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Mevalonate governs interdependency of ergosterol and siderophore biosyntheses in the fungal pathogen Aspergillus fumigatus.Aspergillus fumigatus is the most common airborne fungal pathogen for humans. In this mold, iron starvation induces production of the siderophore triacetylfusarinine C (TAFC). Here we demonstrate a link between TAFC and ergosterol biosynthetic pathways, which are both critical for virulence and treatment of fungal infections. Consistent with mevalonate being a limiting prerequisite for TAFC biosynthesis, we observed increased expression of 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase (Hmg1) u ...201122106303
mutually facilitated dispersal between the nonmotile fungus aspergillus fumigatus and the swarming bacterium paenibacillus vortex.in the heterogeneous environment surrounding plant roots (the rhizosphere), microorganisms both compete and cooperate. here, we show that two very different inhabitants of the rhizosphere, the nonmotile fungus aspergillus fumigatus and the swarming bacterium paenibacillus vortex, can facilitate each other's dispersal. a. fumigatus conidia (nonmotile asexual fungal spores) can be transported by p. vortex swarms over distances of at least 30 cm and at rates of up to 10.8 mm h(-1). moreover, conidi ...201122106274
Synthesis and Antimicrobial Evaluation of New Pyrano[4,3-b]pyran and Pyrano[3,2-c]chromene Derivatives Bearing a 2-Thiophenoxyquinoline Nucleus.A new series of pyrano[4,3-b]pyran 4a-i and pyrano[3,2-c]chromene 6a-r derivatives bearing a 2-thiophenoxyquinoline nucleus were synthesized by reaction of 2-(4-(un)-substituted thiophenoxy)quinoline-3-carbaldehydes 2a-i with 6-methyl-4-hydroxypyran-2-one 3 and 4-hydroxy-6-(un)-substituted-2H-chromen-2-one 5a-b respectively and malononitrile at room temperature in the presence of KOH as a basic catalyst. All the compounds were screened against three Gram-positive bacteria (Streptococcus pneumoni ...201122105795
association between indoor fungi in delhi homes and sensitization in children with respiratory allergy.indoor fungi are potential sensitizing agents in children and their detection and quantification in indoor air are important in the diagnosis and environmental management of fungal allergies. the objective of this investigation was to assess the prevalence of fungal allergies in children in delhi and to study the association between mold counts in the homes of children and their sensitization to respective fungal extracts. fungal concentrations and seasonality were studied at two-week intervals ...201122103346
Galactosaminogalactan, a new immunosuppressive polysaccharide of Aspergillus fumigatus.A new polysaccharide secreted by the human opportunistic fungal pathogen Aspergillus fumigatus has been characterized. Carbohydrate analysis using specific chemical degradations, mass spectrometry, ¹H and ¹³C nuclear magnetic resonance showed that this polysaccharide is a linear heterogeneous galactosaminogalactan composed of a1-4 linked galactose and a1-4 linked N-acetylgalactosamine residues where both monosacharides are randomly distributed and where the percentage of galactose per chain vari ...201122102815
Spinal aspergillosis in pheasants. 201122102357
innate recognition of cell wall β-glucans drives invariant natural killer t cell responses against fungi.inkt cells are innate t lymphocytes recognizing endogenous and foreign lipid antigens presented in the mhc-like molecule cd1d. the semi-invariant inkt cell tcr can detect certain bacterial and parasitic lipids and drive inkt cell responses. how inkt cells respond to fungi, however, is unknown. we found that cd1d-deficient mice, which lack inkt cells, poorly control infection with the fungal pathogen aspergillus fumigatus. furthermore, a. fumigatus rapidly activates inkt cells in vivo and in vitr ...201122100160
inkts foil fungi.fungal cell wall polysaccharides are potent inducers of immune responses. cohen et al. (2011) demonstrate that innate recognition of fungal β-(1,3) glucan triggers effector functions of invariant natural killer t (inkt) cells through indirect, cytokine-driven activation, a process that mediates optimal protection against the opportunistic mold aspergillus fumigatus.201122100157
Biosynthesis and function of gliotoxin in Aspergillus fumigatus.Gliotoxin (GT) is the prototype of the epidithiodioxopiperazine (ETP)-type fungal toxins. GT plays a critical role in the pathobiology of Aspergillus fumigatus. It modulates the immune response and induces apoptosis in different cell types. The toxicity has been attributed to the unusual intramolecular disulfide bridge, which is the functional motif of all ETPs. Because of the extraordinary structure and activity of GT, this fungal metabolite has been the subject of many investigations. The bios ...201122094977
a protective role for periostin and tgf-β in ige-mediated allergy and airway hyperresponsiveness.the pathophysiology of asthma involves allergic inflammation and remodelling in the airway and airway hyperresponsiveness (ahr) to cholinergic stimuli, but many details of the specific underlying cellular and molecular mechanisms remain unknown. periostin is a matricellular protein with roles in tissue repair following injury in both the skin and heart. it has recently been shown to be up-regulated in the airway epithelium of asthmatics and to increase active tgf-β. though one might expect perio ...201122093101
increased chitinase expression and fungal-specific antibodies in the bronchoalveolar lavage fluid of asthmatic children.background: increasing evidence highlights the contribution of chitinases and fungal infection to the development of asthma. objective: the purpose of this study was to characterize chitinase expression and serological markers of fungal infection in children with severe asthma. methods: bronchoalveolar lavage fluid (balf) was collected from children undergoing clinically indicated flexible bronchoscopy. a diagnosis of asthma was confirmed by pulmonary function testing. balf was tested for chitin ...201122092749
sexual development and cryptic sexuality in fungi: insights from aspergillus species.major insights into sexual development and cryptic sexuality within filamentous fungi have been gained from investigations using aspergillus species. here, an overview is first given into sexual morphogenesis in the aspergilli, describing the different types of sexual structures formed and how their production is influenced by a variety of environmental and nutritional factors. it is argued that the formation of cleistothecia and accessory tissues, such as hülle cells and sclerotia, should be vi ...201222091779
A pulmonary aspergillosis case with fatal course in a patient with SIRS clinic.A 77-year-old male patient with a history of tuberculosis applied to emergency service with complaints of confusion, shortness of breath, tachycardia, hypothermia and hypotension. A bronchoalveolar lavage culture was collected because a fungus ball was seen on repeat chest X-ray and thoracic CT of the patient. Aspergillus fumigatus grew and voricona-zole treatment was started, but the patient was lost from multiple organ failure (MOF). In diagnosis of patients with SIRS clinic, causative factor ...201122091235
