Stimulating encounter: The intimate, physical interaction between the soil-derived bacterium Streptomyces rapamycinicus and the human pathogenic fungus Aspergillus fumigatus led to the activation of an otherwise silent polyketide synthase (PKS) gene cluster coding for an unusual prenylated polyphenol (fumicycline A). The meroterpenoid pathway is regulated by a pathway-specific activator gene as well as by epigenetic factors.. ...
A. fumigatus strains and culture conditions: A. fumigatus strains used in this study are listed in Table 1. A. fumigatus strains were propagated at 37° on complete medium or minimal medium (MM) with 0.5 mm of one of the following nitrogen sources: sodium glutamate, ammonium tartrate, sodium nitrate, sodium nitrite, or hypoxanthine (Cove 1966). Uridine and uracil were added at a concentration of 5 mm when appropriate. Selection of A. fumigatus mutants unable to utilize nitrate as the sole nitrogen source was obtained by plating spores on MM containing ammonium tartrate and 100 mm sodium chlorate (Cove 1966). The nature of the mutation was assessed by growth on MM supplemented with different nitrogen sources, as previously described (Cove 1976). Selection of A. fumigatus mutants auxotrophic for uridine and uracil was achieved on MM containing 1 mg/ml 5-fluoroorotic acid plus uridine and uracil (dEnfert 1996). Liquid cultures used for DNA-mediated transformation and genomic DNA preparation were ...
Sphingolipids (SPLs) are key components of the plasma membrane in yeast and filamentous fungi. These molecules are involved in a number of cellular processes, and particularly, SGLs are essential components of the highly polarized fungal growth where they are required for the formation of the polarisome organization at the hyphal apex. Aspergillus fumigatus, a human fungal pathogen, produce SGLs that are discriminated into neutral cerebrosides, glycosylinositolphosphoceramides (GIPCs) and glycosylphosphatidylinositol (GPI) anchors. In addition to complex hydrophilic head groups of GIPCs, A. fumigatus is, to date, the sole fungus that produces a GPI-anchored polysaccharide. These SPLs follow three different biosynthetic pathways. Genetics blockage leading to the inhibition of any SPL biosynthesis or to the alteration of the structure of SPL induces growth and virulence defects. The complete lipid moiety of SPLs is essential for the lipid microdomain organization and their biosynthetic pathways are
Filamentous fungi represent classical examples for environmentally acquired human pathogens whose major virulence mechanisms are likely to have emerged long before the appearance of innate immune systems. In natural habitats, amoeba predation could impose a major selection pressure towards the acquisition of virulence attributes. To test this hypothesis, we exploited the amoeba Dicytostelium discoideum to study its interaction with Aspergillus fumigatus, two abundant soil inhabitants for which we found co-occurrence in various sites. Fungal conidia were efficiently taken up by D. discoideum, but ingestion was higher when conidia were devoid of the green fungal spore pigment DHN-melanin, in line with earlier results obtained for immune cells. Conidia were able to survive phagocytic processing and intracellular germination was initiated only after several hours of coincubation which eventually led to a lethal disruption of the host cell. Besides phagocytic interactions, both amoeba and fungus ...
Link to Pubmed [PMID] - 28677124. Mol. Microbiol. 2017 Sep;105(6):880-900. Aspergillus fumigatus, a ubiquitous human fungal pathogen, produces asexual spores (conidia), which are the main mode of propagation, survival and infection of this human pathogen. In this study, we present the molecular characterization of a novel regulator of conidiogenesis and conidial survival called MybA because the predicted protein contains a Myb DNA binding motif. Cellular localization of the MybA::Gfp fusion and immunoprecipitation of the MybA::Gfp or MybA::3xHa protein showed that MybA is localized to the nucleus. RNA sequencing data and a uidA reporter assay indicated that the MybA protein functions upstream of wetA, vosA and velB, the key regulators involved in conidial maturation. The deletion of mybA resulted in a very significant reduction in the number and viability of conidia. As a consequence, the ΔmybA strain has a reduced virulence in an experimental murine model of aspergillosis. RNA-sequencing and ...
