-dimethylamino-[1,3,5]-triazin-2-yloxy)-1-methyl-1h-quinolin-2-one (5). compound 5 was condensed with various aldehydes to give schiff base derivatives, which after cyclization gave thiazolidinones that were linked with 1-pyridin-2-yl-pip ...201222624326
salvage therapy with topical antifungal for aspergillus fumigatus empyema complicating extrapleural pneumonectomy.we describe an unusual case of aspergillus fumigatus empyema and bronchopleural fistulae after extrapleural pneumonectomy (epp) and chemoradiotherapy (crt), which was treated successfully under salvage conditions with debridement, an innovative topical antifungal application and supplemented systemic antifungal therapy and which went on for a definitive surgical procedure. combinations of crt and epp have been recommended in a select group of patients with malignant mesothelioma. irrespective of ...201222617507
pharmacodynamics of itraconazole against aspergillus fumigatus in an in vitro model of the human alveolus: perspectives on the treatment of triazole-resistant infection and utility of airway administration.itraconazole is used for the prevention and treatment of infections caused by aspergillus fumigatus. an understanding of the pharmacodynamics of itraconazole against wild-type and triazole-resistant strains provides a basis for innovative therapeutic strategies for treatment of infections. an in vitro model of the human alveolus was used to define the pharmacodynamics of itraconazole. galactomannan was used as a biomarker. the effect of systemic and airway administration of itraconazole was asse ...201222615280
pseudomembranous necrotizing tracheobronchial aspergillosis: an analysis of 16 cases.in our clinical practice we have been attracted by a group of patients with airway aspergillosis who have airway obstruction; we termed the condition as pseudomembranous necrotizing tracheobronchial aspergillosis (pnta). in this study we analyzed the clinical data from patients with pnta, so as to guide the diagnosis and treatment of the disease.201222613594
studies on an alkali-thermostable xylanase from aspergillus fumigatus ma28.an alkalitolerant fungus, aspergillus fumigatus strain ma28 produced significant amounts of cellulase-free xylanase when grown on a variety of agro-wastes. wheat bran as the sole carbon source supported higher xylanase production (8,450 u/l) than xylan (7,500 u/l). soybean meal was observed to be the best nitrogen source for xylanase production (9,000 u/l). optimum medium ph for xylanase production was 8 (9,800 u/l), though, significant quantities of the enzyme was also produced at ph 7 (8,500 u ...201122611527
orbital aspergillosis: voriconazole - the new standard treatment?to describe a case of invasive orbital aspergillosis and evaluate treatments and outcomes.201222611368
incidence of dsrna mycoviruses in a collection of aspergillus fumigatus isolates.a collection of clinical and environmental isolates of the opportunistic human pathogen, aspergillus fumigatus, were screened for the presence of mycoviruses and 6.6 % of 366 isolates contained dsrna segments ranging in size from ~1.0 to 4.0 kbp. the dsrnas were categorised into three different groups comprising bipartite dsrnas, quadripartite dsrnas, representative isolates of which have both been sequenced, and an uncharacterised mycovirus, whose genome apparently consists of four dsrnas 1-2.5 ...201222610906
blood basophils from cystic fibrosis patients with allergic bronchopulmonary aspergillosis are primed and hyper-responsive to stimulation by aspergillus allergens.fifteen to sixty percent of cystic fibrosis patients harbor aspergillus fumigatus (af) in their airways (cf-ac) and some will develop allergic bronchopulmonary aspergillosis (cf-abpa). since basophils play a key role in allergy, we hypothesized that they would display alterations in cf-abpa patients compared to cf-ac or patients without af colonization (cf).201222608296
in vitro efficacy of the combination of voriconazole and anidulafungin against voriconazole-resistant cyp51a mutants of aspergillus fumigatus.we selected voriconazole-resistant (vcz-r) aspergillus fumigatus in the laboratory, characterized the cyp51a gene for possible mutations and evaluated the in vitro activities of voriconazole and anidulafungin alone and in combination against vcz-r isolates of a. fumigatus using a fractional inhibitory concentration index (fici) methodology. voriconazole-resistant isolates were selected from wild-type a. fumigatus isolates in the laboratory by a 2-step selection process (plus 1 clinical isolate). ...201222608136
prenatal exposure to allergen, dna methylation, and allergy in grandoffspring mice.prenatal allergen exposure has been linked to both induction and protection of allergic sensitization in offspring. we hypothesized that prenatal exposure of mice (f0) to aspergillus fumigatus (a. fumigatus) would be associated with decreased immunoglobulin (ig) e and airway eosinophilia and alterations in cpg methylation of t-helper genes in third-generation mice (f2).201222583153