A new antifungal coumarin from Clausena excavata.A new ?-lactone coumarin, named as excavarin-A, showing antifungal activity was isolated from the leaves of Clausena excavata by bioassay guided fractionation method. The structure was elucidated by spectroscopic data analysis and identified as 7((2E)-4(4,5-dihydro-3-methylene-2-oxo-5-furanyl)-3-methylbut-2-enyloxy) coumarin. Minimum inhibitory concentration (MIC) was determined against fifteen fungal strains pathogenic against plants and human. The least MIC was recorded against the human patho ...201222088496
maximum saccharification of cellulose complex by an enzyme cocktail supplemented with cellulase from newly isolated aspergillus fumigatus ecu0811.either the natural biodegradation process or the industrial hydrolytic process requires synergistic interactions between various cellulases. however, it is sometimes impeded by low hydrolytic rate of existing cellulases and the lack of accessory enzymes. herein, the ability of a commercial cellulase (spezyme cp, from genencor) to degrade steam explosion-pretreated corn stover was significantly improved. firstly, a fungal cellulase producer, aspergillus fumigatus ecu0811, was isolated from hundre ...201122086563
control of clinical pathogens by the haemolymph of paratelphusa hydrodromous, a freshwater crab.in the present study, effort has been made to find the antimicrobial activity of haemolymph collected from freshwater crab, paratelphusa hydrodromous. the haemolymph collected was tested for antimicrobial assay by disc diffusion method against clinical pathogens. five bacterial species, namely, escherichia coli, klebsiella pneumonia, proteus mirabilis, pseudomonas aeruginosa, staphylococcus aureus, and five fungal strains, namely and aspergillus flavus, aspergillus fumigatus, aspergillus niger, ...201122084719
Antioxidant Activity of Aspergillus fumigatus.The antioxidant activity of Aspergillus fumigatus was assayed by different procedures and correlated with its extracellular total phenolic contents. Different physio-chemical parameters were optimized to enhance the activity. The culture grown under stationary conditions for 10 days at 25°C at pH 7 gave the best antioxidant activity. Statistical approaches demonstrated sucrose and NaNO(3) to be the most suitable carbon and nitrogen sources, respectively. Response surface analysis showed 5% sucro ...201122084718
Disruption of the Phospholipase D Gene Attenuates the Virulence of Aspergillus fumigatus.Aspergillus fumigatus is the most prevalent airborne fungal pathogen that induces serious infections in immunocompromised patients. Phospholipases are key enzymes in pathogenic fungi that cleave host phospholipids, resulting in membrane destabilization and host cell penetration. However, knowledge of the impact of phospholipases on A. fumigatus virulence is rather limited. In this study, disruption of the pld gene encoding phospholipase D (PLD), an important member of the phospholipase protein f ...201222083709
Induction of Group IVC Phospholipase A2 in Allergic Asthma: Transcriptional Regulation by TNF-a in Bronchoepithelial Cells.Airway inflammation in allergen-induced asthma is associated with eicosanoid release. These bioactive lipids exhibit anti- and pro-inflammatory activities with relevance to pulmonary pathophysiology. We hypothesized that sensitization/challenge using an extract from the ubiquitous fungus, Aspergillus fumigatus (Af), in a mouse model of allergic asthma would result in altered phospholipase gene expression, thus modulating the downstream eicosanoid pathway. We observed the most significant inducti ...201122082005
CADRE: the Central Aspergillus Data REpository 2012.The Central Aspergillus Data REpository (CADRE; http://www.cadre-genomes.org.uk) is a public resource for genomic data extracted from species of Aspergillus. It provides an array of online tools for searching and visualising features of this significant fungal genus. CADRE arose from a need within the medical community to understand the human pathogen Aspergillus fumigatus. Due to the paucity of Aspergillus genomic resources 10 years ago, the long-term goal of this project was to collate and mai ...201222080563
The Aspergillus Genome Database (AspGD): recent developments in comprehensive multispecies curation, comparative genomics and community resources.The Aspergillus Genome Database (AspGD; http://www.aspgd.org) is a freely available, web-based resource for researchers studying fungi of the genus Aspergillus, which includes organisms of clinical, agricultural and industrial importance. AspGD curators have now completed comprehensive review of the entire published literature about Aspergillus nidulans and Aspergillus fumigatus, and this annotation is provided with streamlined, ortholog-based navigation of the multispecies information. AspGD fa ...201222080559
iliopsoas abscess caused by aspergillus fumigatus complicated by pulmonary aspergillosis.we report a case of iliopsoas abscess caused by aspergillus fumigatus with pulmonary complications. a 60-year-old man was admitted to the showa university hospital department of gastroenterology with fulminant hepatitis b on april 14, 2010, and treated with steroids. although fulminant hepatitis b was improved by steroid and symptomatic therapy, he developed a fever on hospital day 39. the chest x-ray film showed a nodular lesion in the right middle-lower lung field, and both the (1 → 3)-β-d: -g ...201122080203
Invasive mold infections in chronic granulomatous disease: a 25-year retrospective survey.Invasive fungal infection (IFI) represents a life-threatening condition for patients with chronic granulomatous disease (CGD) and causes one-third of deaths in this population. This study offers a descriptive review of invasive mold infection (mIFI) in children with CGD over an extended period of time.201122080130
[general epidemiology of invasive fungal disease.]invasive mycoses associated with high morbidity and mortality rates are increasing among immunocompromised or severely ill patients. candida, cryptococcus, pneumocystis and aspergillus are most prevalent agents with varying distribution as regards geography, patient condition and hospital units. the latest multicentre candidaemia survey conducted in spain, showed c. albicans as the most frequently isolated species followed by c. parapsilosis, c. glabrata, c. tropicalis and c. krusei in contrast ...201122079232
pseudomonas aeruginosa inhibits the growth of cryptococcus species.pseudomonas aeruginosa is a ubiquitous and opportunistic bacterium that inhibits the growth of different microorganisms, including gram-positive bacteria and fungi such as candida spp. and aspergillus fumigatus. in this study, we investigated the interaction between p. aeruginosa and cryptococcus spp. we found that p. aeruginosa pa14 and, to a lesser extent, pao1 significantly inhibited the growth of cryptococcus spp. the inhibition of growth was observed on solid medium by the visualization of ...201122076410
aspergillus fumigatus densities in relation to forest succession and edge effects: implications for wildlife health in modified environments.the hihi (or stitchbird, notiomystis cincta) is a new zealand endemic nectivorous forest bird now restricted to one pristine island. relocation to establish viable hihi populations on other islands has been the main conservation action since the early 1980s. to date, hihi reintroductions to young growth islands have had poor success despite the absence of mammalian predators. it was thought that past failures were due to food limitation, but research suggests that food limitation alone cannot ac ...201122076057