The opportunistic human pathogen Aspergillus fumigatus initiates invasive growth through a programmed germination process that progresses from dormant spore to swollen spore (SS) to germling (GL) and ultimately invasive hyphal growth. We find a lipoxygenase with considerable homology to human Alox5 and Alox15, LoxB, that impacts the transitions of programmed spore germination. Overexpression of loxB (OE::loxB) increases germination with rapid advance to the GL stage. However, deletion of loxB (ΔloxB) or its signal peptide only delays progression to the SS stage in the presence of arachidonic acid (AA); no delay is observed in minimal media. This delay is remediated by the addition of the oxygenated AA oxylipin 5-hydroxyeicosatetraenoic acid (5-HETE) that is a product of human Alox5. We propose that A. fumigatus acquisition of LoxB (found in few fungi) enhances germination rates in polyunsaturated fatty acid-rich environments.
We present the genome sequences of a new clinical isolate of the important human pathogen, Aspergillus fumigatus, A1163, and two closely related but rarely pathogenic species, Neosartorya fischeri NRRL181 and Aspergillus clavatus NRRL1. Comparative genomic analysis of A1163 with the recently sequenced A. fumigatus isolate Af293 has identified core, variable and up to 2% unique genes in each genome. While the core genes are 99.8% identical at the nucleotide level, identity for variable genes can be as low 40%. The most divergent loci appear to contain heterokaryon incompatibility (het) genes associated with fungal programmed cell death such as developmental regulator rosA. Cross-species comparison has revealed that 8.5%, 13.5% and 12.6%, respectively, of A. fumigatus, N. fischeri and A. clavatus genes are species-specific. These genes are significantly smaller in size than core genes, contain fewer exons and exhibit a subtelomeric bias. Most of them cluster together in 13 chromosomal islands, ...
TY - JOUR. T1 - A Conserved C-Terminal Domain of the Aspergillus fumigatus Developmental Regulator MedA Is Required for Nuclear Localization, Adhesion and Virulence. AU - Al Abdallah, Qusai. AU - Choe, Se In. AU - Campoli, Paolo. AU - Baptista, Stefanie. AU - Gravelat, Fabrice N.. AU - Lee, Mark J.. AU - Sheppard, Donald C.. PY - 2012/11/21. Y1 - 2012/11/21. N2 - MedA is a developmental regulator that is conserved in the genome of most filamentous fungi. In the pathogenic fungus Aspergillus fumigatus MedA regulates conidiogenesis, adherence to host cells, and pathogenicity. The mechanism by which MedA governs these phenotypes remains unknown. Although the nuclear import of MedA orthologues has been reported in other fungi, no nuclear localization signal, DNA-binding domain or other conserved motifs have been identified within MedA. In this work, we performed a deletion analysis of MedA and identified a novel domain within the C-terminal region of the protein, designated MedA346-557, that is ...
The production of toxins by A. fumigatus may help the fungus to colonize and invade the respiratory epithelium by modifying the natural clearance of the respiratory tract. Previous research has shown that A. fumigatus culture filtrate modifies the transepithelial resistance (Rt) and transepithelial potential differences (Vt) of HNEC, an in vitro model of the air-liquid interface of airway epithelium [11]. The aim of this study was to use HPLC and MS-MS to identify which toxins produced by A. fumigatus are responsible for these modifications. Our data suggest that verruculogen, which has never been implicated in invasive aspergillosis, is one of the probable candidates.. The fact that A. fumigatus produces a number of biologically active substances that slow ciliary beating, damage epithelium, and that may affect colonization of the airways has already been reported using culture explants [17]. Among these substances, such toxins as gliotoxin, fumagillin, and helvolic acid have been implicated in ...