high prevalence of triazole resistance in aspergillus fumigatus, especially mediated by tr/l98h, in a french cohort of patients with cystic fibrosis.triazole resistance in aspergillus fumigatus due to a single azole resistance mechanism (tr/l98h) is increasingly reported in european countries. data from patients with cystic fibrosis (cf) are limited. our study aimed to investigate the prevalence and molecular mechanisms of azole resistance in a. fumigatus in a cohort of patients with cf.201222581906
pentraxin 3(ptx 3): an endogenous modulator of the inflammatory response.inflammatory or anti-inflammatory? that is the question as far as the acute-phase response and its mediators, the pentraxins, are concerned. only some ten years ago, the classical or short pentraxin c-reactive protein and the newly discovered long pentraxin ptx3 were considered to exert most of the detrimental effects of acute inflammation, whether microbial or sterile in origin. however, accumulating evidence suggests an at least dichotomous, context-dependent outcome attributable to the pentra ...201222577258
new metabolites from the marine-derived fungus aspergillus fumigatus.a new alkaloid, fumiquinazoline k (1), and a new nordammarane triterpenoid (2), together with three known diketopiperazines (3-5) and tryptoquivaline f (6) have been isolated from a marine strain of aspergillus fumigatus kmm 4 631 associated with the soft coral sinularia sp. their structures were determined by hr-ms and 1d and 2d nmr. compounds 3-5 exhibit weak cytotoxicity against cytoplasm non-specific esterase in ehrlich carcinoma cells. compound 3 also induces early apoptosis of the same cel ...201222574452
identification and characterization of antifungal compounds using a saccharomyces cerevisiae reporter bioassay.new antifungal drugs are urgently needed due to the currently limited selection, the emergence of drug resistance, and the toxicity of several commonly used drugs. to identify drug leads, we screened small molecules using a saccharomyces cerevisiae reporter bioassay in which s. cerevisiae heterologously expresses hik1, a group iii hybrid histidine kinase (hhk) from magnaporthe grisea. group iii hhks are integral in fungal cell physiology, and highly conserved throughout this kingdom; they are ab ...201222574132
resistance to voriconazole due to a g448s substitution in aspergillus fumigatus in a patient with cerebral aspergillosis.a voriconazole-resistant isolate of aspergillus fumigatus was recovered from an immunocompetent patient receiving long-term antifungal therapy for cerebral aspergillosis. a g448s amino acid substitution in the azole target (cyp51a) was identified as the cause of the resistance phenotype. this article describes the first isolation of a voriconazole-resistant a. fumigatus isolate from an immunocompetent patient in spain.201222573589
occlusive fungal tracheitis in 4 captive bottlenose dolphins (tursiops truncatus).respiratory disease is common in dolphins, primarily affecting pulmonary parenchyma and sparing large airways. over a 10-year period, 4 captive adult bottlenose dolphins succumbed to chronic, progressive respiratory disease with atypical recurrent upper respiratory signs. all dolphins had severe, segmental to circumferential fibrosing tracheitis that decreased luminal diameter. histologically, tracheal cartilage, submucosa, and mucosa were distorted and replaced by extensive fibrosis and pyogran ...201322573576
mucoadhesive nanoparticles for prolonged ocular delivery of natamycin: in vitro and pharmacokinetics studies.the aim of this study was to prepare natamycin encapsulated lecithin/chitosan mucoadhesive nanoparticles (nps) for prolonged ocular application. these nps were characterized by their mean particle size 213nm, encapsulation efficiency 73.57%, with a theoretical drug loading 5.09% and zeta potential +43. in vitro release exhibited a biphasic drug release profile with initial burst followed by a very slow drug release. the mic(90) and zone of inhibition of nps showed similar antifungal activity as ...201222569234
treatment of aspergillus fumigatus in patients with cystic fibrosis: a randomized, placebo-controlled pilot study.many patients with cystic fibrosis develop persistent airway infection/colonization with aspergillus fumigatus, however the impact of a. fumigatus on clinical outcomes remains unclear. the objective of this study was to determine whether treatment directed against aspergillus fumigatus improves pulmonary function and clinical outcomes in patients with cystic fibrosis (cf).201222563440
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