Molecular assay to detect nosocomial fungal infections in intensive care units.The aims of this study were to determine the incidence of fungal infections in hospital intensive care units and to evaluate a molecular method to detect these infections.201122075290
in silico characterization of alkaline proteases from different species of aspergillus.a total of 49 protein sequences of alkaline proteases retrieved from genbank representing different species of aspergillus have been characterized for various physiochemical properties, homology search, multiple sequence alignment, motif, and super family search and phylogenetic tree construction. the sequence level homology was obtained among different groups of alkaline protease enzymes, viz alkaline serine protease, oryzin, calpain-like protease, serine protease, subtilisin-like alkaline prot ...201122072140
localization and activity of the calcineurin catalytic and regulatory subunit complex at the septum is essential for hyphal elongation and proper septation in aspergillus fumigatus.calcineurin, a heterodimer composed of the catalytic (cnaa) and regulatory (cnab) subunits, plays key roles in growth, virulence and stress responses of fungi. to investigate the contribution of cnaa and cnab to hyphal growth and septation, δcnab and δcnaaδcnab strains of aspergillus fumigatus were constructed. cnaa colocalizes to the contractile actin ring early during septation and remains at the centre of the mature septum. while cnab's septal localization is cnaa-dependent, cnaa's septal loc ...201122066998
repeated exposure to aspergillus fumigatus conidia results in cd4+ t cell-dependent and -independent pulmonary arterial remodeling in a mixed th1/th2/th17 microenvironment that requires interleukin-4 (il-4) and il-10.pulmonary arterial remodeling is a pathological process seen in a number of clinical disease states, driven by inflammatory cells and mediators in the remodeled artery microenvironment. in murine models, th2 cell-mediated immune responses to inhaled antigens, such as purified aspergillus allergen, have been reported to induce remodeling of pulmonary arteries. we have previously shown that repeated intranasal exposure of healthy c57bl/6 mice to viable, resting aspergillus fumigatus conidia leads ...201222064716
pharmacodynamic effects of simulated standard doses of antifungal drugs against aspergillus species in a new in vitro pharmacokinetic/pharmacodynamic model.in conventional μιc tests, fungi are exposed to constant drug concentrations, whereas in vivo, fungi are exposed to changing drug concentrations. therefore, we developed a new in vitro pharmacokinetic/pharmacodynamic model where human plasma pharmacokinetics of standard doses of 1 mg/kg amphotericin b, 4 mg/kg voriconazole, and 1 mg/kg caspofungin were simulated and their pharmacodynamic characteristics were determined against three clinical isolates of aspergillus fumigatus, aspergillus flavus, ...201222064546
α1,3 glucans are dispensable in aspergillus fumigatus.a triple α1,3 glucan synthase mutant of aspergillus fumigatus obtained by successive deletions of the three α1,3 glucan synthase genes (ags1, ags2, and ags3) has a cell wall devoid of α1,3 glucans. the lack of α1,3 glucans affects neither conidial germination nor mycelial vegetative growth and is compensated by an increase in β1,3 glucan and/or chitin content.201222058140
berberine and itraconazole are not synergistic in vitro against aspergillus fumigatus isolated from clinical patients.the incidence of aspergillus fumigatus infections has become more frequent as a consequence of widespread immunosuppression. at present, the number of available antifungal agents in the clinic is limited, and most of them, such as itraconazole (icz), are toxic and show resistance. berberine (ber) is a plant alkaloid used in the clinic mainly for alimentary infections. we have used ber and icz to measure in vitro resistance in a. fumigatus isolated from clinical patients. the minimum inhibitory c ...201122051933
Antifungal treatment affects the laboratory diagnosis of invasive aspergillosis.Aims The purpose of this study was to investigate the performance of non-invasive diagnostic tests such as galactomannan enzyme immunoassay and quantitative PCR in the early diagnosis of invasive aspergillosis (IA), and how these tests are impacted upon by the use of different classes of antifungal agents in an in-vivo model of IA. Methods A standardised rat inhalation model of IA was used to examine the effects of an azole, posaconazole, a polyene, amphotericin B and an echinocandin caspofungi ...201222049217
pyomelanin formation in aspergillus fumigatus requires hmgx and the transcriptional activator hmgr but is dispensable for virulence.the opportunistic human pathogenic fungus aspergillus fumigatus is able to produce the dark brown pigment pyomelanin by degradation of l-tyrosine. pyomelanin was shown to protect the fungus against reactive oxygen intermediates as well as cell wall disturbing compounds and is therefore assumed to protect against immune effector cells during the infection process. several genes for tyrosine degradation and pyomelanin formation are organized in a cluster in the genome of a. fumigatus. here, we aim ...201122046314
development of non-natural flavanones as antimicrobial agents.with growing concerns over multidrug resistance microorganisms, particularly strains of bacteria and fungi, evolving to become resistant to the antimicrobial agents used against them, the identification of new molecular targets becomes paramount for novel treatment options. recently, the use of new treatments containing multiple active ingredients has been shown to increase the effectiveness of existing molecules for some infections, often with these added compounds enabling the transport of a t ...201122039419
Dectin-1-Dependent Interleukin-22 Contributes to Early Innate Lung Defense against Aspergillus fumigatus.We have previously reported that mice deficient in the beta-glucan receptor Dectin-1 displayed increased susceptibility to Aspergillus fumigatus lung infection in the presence of lower interleukin 23 (IL-23) and IL-17A production in the lungs and have reported a role for IL-17A in lung defense. As IL-23 is also thought to control the production of IL-22, we examined the role of Dectin-1 in IL-22 production, as well as the role of IL-22 in innate host defense against A. fumigatus. Here, we show t ...201222038916
microwave-mediated enzyme-linked immunosorbent assay procedure.here we demonstrate a novel microwave-mediated enzyme-linked immunosorbent assay (melisa) method that has dramatically reduced the enzyme-linked immunosorbent assay (elisa) timing to less than 5min with a result comparable to that obtained by 18-h conventional elisa. efficacy of the melisa procedure is demonstrated by detecting human immunoglobulin g (igg), rabbit igg, human immunoglobulin e (ige), human interleuken 1β (il-1β), entamoeba histolytica antibody, and aspergillus fumigatus antibody. ...201122033289
haca-independent functions of the er stress sensor irea synergize with the canonical upr to influence virulence traits in aspergillus fumigatus.endoplasmic reticulum (er) stress is a condition in which the protein folding capacity of the er becomes overwhelmed by an increased demand for secretion or by exposure to compounds that disrupt er homeostasis. in yeast and other fungi, the accumulation of unfolded proteins is detected by the er-transmembrane sensor irea/ire1, which responds by cleaving an intron from the downstream cytoplasmic mrna haca/hac1, allowing for the translation of a transcription factor that coordinates a series of ad ...201122028661