A new epimer of azaphilone derivative pinophilin B, epi-pinophilin B (1), and three known analogues (2-4) were obtained from the culture of the gorgonian-derived fungus Aspergillus fumigatus 14-27. The structures of 1-4, including their relative configurations were determined by extensive spectroscopic analysis and comparing with literature data. The absolute configuration of 1 was determined by electronic circular dichroism (ECD) and optical rotatory (OR) calculations methods. Compounds 1-4 were isolated from A. fumigatus for the first time. Their antibacterial and cytotoxic activities were also evaluated. PMID: 31564133 [PubMed - as supplied by publisher]. Source: Industry. ...
Melanins, or melanin-like compounds, may play a role in the pathogenesis of a number of human fungal infections. This study investigated the production of melanin by the important opportunistic pathogen Aspergillus fumigatus. Conidia from A. fumigatus were harvested and treated with proteolytic enzymes, denaturant and hot, concentrated acid; this yielded dark particles which were similar in size and shape to the original propagules. Electron spin resonance spectroscopy revealed that the conidial-derived particles were stable free radicals consistent with an identification as melanin. Melanin particles were used to immunize BALB/c mice in order to produce a total of five anti-melanin monoclonal antibodies (mAbs). The latter mAbs were strongly reactive both with intact conidia and with extracted melanin particles by ELISA and immunofluorescence reactivity. Immunofluorescence labelling with the novel mAbs was used to examine the temporal expression of melanin during in vitro culture of A. fumigatus
TY - JOUR. T1 - Biosynthesis of β-(1→5)-galactofuranosyl chains of fungal-type and o-mannose-type galactomannans within the invasive pathogen aspergillus fumigatus. AU - Chihara, Yuria. AU - Tanaka, Yutaka. AU - Izumi, Minoru. AU - Hagiwara, Daisuke. AU - Watanabe, Akira. AU - Takegawa, Kaoru. AU - Kamei, Katsuhiko. AU - Shibata, Nobuyuki. AU - Ohta, Kazuyoshi. AU - Oka, Takuji. PY - 2020/1/1. Y1 - 2020/1/1. N2 - ABSTRACT The pathogenic fungus Aspergillus fumigatus contains galactomannans localized on the surface layer of its cell walls, which are involved in various biological processes. Galactomannans comprise α-(1→2)-/α-(1→6)-mannan and β-(1→5)-/ β-(1→6)-galactofuranosyl chains. We previously revealed that GfsA is a β-galactofuranoside β-(1→5)-galactofuranosyltransferase involved in the biosynthesis of β-(1→5)-galactofuranosyl chains. In this study, we clarified the biosynthesis of β-(1→5)-galactofuranosyl chains in A. fumigatus. Two paralogs exist within A. ...
Land, C.J.; Sostarić, B.; Fuchs, R.; Lundström, H.; Hult, K., 1989: Intratracheal exposure of rats to Aspergillus fumigatus spores isolated from sawmills in Sweden
In this experiment, the OD value of different concentrations of Aspergillus fumigatus cultured for 48 hours was measured on a microplate reader using a 96-well plate. The absorbance-concentration curve was plotted according to the results, and the absorbance value was used instead of visual observation to quickly detect the growth of Aspergillus fumigatus. situation. The results showed that the OD value was between 0.05 and 0.06 when visually 50%, and 100% when the OD value was greater than 0.17. The use of the OD value can be a rapid method for observing the growth of Aspergillus fumigatus, which has the advantages of high efficiency, accuracy and high throughput compared with the visual method.. ...