isolation of multiple-triazole-resistant aspergillus fumigatus strains carrying the tr/l98h mutations in the cyp51a gene in india.azole resistance in aspergillus fumigatus isolates impacts on the management of aspergillosis since azoles are primary agents used for prophylaxis and therapy. we report the emergence of resistance to triazoles in two a. fumigatus isolates from patients in delhi, india.201122028200
antifungal susceptibilities of aspergillus fumigatus clinical isolates obtained in nagasaki, japan.we investigated the triazole, amphotericin b, and micafungin susceptibilities of 196 a. fumigatus clinical isolates in nagasaki, japan. the percentages of non-wild-type (non-wt) isolates for which mics of itraconazole, posaconazole, and voriconazole were above the ecv were 7.1%, 2.6%, and 4.1%, respectively. a g54 mutation in cyp51a was detected in 64.2% (9/14 isolates) and 100% (5/5 isolates) of non-wt isolates for itraconazole and posaconazole, respectively. amphotericin b mics of ≥2 μg/ml and ...201222024829
oligopeptide transport and regulation of extracellular proteolysis are required for growth of aspergillus fumigatus on complex substrates but not for virulence.moulds are characterized by their saprophytic lifestyle that is based on osmotrophy. among them, aspergillus fumigatus has emerged as the leading cause of fungal infections in the presence of an underlying immunodeficiency. to assess the role of its nutritional versatility for virulence, transcriptional profiling studies in the presence of varying sources of nitrogen were carried out and revealed an extensive reprogramming of the fungal transcriptome when shifting to a proteinaceous growth subst ...201122023286
isolation and identification of microbes associated with mobile phones in dammam in eastern saudi arabia.this study was conducted to determine microbial contamination of mobile phones in the city of dammam, in the eastern region of saudi arabia, and identify the most important microbial species associated with these phones in order to take the necessary remedial measures.201022022665
spinal aspergillosis in pheasants. 201122021268
analysis of fungal contamination and disinfection of toothbrushes.the aim of this study is to determine the fungal species in the toothbrushes of residents of a neighborhood on the east side of teresina - pi, and to assess the efficiency of a disinfection method based on 2% sodium hypochlorite. fifty toothbrushes were divided into two groups: group a comprised 30 toothbrushes used by the residents and group b (control group) 20 new toothbrushes. fungal evaluation was conducted in sabouraud culture medium containing chloramphenicol and chromagar candida. later ...201122010412
[Synthesis and antimicrobial evaluation of coumarin-based benzotriazoles and their synergistic effects with chloromycin and fluconazole].A series of new coumarin-based benzotriazole derivatives were successfully synthesized via a multi-step sequence of cyclization, etherification and N-alkylation, and were confirmed by 1H NMR, IR, MS spectra as well as elemental analyses. All these synthesized coumarin compounds were evaluated for in vitro antimicrobial activities against four Gram-positive bacteria, four Gram-negative bacteria and three fungi by two fold serial dilution technique. The bioactive assay showed that all these prepar ...201122010349
Antifungal effect of the essential oil of Thymus broussonetii Boiss endogenous species of Morocco.The aim of the study was to determine the antifungal effects of the essential oil of Thymus broussonetii Boiss (EOT), an endemic plant in Morocco against Candida albicans, Aspergillus fumigatus and the dermatophytes. EOT was extracted by steam distillation. A suspension of up to 500?µL of C. albicans at a concentration of 10(8)?CFU?mL(-1) and A. fumigatus at a concentration of 10(10)?spores?mL(-1) were inhibited by 20?µL of EOT incorporated in tubes containing 4?mL of Sabouraud broth. In Saboura ...201122007627
srebp-dependent triazole susceptibility in aspergillus fumigatus is mediated through direct transcriptional regulation of erg11a (cyp51a).as triazole antifungal drug resistance during invasive aspergillus fumigatus infection has become more prevalent, the need to understand mechanisms of resistance in a. fumigatus has increased. the presence of two erg11 (cyp51) genes in aspergillus spp. is hypothesized to account for the inherent resistance of this mold to the triazole fluconazole (flc). recently, an a. fumigatus null mutant of a transcriptional regulator in the sterol regulatory element binding protein (srebp) family, the δsrba ...201222006005
Ultrashort Peptide bioconjugates are exclusively antifungal agents and synergize with cyclodextrin and amphotericin B.Many natural broad-spectrum cationic antimicrobial peptides (AMPs) possess a general mode of action that is dependent on lipophilicity and charge. Modulating the lipophilicity of AMPs by the addition of a fatty acid has been an effective strategy to increase the lytic activity and can further broaden the spectrum of AMPs. However, lipophilic modifications that narrow the spectrum of activity and exclusively direct peptides to fungi are less common. Here, we show that short peptide sequences can ...201222006001
In Vitro Acquisition of Secondary Azole Resistance in Aspergillus fumigatus Isolates after Prolonged Exposure to Itraconazole: Presence of Heteroresistant Populations.Secondary resistance to azoles in Aspergillus fumigatus isolates from patients taking long-term itraconazole therapy has been described. We studied the acquisition of secondary azole resistance in 20 A. fumigatus isolates with no mutations at codon 54, 98, 138, 220, 432, or 448 in the cyp51A gene. Adjusted conidium inocula (3 × 10(7) CFU/ml) of each isolate were prepared and progressively or directly exposed to increasing itraconazole concentrations, ranging from 0.5 µg/ml to 16 µg/ml. Itraconaz ...201222006000
Rapid Induction of Multiple Resistance Mechanisms in Aspergillus fumigatus during Azole Therapy: a Case Study and Review of the Literature.Nine consecutive isogenic Aspergillus fumigatus isolates cultured from a patient with aspergilloma were investigated for azole resistance. The first cultured isolate showed a wild-type phenotype, but four azole-resistant phenotypes were observed in the subsequent eight isolates. Four mutations were found in the cyp51A gene of these isolates, leading to the substitutions A9T, G54E, P216L, and F219I. Only G54 substitutions were previously proved to be associated with azole resistance. Using a Cyp5 ...201222005994
the protective role of tlr6 in a mouse model of asthma is mediated by il-23 and il-17a.tlrs are a family of receptors that mediate immune system pathogen recognition. in the respiratory system, tlr activation has both beneficial and deleterious effects in asthma. for example, clinical data indicate that tlr6 activation exerts protective effects in asthma. here, we explored the mechanism or mechanisms through which tlr6 mediates this effect using mouse models of aspergillus fumigatus-induced and house dust mite antigen-induced (hdm antigen-induced) chronic asthma. tlr6-/- mice with ...201122005301