The pharmacodynamics (PD) of liposomal amphotericin B (L-AMB) remain relatively poorly understood because of complex pharmacokinetics (PK) that impede the in-depth comprehension of its exposure-response relationship (1). Although high L-AMB doses up to 15 mg/kg have been used (2), in the absence of a clinical dose-response relationship a dose of 3 mg/kg is generally recommended for the treatment of invasive aspergillosis (IA) (1), with an end-of-treatment favorable response of ∼40% for probable/proven cases (3). However, neutropenia may affect the clinical response to L-AMB therapy (4). We therefore studied L-AMB PD in an in vitro PK/PD model using previously published data of experimental aspergillosis in neutropenic and nonneutropenic animal models and optimized L-AMB therapy simulating human serum concentration-time profiles against azole-susceptible and azole-resistant Aspergillus fumigatus isolates in neutropenic and nonneutropenic patients.. Two clinical A. fumigatus isolates, a ...
Glycoinositolphosphoceramides (GIPCs) are complex sphingolipids present at the plasma membrane of various eukaryotes with the important exception of mammals. In fungi, these glycosphingolipids commonly contain an alpha-mannose residue (Man) linked at position 2 of the inositol. However, several pathogenic fungi additionally synthesize zwitterionic GIPCs carrying an alpha-glucosamine residue (GlcN) at this position. In the human pathogen Aspergillus fumigatus, the GlcNalpha1,2IPC core (where IPC is inositolphosphoceramide) is elongated to Manalpha1,3Manalpha1,6GlcNalpha1,2IPC, which is the most abundant GIPC synthesized by this fungus. In this study, we identified an A. fumigatus N-acetylglucosaminyltransferase, named GntA, and demonstrate its involvement in the initiation of zwitterionic GIPC biosynthesis. Targeted deletion of the gene encoding GntA in A. fumigatus resulted in complete absence of zwitterionic GIPC; a phenotype that could be reverted by episomal expression of GntA in the mutant. ...
Host-pathogen interactions have critical implications for the establishment of disease and for determining adaptive immune responses of the host. This study has conducted global Aspergillus fumigatus transcriptional analyses throughout the initiation of murine infection using a wild-type and an attenuated ΔlaeA isolate. A novel data analysis protocol was applied from which three time-series datasets were generated between 4, 8 and 14 hours post infection. This approach identified distinct temporal gene expression profiles during disease initiation whereby numerous secreted enzymes, including proteases and antigens, were upregulated between 4 and 8 hours, while a striking upregulation of genes in secondary metabolism clusters and subtelomeric loci was observed between 8 and 14 hours. In order to test the role of several upregulated secondary metabolite genes on host-pathogen interactions and virulence, two isolates mutated in non-ribosomal peptide synthetase encoding genes (ΔftmA, Δpes3), and ...
The opportunistic fungal pathogen Aspergillus fumigatus is the causative agent of more than 90% of all Invasive Aspergillosis (IA) infections diagnosed in immun...
Abstract Sulphur is an essential element that all pathogens have to absorb from their surroundings in order to grow inside their infected host. Despite its importance, the relevance of sulphur assimilation in fungal virulence is largely unexplored. Here we report a role of the bZIP transcription factor MetR in sulphur assimilation and virulence of the human pathogen Aspergillus fumigatus. The MetR regulator is essential for growth on a variety of sulphur sources; remarkably, it is fundamental for assimilation of inorganic S-sources but dispensable for utilization of methionine. Accordingly, it strongly supports expression of genes directly related to inorganic sulphur assimilation but not of genes connected to methionine metabolism. On a broader scale, MetR orchestrates the comprehensive transcriptional adaptation to sulphur-starving conditions as demonstrated by digital gene expression analysis. Surprisingly, A. fumigatus is able to utilize volatile sulphur compounds produced by its methionine ...