in vivo and in situ imaging of experimental invasive pulmonary aspergillosis using fibered confocal fluorescence microscopy.invasive pulmonary aspergillosis (ipa) is a highly fatal disease in immunosuppressed patients. in this study, we assessed fibered confocal fluorescence microscopy (fcfm), a new endoscopic technique that enables in vivo microscopic imaging of the distal lung, as a tool for in vivo imaging of ipa. ipa was induced in immunosuppressed rats using a wild strain of aspergillus fumigatus (n = 6) or a fluorescent transformed tag-rfp a. fumigatus strain (n = 10). subpleural areas of pulmonary infection we ...201122004362
Clinical implications of azole resistance in Aspergillus fumigatus, The Netherlands, 2007-2009.The prevalence and spread of azole resistance in clinical Aspergillus fumigatus isolates in the Netherlands are currently unknown. Therefore, we performed a prospective nationwide multicenter surveillance study to determine the effects of resistance on patient management strategies and public health. From June 2007 through January 2009, all clinical Aspergillus spp. isolates were screened for itraconazole resistance. In total, 2,062 isolates from 1,385 patients were screened; the prevalence of i ...201122000354
Analysis of phytochemical constituents of Eucalyptus citriodora L. responsible for antifungal activity against post-harvest fungi.In vitro antifungal activity and phytochemical constituents of essential oil, aqueous, methanol and chloroform extract of Eucalyptus citriodora Hook leaves were investigated. A qualitative phytochemical analysis was performed for the detection of alkaloids, cardiac glycosides, flavonoids, saponins, sterols, tannins and phenols. Methanolic extract holds all identified biochemical constituents except for the tannin. While these biochemical constituents were found to be absent in essential oil, aqu ...201121999598
analysis of volatile fingerprints for monitoring anti-fungal efficacy against the primary and opportunistic pathogen aspergillus fumigatus.the aims of this study were to use qualitative volatile fingerprints obtained using a hybrid sensor array system to screen anti-fungals for controlling the important lung infecting fungus, aspergillus fumigatus, especially in immunocompromised patients. sift-ms was also used to try and identify key volatiles produced by a. fumigatus. initial studies were carried out to identify the ed(50) and ed(90) (effective dose) for inhibiting growth of a. fumigatus using three anti-fungal compounds, benomyl ...201121997859
Culture-positive invasive aspergillosis in a medical center in Taiwan, 2000-2009.We reviewed 776 patients who were culture positive for Aspergillus species at the hospital from 2000 to 2009. The isolates were collected for species identification by oligonucleotide hybridization and sequence analysis. A total of 96 cases of proven or probable IA were identified according to published criteria. The incidence of IA has increased significantly during the study period. Aspergillus fumigatus and A. flavus (41.7% each) were equally prevalent causative species. IA due to unusual spe ...201121997774
[Pleiotropic drug resistance ABC transporters in fungi].Overexpression of pleiotropic drug resistance (PDR) efflux pumps of the ATP-binding cassette (ABC) transporter superfamily is the major cause of fungal multi-drug resistance and decreased efficacy of antifungal drugs. This review focused on recent progresses in understanding of the PDR efflux pumps of ABC transporter superfamily in Saccharomyces cerevisiae and the fungal pathogens Candida albicans, Cryptococcus neoformans, and Aspergillus fumigates. The mechanisms underlying efflux pump-mediated ...201121993279
vacuum-assisted closure and primary cutaneous aspergillosis in a burn - a management dilemma!the advent of vacuum-assisted closure (vac) devices has changed many wound management practices by application of topical negative pressure. a 20-year-old male sustained 21% total body surface area circumferential full-thickness burns to both legs from knees to feet. the vac dressing was used in the management of his wounds. the patient had persistent pyrexia and graft destruction and subsequently the wounds cultured aspergillus fumigatus. the increasing popularity of the vac dressing is well de ...201021991198
regeneration of centella asiatica plants from non-embryogenic cell lines and evaluation of antibacterial and antifungal properties of regenerated calli and plants.abstract:201121989222
synthesis and biological activity of ethyl 2-(substituted benzylthio)-4-(3'-(ethoxycarbonyl)biphenyl-4-yl)-6-methyl-1,4-dihydropyrimidine-5-carboxylate derivatives.in the present study, a new series of ethyl 2-(substituted benzylthio)-4-(3'-(ethoxycarbonyl)-biphenyl-4-yl)-6-methyl-1,4-dihydropyrimidine-5-carboxylate derivatives was synthesized. the newly synthesized compounds were characterized by (1) h-nmr, mass and c, h, n analyses. all newly synthesized compounds were screened for their antibacterial (escherichia coli, staphylococcus aureus, pseudomonas aeruginosa, streptococcus pyogenes and klebsiella pneumoniae) and antifungal (aspergillus flavus, asp ...201121987259
host defenses against cryptococcosis.the interaction of pathogenic cryptococcus species with their various hosts is somewhat unique compared to other fungal pathogens such as aspergillus fumigatus and candida albicans. cryptococcus shares an intimate association with host immune cells, leading to enhanced intracellular growth. furthermore, unlike most other fungal pathogens, the signs and symptoms of cryptococcal disease are typically self-inflicted by the host during the host's attempt to clear this invader from sensitive organ sy ...201121985306
Protein Glycosylation in Aspergillus fumigatus Is Essential for Cell Wall Synthesis and Serves as a Promising Model of Multicellular Eukaryotic Development.Glycosylation is a conserved posttranslational modification that is found in all eukaryotes, which helps generate proteins with multiple functions. Our knowledge of glycosylation mainly comes from the investigation of the yeast Saccharomyces cerevisiae and mammalian cells. However, during the last decade, glycosylation in the human pathogenic mold Aspergillus fumigatus has drawn significant attention. It has been revealed that glycosylation in A. fumigatus is crucial for its growth, cell wall sy ...201221977037
molecular detection and species-specific identification of medically important aspergillus species by real-time pcr in experimental invasive pulmonary aspergillosis.diagnosis of invasive pulmonary aspergillosis (ipa) remains a major challenge to clinical microbiology laboratories. we developed rapid and sensitive quantitative pcr (qpcr) assays for genus- and species-specific identification of aspergillus infections by use of taqman technology. in order to validate these assays and understand their potential diagnostic utility, we then performed a blinded study of bronchoalveolar lavage (bal) fluid specimens from well-characterized models of ipa with the fou ...201121976757
methylxanthine inhibit fungal chitinases and exhibit antifungal activity.chitinases are necessary for fungal cell wall remodeling and cell replication. methylxanthines have been shown to competitively inhibit family 18 chitinases in vitro. we sought to determine the effects of methylxanthines on fungal chitinases. fungi demonstrated variable chitinase activity and incubation with methylxanthines (0.5-10 mm) resulted in a dose-dependent decrease in this activity. all fungi tested, except for candida spp., demonstrated growth inhibition in the presence of methylxanthin ...201121968902