1. KornitzerD 2009 Fungal mechanisms for host iron acquisition. Current opinion in microbiology 12 377 383. 2. SchrettlMBeckmannNVargaJHeinekampTJacobsenID 2010 HapX-mediated adaption to iron starvation is crucial for virulence of Aspergillus fumigatus. PLoS Pathog 6 e1001124 doi:10.1371/journal.ppat.1001124. 3. SchrettlMIbrahim-GranetODroinSHuerreMLatgeJP 2010 The crucial role of the Aspergillus fumigatus siderophore system in interaction with alveolar macrophages. Microbes and infection/Institut Pasteur 12 1035 1041. 4. SchrettlMBignellEKraglCSabihaYLossO 2007 Distinct roles for intra- and extracellular siderophores during Aspergillus fumigatus infection. PLoS Pathog 3 e128 doi:10.1371/journal.ppat.0030128. 5. SchrettlMBignellEKraglCJoechlCRogersT 2004 Siderophore biosynthesis but not reductive iron assimilation is essential for Aspergillus fumigatus virulence. The Journal of experimental medicine 200 1213 1219. 6. HissenAHChowJMPintoLJMooreMM 2004 Survival of Aspergillus fumigatus in serum ...
While azole drugs targeting the biosynthesis of ergosterol are effective antifungal agents, their extensive use has led to the development of resistant organisms. Infections involving azole resistant forms of the filamentous fungus Aspergillus fumigatus are often associated with genetic changes in the cyp51A gene encoding the lanosterol α14 demethylase target enzyme. Both a sequence duplication in the cyp51A promoter (TR34) as well as a substitution mutation in the coding sequence (L98H) are required for full expression of azole resistance. A mechanism commonly observed in pathogenic yeast such as Candida albicans involves gain-of-function mutations in transcriptional regulatory proteins that induce expression of ATP-binding cassette (ABC) transporter encoding genes. We and others have found that an ABC transporter protein called Cdr1B (here referred to as AbcG1) is required for wild-type azole resistance in A.fumigatus Here we test the genetic relationship between the TR34 L98H allele of ...
Aspergillus fumigatus ATCC ® 1022D-2™ Designation: Genomic DNA from Aspergillus fumigatus Strain 118 [ATCC ® 1022™] Application:
Aspergillus fumigatus Z5 has a strong ability to decompose lignocellulose biomass, and its extracellular protein secretion has been reported in earlier studies employing traditional techniques. However, a comprehensive analysis of its secretion in the presence of different carbon sources is still lacking. The goal of this work was to identify, quantify and compare the secretome of A. fumigatus Z5 in the presence of different carbon sources to understand in more details the mechanisms of lignocellulose decomposition by Aspergillus fumigatus Z5. Cellulolytic A. fumigatus Z5 was grown in the presence of glucose (Gl), Avicel (Av) and rice straw (RS), and the activities of several lignocellulosic enzymes were determined with chromatometry method. The maximum activities of endoglucanase, exoglucanase, β-glucosidase, laminarinase, lichenase, xylanase and pectin lyase were 12.52, 0.59, 2.30, 2.37, 1.68, 15.02 and 11.40 U·ml-1, respectively. A total of 152, 125 and 61 different proteins were identified in the
Filamentous fungi are an important cause of pulmonary and systemic morbidity and mortality, and also cause corneal blindness and visual impairment worldwide. Utilizing in vitro neutrophil killing assays and a model of fungal infection of the cornea, we demonstrated that Dectin-1 dependent IL-6 production regulates expression of iron chelators, heme and siderophore binding proteins and hepcidin in infected mice. In addition, we show that human neutrophils synthesize lipocalin-1, which sequesters fungal siderophores, and that topical lipocalin-1 or lactoferrin restricts fungal growth in vivo. Conversely, we show that exogenous iron or the xenosiderophore deferroxamine enhances fungal growth in infected mice. By examining mutant Aspergillus and Fusarium strains, we found that fungal transcriptional responses to low iron levels and extracellular siderophores are essential for fungal growth during infection. Further, we showed that targeting fungal iron acquisition or siderophore biosynthesis by ...
Aspergillus fumigatus is the most common airborne fungal pathogen of humans, causing life-threatening invasive disease in immunocompromised patients. The limitations of therapeutic intervention are reflected in mortality rates, dependent primarily on the immune status of the host, of up to 90% (1, 2). The importance of the host immune status has been underlined by the lack of identified specific virulence attributes in A. fumigatus (1, 3-6). Limiting access to essential nutrients is an often overlooked aspect of innate immunity (7). Iron is essential for most organisms, suggesting that its acquisition in vivo may be required for A. fumigatus to cause disease (8-10). Iron uptake systems are often required for bacterial and yeast virulence (11, 12).. Fungi have evolved various strategies, often used in parallel, to acquire iron. These include two high affinity uptake mechanisms, reductive iron assimilation, and siderophore-assisted iron mobilization (8-10). Siderophores are low molecular mass, ...
Invasive aspergillosis is a life-threatening disease, and its incidence has increased in the recent past. Dectin-1 recognizes β-glucans and mediates innate immune responses to Aspergillus fumigatus. Transcription factor PU.1 has been the focus of recent research due to its role in inflammation and infection. However, its role in Dectin-1 regulation during A. fumigatus infection remains to be elucidated. THP-1 cells were stimulated with A. fumigatus conidia. We then used real-time RT-PCR, Western blot, and immunofluorescence assays to analyze the mRNA and protein levels and cellular distribution, respectively, of Dectin-1 and PU.1 in stimulated THP-1 cells. Additionally, we used the luciferase reporter assays, chromatin immunoprecipitation (ChIP) assays, electrophoretic mobility shift assays (EMSA), and RNA interference experiments to investigate the role of PU.1 in Dectin-1 regulation. Our results revealed that Dectin-1 mRNA and protein levels as well as the PU.1 protein level were increased in THP-1
Aspergillus fumigatus is considered a common causative agent of human fungal infections. A restricted number of virulence factors have been described, and none of them lead to a differentiation in the virulence level among different strains. Variations in the virulence phenotype depending on the isolate origin, measured as survival percentage in animal infection models, have been previously reported. In this study, we analyzed the whole-genome sequence of A. fumigatus isolates from clinical and environmental origins to determine their virulence genetic content. The sample included four isolates sequenced at the University Medical Center Groningen (UMCG), three clinical (two of them isolated from the same patient) and the experimental strain B5233, and the draft genomes of one reference strain, two environmental and two clinical isolates obtained from a public database. The fungal genomes were screened for the presence of virulence-related genes (VRGs) using an in-house database of 244 genes related to
Sensitization to Aspergillus fumigatus as a risk factor for bronchiectasis in COPD Stephanie Everaerts,1,2 Katrien Lagrou,3,4 Adriana Dubbeldam,5 Natalie Lorent,1 Kristina Vermeersch,2 Erna Van Hoeyveld,3 Xavier Bossuyt,3,4 Lieven J Dupont,1,2 Bart M Vanaudenaerde,2 Wim Janssens1,2 1Department of Respiratory Diseases, University Hospitals Leuven, 2Laboratory of Respiratory Diseases, Department of Clinical and Experimental Medicine, KU Leuven, 3Department of Laboratory Medicine, University Hospitals Leuven, 4Department of Microbiology and Immunology, KU Leuven, 5Department of Radiology, University Hospitals Leuven, Leuven, Belgium Background: Bronchiectasisâ chronic obstructive pulmonary disease (COPD) overlap presents a possible clinical phenotype of COPD, but it is unclear why it develops in a subset of patients. We hypothesized that sensitization to Aspergillus fumigatus (A fum) is associated with bronchiectasis in COPD and occurs more frequently in vitamin D-deficient patients.Methods: This
Aspergillus fumigatus is a thermotolerant human-pathogenic mold and the most common cause of invasive aspergillosis (IA) in immunocompromised patients. Its predominance is based on several factors most of which are still unknown. The thermotolerance of A. fumigatus is one of the traits which have been assigned to pathogenicity. It allows the fungus to grow at temperatures up to and above that of a fevered human host. To elucidate the mechanisms of heat resistance, we analyzed the change of the A. fumigatus proteome during a temperature shift from 30°C to 48°C by 2D-fluorescence difference gel electrophoresis (DIGE). To improve 2D gel image analysis results, protein spot quantitation was optimized by missing value imputation and normalization. Differentially regulated proteins were compared to previously published transcriptome data of A. fumigatus. The study was augmented by bioinformatical analysis of transcription factor binding sites (TFBSs) in the promoter region of genes whose corresponding
Pseudomonas aeruginosa and Aspergillus fumigatus are the two microorganisms responsible for most of the chronic infections in cystic fibrosis patients. P.