Differences in Efficacy and Cytokine Profiles following Echinocandin or Liposomal Amphotericin B Monotherapy or Combination Therapy for Murine Pulmonary or Systemic Aspergillus flavus Infections.Given the recent increase in aspergillosis caused by species other than Aspergillus fumigatus, micafungin, caspofungin, and liposomal amphotericin B (L-AmBi) were investigated as monotherapy or combination therapy for murine systemic or pulmonary Aspergillus flavus infection. Treatment for 3 or 6 days was begun at 24 h (intravenous [i.v.], 2.8 × 10(4) conidia) or 2 h (intranasal, 4.1 × 10(6) to 6.75 × 10(6) conidia) postchallenge as follows: 5 or 10 mg/kg L-AmBi, 10 mg/kg caspofungin, 15 mg/kg m ...201221968353
Antifungal activity of microbial secondary metabolites.Secondary metabolites are well known for their ability to impede other microorganisms. Reanalysis of a screen of natural products using the Caenorhabditis elegans-Candida albicans infection model identified twelve microbial secondary metabolites capable of conferring an increase in survival to infected nematodes. In this screen, the two compound treatments conferring the highest survival rates were members of the epipolythiodioxopiperazine (ETP) family of fungal secondary metabolites, acetylglio ...201121966496
immunopathology and immunogenetics of allergic bronchopulmonary aspergillosis.allergic bronchopulmonary aspergillosis (abpa) is a th2 hypersensitivity lung disease in response to aspergillus fumigatus that affects asthmatic and cystic fibrosis (cf) patients. sensitization to a. fumigatus is common in both atopic asthmatic and cf patients, yet only 1%-2% of asthmatic and 7%-9% of cf patients develop abpa. abpa is characterized by wheezing and pulmonary infiltrates which may lead to pulmonary fibrosis and/or bronchiectasis. the inflammatory response is characterized by th2 ...201121966295
Routine processing procedures for isolating filamentous fungi from respiratory sputum samples may underestimate fungal prevalence.Colonization of the airways by filamentous fungi can occur in asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis. A recent study found IgE sensitization to Aspergillus fumigatus to be associated with reduced lung function. Significantly higher rates of A. fumigatus were detected in sputum from asthmatics sensitized to this fungus compared to non-sensitized asthmatics. The rate of positive cultures was far higher than equivalent historical samples analysed by the local clini ...201121961802
glionitrin b, a cancer invasion inhibitory diketopiperazine produced by microbial coculture.a new diketopiperazine, glionitrin b (1), was produced using a microbial coculture of the fungus aspergillus fumigatus kmc-901 and the bacterium sphingomonas sp. kmk-001 that were isolated from acidic coal mine drainage. the structure of 1 was determined to be (3s,10as)-dithiomethylglionitrin a. this structure was determined by the analyses of extensive nmr data and the circular dichroism spectra of the natural product and a semisynthetic compound derived from glionitrin a. in contrast to glioni ...201121954885
Fluorinated s-triazinyl piperazines as antimicrobial agents.A series of 1,3,5-triazine derivatives that contain 4-amino-2-trifluoromethyl-benzonitrile, 8-hydroxyquinoline, and different piperazines as substituents at the carbon atoms of the triazine ring have been synthesized by a simple and efficient synthetic protocol. The chemical structures of the compounds were elucidated with the aid of IR, 1H NMR and 13C NMR spectroscopy, and elemental analysis. The antimicrobial activity of the compounds was tested against seven bacteria (Staphylococcus aureus MT ...201121950158
role of aspergillus lentulus 14-α sterol demethylase (cyp51a) in azole drug susceptibility.recent studies have demonstrated that some morphologically atypical aspergillus fumigatus strains are different species belonging to the section fumigati. aspergillus lentulus, one of these sibling species, is increasingly reported in patients under corticosteroid treatment. mics of most antifungals in clinical use are elevated against a. lentulus, and it shows primary resistance to azole drugs. two a. lentulus cytochrome p450 14-α sterol demethylases, encoded by a. lentulus cyp51a (alcyp51a) an ...201121947395
Evaluation of Aspergillus PCR protocols for testing serum specimens.A panel of human serum samples spiked with various amounts of Aspergillus fumigatus genomic DNA was distributed to 23 centers within the European Aspergillus PCR Initiative to determine analytical performance of PCR. Information regarding specific methodological components and PCR performance was requested. The information provided was made anonymous, and meta-regression analysis was performed to determine any procedural factors that significantly altered PCR performance. Ninety-seven percent of ...201121940479
in vitro antifungal activity of dna topoisomerase inhibitors.in this paper we report the results of the study of the in vitro effect of eight anticancer dna topoisomerase inhibitors on the growth of aspergillus fumigatus, a. niger, candida glabrata and cryptococcus neoformans. only one compound, idarubicin, displayed promising antifungal activity against a. niger, c. glabrata and c. neoformans with mic(50) values varying between 3.6 and 14.2 μm (1.8-7.1 μg/ml). three other compounds, aclarubicin, doxorubicin and mitoxantrone, showed some antifungal activi ...201121939347
azole antifungal resistance today: focus on aspergillus.oral triazole therapy is well established for the treatment of invasive aspergillosis (ipa), allergic aspergillosis (abpa), and chronic pulmonary aspergillosis (cpa), and is often long-term. resistance to triazole azole antifungal drugs in aspergillus fumigatus is now a major clinical problem in a number of european locations, in china, canada and the usa with particularly high frequencies from the north-west of the uk, and the netherlands. a number of centers are reporting the continuing increa ...201121931980
hsp90 governs dispersion and drug resistance of fungal biofilms.fungal biofilms are a major cause of human mortality and are recalcitrant to most treatments due to intrinsic drug resistance. these complex communities of multiple cell types form on indwelling medical devices and their eradication often requires surgical removal of infected devices. here we implicate the molecular chaperone hsp90 as a key regulator of biofilm dispersion and drug resistance. we previously established that in the leading human fungal pathogen, candida albicans, hsp90 enables the ...201121931556
significance of specific igg against sensitizing antigens in extrinsic allergic alveolitis: serological methods in eaa.the aim of our study is to find differences in igg in sera of potentially exposed and nonexposed individuals and to detect differences in concentrations of specific serum igg among subjects with and without eaa. seventy-two patients being followed for suspected interstitial lung disease were included. specific igg in sera were established by immunocap. serum concentrations of aspergillus fumigatus, candida albicans igg and mixture of moulds igg were higher in subjects with exposure to relevant i ...201121924863
pre-exposure of galleria mellonella larvae to different doses of aspergillus fumigatus conidia causes differential activation of cellular and humoral immune responses.larvae of galleria mellonella are useful models for studying the virulence of microbial pathogens or for evaluating the potency of antimicrobial agents. in this work we demonstrated that prior exposure of larvae to non-lethal doses of aspergillus fumigatus conidia increases the resistance of larvae to a lethal dose (1 x 10⁷ 20 μl⁻¹) 24 h later. exposure of larvae to a conidia concentration of 1 x 10⁴ 20 μl⁻¹ leads to an increase in haemocyte density but an inoculum of 1 x 10⁵ conidia leads to en ...201121921688
Monitoring and assessment of airborne fungi in Kolkata, India, by viable and non-viable air sampling methods.The composition and variability of airborne fungal spores were studied using two complementary sampling methods in an outdoor environment in Kolkata suburb for 2 years, from November 2002 to October 2004. For monitoring the total fungal spore burden in the air, Burkard 7-day volumetric sampler was used, whereas Andersen two-sage viable sampler was used for isolating the cultivable airborne fungi. Among the 37 fungal spore types identified in the air samples, the predominant ones were Cladosporiu ...201121915605
synergistic interaction of the triple combination of amphotericin b, ciprofloxacin, and polymorphonuclear neutrophils against aspergillus fumigatus.aspergillus is damaged by polymorphonuclear neutrophils (pmns) by means of nonoxidative and oxidative mechanisms, which may be affected by antifungal and antibacterial agents that patients with invasive pulmonary aspergillosis often receive. the pharmacodynamic interactions among deoxycholate amphotericin b (amb), ciprofloxacin (cip), and human pmns against aspergillus fumigatus growth are unknown. we therefore studied the interactions between 0.032 to 2.0 μg/ml of amb, 0.1 to 50 μg/ml of cip at ...201121911564
the structure-function relationship of the aspergillus fumigatuscyp51a l98h conversion by site-directed mutagenesis: the mechanism of l98h azole resistance.since 1998, the rapid emergence of multi-azole-resistance (mar) was observed in aspergillus fumigatus in the netherlands. two dominant mutations were found in the cyp51a gene, a 34bp tandem repeat (tr) in the promoter region combined with a leucine to histidine substitution at codon 98 (l98h). in this study, we show that molecular dynamics simulations combined with site-directed mutagenesis of amino acid substitutions in the cyp51a gene, correlate to the structure-function relationship of the l9 ...201121907818
Development of an efficient gene-targeting system in Aspergillus luchuensis by deletion of the non-homologous end joining system.The industrial fungus Aspergillus luchuensis is used to produce a distilled spirit in Okinawa Island, Japan. Recently, the genome sequence of A. luchuensis RIB2604 (Aspergillus awamori NBRC 4314) was revealed and many functional genes are now expected to be analyzed. Gene targeting is necessary for analyzing the function of a gene; however, gene targeting frequencies in A. luchuensis are very low. To develop a highly efficient gene-targeting system for A. luchuensis, we disrupted A. luchuensis l ...201121903470
Antifungal activity and chemical composition of essential oils from Smyrnium olusatrum L. (Apiaceae) from Italy and Portugal.The essential oils and supercritical CO(2) extracts of wild Smyrnium olusatrum L. growing in Sardinia (Italy) and in Portugal were investigated. For the study, oils were isolated from total plant aerial part (umbels containing seeds). The content of ß-phellandrene (67.3% vs. 42.7%) and a-pinene (31.9% vs. 1.2%), respectively, the main components of Portuguese and Italian essential oils, declined during the maturation stage of the umbels. Contrarily, some other important components, particularly ...201121902563
comparative study of fungal cell disruption--scope and limitations of the methods.simple and effective protocols of cell wall disruption were elaborated for tested fungal strains: penicillium citrinum, aspergillus fumigatus, rhodotorula gracilis. several techniques of cell wall disintegration were studied, including ultrasound disintegration, homogenization in bead mill, application of chemicals of various types, and osmotic shock. the release of proteins from fungal cells and the activity of a cytosolic enzyme, glucose-6-phosphate dehydrogenase, in the crude extracts were as ...201121901292
Complexity generation in fungal peptidyl alkaloid biosynthesis: oxidation of fumiquinazoline A to the heptacyclic hemiaminal fumiquinazoline C by the flavoenzyme Af12070 from Aspergillus fumigatus.The human pathogen Aspergillus fumigatus makes a series of fumiquinazoline (FQ) peptidyl alkaloids of increasing scaffold complexity using L-Trp, 2 equiv of L-Ala, and the non-proteinogenic amino acid anthranilate as building blocks. The FQ gene cluster encodes two non-ribosomal peptide synthetases (NRPS) and two flavoproteins. The trimodular NRPS Af12080 assembles FQF (the first level of complexity) while the next two enzymes, Af12060 and Af12050, act in tandem in an oxidative annulation sequen ...201121899262
formyl migration product of chanoclavine-i aldehyde in the presence of the old yellow enzyme fgaox3 from aspergillus fumigatus: a nmr structure elucidation.a previous study showed that together with the festuclavine synthase fgafs, the old yellow enzyme fgaox3 from aspergillus fumigatus catalyzed the conversion of chanoclavine-i aldehyde to festuclavine in the biosynthesis of ergot alkaloids. in the absence of fgafs, a mixture containing two compounds with a ratio of 7:3 was detected in the enzyme assay of fgaox3. nmr experiments including (dqf)-cosy, hsqc, hmbc and noesy identified their structures as e/z isomers of n-methyl-n-[(5r,10r)-10-(2-oxo- ...201121898587
[allergic bronchopulmonary mycosis due to schizophyllum commune and aspergillus fumigatus].a 53-year-old man who had been suffering from asthma presented to our hospital because of abnormal shadows detected on a chest x-ray film during a routine medical examination. a biopsy specimen of a mucus plug obtained by bronchoscopy showed fungal hyphae, eosinophils, and charcot-leyden crystals, with evidence of lung tissue eosinophilia. schizophyllum commune and aspergillus fumigatus were isolated from his sputum, bronchial washing specimens and the mucus plug. we detected specific immunoglob ...201121894779
detection of invasive candida albicans infection using a specific (99m)tc-labeled monoclonal antibody for the c. albicans germ tube.accurate diagnosis is critical for effective treatment of the invasive infection by candida albicans. here, we investigated whether a (99m) technetium (tc)-labeled fab' fragment of the monoclonal antibody specific for the c. albicans germ tube could specifically identify an invasive c. albicans infection. the germ tube of c. albicans was used as an immunogen to obtain monoclonal antibodies and the fab' fragment of mab03.2 c1-c2 with highest affinity and specificity was labeled with (99m)tc. in v ...201121894481
in vitro antifungal, anti-elastase and anti-keratinase activity of essential oils of cinnamomum-, syzygium- and cymbopogon-species against aspergillus fumigatus and trichophyton rubrum.this study was aimed to evaluate effects of certain essential oils namely cinnamomum verum, syzygium aromaticum, cymbopogon citratus, cymbopogon martini and their major components cinnamaldehyde, eugenol, citral and geraniol respectively, on growth, hyphal ultrastructure and virulence factors of aspergillus fumigatus and trichophyton rubrum. the antifungal activity of essential oils and their major constituents was in the order of cinnamaldehyde>eugenol>geraniol=c. verum>citral>s. aromaticum>c. ...201121893402
assembly of live micro-organisms on microstructured pdms stamps by convective/capillary deposition for afm bio-experiments.immobilization of live micro-organisms on solid substrates is an important prerequisite for atomic force microscopy (afm) bio-experiments. the method employed must immobilize the cells firmly enough to enable them to withstand the lateral friction forces exerted by the tip during scanning but without denaturing the cell interface. in this work, a generic method for the assembly of living cells on specific areas of substrates is proposed. it consists in assembling the living cells within the patt ...201121891839
microwave assisted synthesis and antimicrobial evaluation of new fused pyran derivatives bearing 2-morpholinoquinoline nucleus.a new series of fused pyran derivatives 5a-x bearing 2-morpholinoquinoline nucleus has been synthesized under microwave irradiation by a reaction of 2-morpholinoquinoline-3-carbaldehyde 2a-c, malononitrile 3 and compounds 4a-h in presence of naoh as basic catalyst. all the compounds were screened against three gram positive bacteria (streptococcus pneumoniae, clostridium tetani, bacillus subtilis), three gram negative bacteria (salmonella typhi, vibrio cholerae, escherichia coli) and two fungi ( ...201121890359
systems biology of infectious diseases: a focus on fungal infections.the study of infectious disease concerns the interaction between the host species and a pathogen organism. the analysis of such complex systems is improving with the evolution of high-throughput technologies and advanced computational resources. this article reviews integrative, systems-oriented approaches to understanding mechanisms underlying infection, immune response and inflammation to find biomarkers of disease and design new drugs. we focus on the systems biology process, especially the d ...201121889228
the map kinase mpka controls cell wall integrity, oxidative stress response, gliotoxin production and iron adaptation in aspergillus fumigatus.the saprophytic fungus aspergillus fumigatus is the most important air-borne fungal pathogen. the cell wall of a. fumigatus has been studied intensively as a potential target for development of effective antifungal agents. a major role in maintaining cell wall integrity is played by the mitogen-activated protein kinase (mapk) mpka. to gain a comprehensive insight into this central signal transduction pathway, we performed a transcriptome analysis of the δmpka mutant under standard and cell wall ...201121883519
evaluation of luminex xtag fungal analyte-specific reagents for rapid identification of clinically relevant fungi.invasive fungal infections (ifi) remain a serious threat to immunocompromised hosts. current diagnostic methods, including fungal culture and antigen detection, are slow and often lack specificity. rapid diagnostic tools with increased sensitivity and specificity could improve the care of patients with ifi. recently, luminex molecular diagnostics (toronto, canada) developed 23 analyte-specific reagents (asrs) for the detection of the most common clinically relevant fungi. this study's objective ...201121880976
Determining the limits and confounders for the 2-pentyl furan breath test by gas chromatography/mass spectrometry.Aspergillus fumigatus produces 2-pentyl furan (2-PF), a volatile compound not produced by many other pathogens or normal human metabolism. 2-Pentyl furan has been detected in the breath of patients with invasive aspergillosis (IA) by SPME pre-concentration coupled with CG/MS providing the possibility of an attractive diagnostic test. The limit of detection (LOD) and quantification (LOQ) for peak integration were assessed both statistically and empirically respectively. 2-Pentyl furan was detecte ...201121880557
Single-pot derivatisation strategy for enhanced gliotoxin detection by HPLC and MALDI-ToF mass spectrometry.Gliotoxin is produced by non-ribosomal peptide synthesis and secreted from certain fungi, including Aspergillus fumigatus. It is an epipolythiodioxopiperazine that contains an intact disulphide bridge and is the focus of intense research as a consequence of its negative immunomodulatory properties. Gliotoxin detection is generally enabled by reversed-phase-high-performance liquid chromatography (RP-HPLC), with absorbance detection (220-280 nm), or liquid chromatography-mass spectrometry, yet det ...201121879298
fluorescence polarization binding assay for aspergillus fumigatus virulence factor udp-galactopyranose mutase.aspergillus fumigatus is an opportunistic human pathogenic fungus responsible for deadly lung infections in immunocompromised individuals. galactofuranose (galf) residues are essential components of the cell wall and play an important role in a. fumigatus virulence. the flavoenzyme udp-galactopyranose mutase (ugm) catalyzes the isomerization of udp-galactopyranose to udp-galactofuranose, the biosynthetic precursor of galf. thus, inhibitors of ugm that block the biosynthesis of galf can lead to n ...201121876791
Interrogation of related clinical pan-azole-resistant Aspergillus fumigatus strains: G138C, Y431C, and G434C single nucleotide polymorphisms in cyp51A, upregulation of cyp51A, and integration and activation of transposon Atf1 in the cyp51A promoter.Multiple Aspergillus fumigatus isolates from a patient with two aspergillomas complicating chronic pulmonary aspergillosis were pan-azole resistant. Microsatellite typing was identical for all isolates despite major phenotypic and some growth rate differences. Three different cyp51A mutations were found (G138C, Y431C, and G434C), of which the first two were demonstrated by heterologous expression in a hypersusceptible Saccharomyces cerevisiae strain to be at least partly responsible for elevated ...201121876055
necessary and sufficient role for t helper cells to prevent fungal dissemination in allergic lung disease.mucosal immune responses to fungal infection range from t helper type 2 (th2) cell-directed allergic inflammation to th1-predominant neutrophilic inflammation, but the mechanisms directing these divergent mucosal immune outcomes and the role of t cells in host defense against mucosal fungal infections are not known. here we examined the mouse mucosal immune responses to 12 filamentous environmental fungal species over a broad range of exposure doses and determined the requirement of t cells for ...201121875960
diffuse myelitis after treatment of cerebral aspergillosis in an immune competent patient.presentation of an unusual case of cerebral aspergillosis in an immune competent patient who was treated successfully but symptoms and signs of a demyelinating process following initial recovery has been occurred. a 29-year-old male with focal seizure. brain mri revealed small multiple hemispheric and dural lesions. an open biopsy was conducted. histological evaluation revealed hyphe-like structure in the necrotic area, within vessel walls, and lumina, suggestive aspergillus fumigatus . furtherm ...201121874647
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