Metal restriction imposed by mammalian hosts during an infection is a common mechanism of defence to reduce or avoid the pathogen infection. Metals are essential for organism survival due to its involvement in several biological processes. Aspergillus fumigatus causes invasive aspergillosis, a disea …
Invasive aspergillosis is a life-threatening and difficult to treat infection in immunosuppressed patients. The efficacy of current anti-Aspergillus therapies, targeting the cell wall or membrane, is limited by toxicity (polyenes), fungistatic activity and some level of basal resistance (echinocandins), or the emergence of acquired resistance (triazoles). The heat shock protein 90 (Hsp90) is a conserved molecular chaperone involved in the rapid development of antifungal resistance in the yeast Candida albicans. Few studies have addressed its role in filamentous fungi such as Aspergillus fumigatus, in which mechanisms of resistance may differ substantially. Hsp90 is at the center of a complex network involving calcineurin, lysine deacetylases (KDAC) and other client proteins, which orchestrate compensatory repair mechanisms of the cell wall in response to the stress induced by antifungals. In A. fumigatus, Hsp90 is a trigger for resistance to high concentrations of caspofungin, known as
Modern medical technologies are repairing the human body in ways never imagined only a few years ago, but they are leaving an increasing population of patients who are newly susceptible to opportunistic pathogens. Invasive and chronic fungal infections have become a formidable clinical opponent, and foremost among them is Aspergillus fumigatus. Aspergillusfumigatus and Aspergillosis assembles chapters from a large and international contingent of experts in the field to explore every major aspect of A. fumigatus and how it kills so many patients. This volume offers the latest insights into the fundamental biology and pathogenesis of A. fumigatus and how it establishes disease, as well as the newest strategies for characterizing, diagnosing, and treating its spectrum of clinical infection. This valuable book is an instrumental resource for both scientists and clinicians tackling the current problems with Aspergillosis. It presents chapters on the species itself, including morphology and unique and
Purpose: Calcineurin orchestrates growth, stress responses and virulence in major pathogenic fungi including Aspergillus fumigatus responsible for life-threatening fungal infections worldwide. While these cellular regulatory functions of calcineurin make it an attractive antifungal target, the immunosuppressive effects of the currently available calcineurin inhibitors, FK506 and CsA, make it difficult to exploit the antifungal potential due to conservation of calcineurin in the host and the fungal pathogen. Critical molecular understanding of calcineurin-immunophilin-immunosuppressor complexes would facilitate the design of novel non-immunosuppressive CsA and FK506 analogs for fungal-specific targeting of calcineurin.. Methods: We solved the crystal structure of calcineurin-FK506-FKBP12 complex in A. fumigatus and using site-directed mutagenic approaches, we constructed several mutations in the CnaA catalytic subunit of calcineurin and FKBP12. To identify differences between the A. fumigatus ...
Personal exposures to A. fumigatus are associated with a variety of adverse health outcomes, including invasive aspergillosis, allergic sensitization, and asthma. Due to the high rate of mortality associated with invasive disease in immunocompromised patients, most studies of A. fumigatus have aimed to characterize the immune responses in immunocompromised murine models. However, a larger portion of the population is affected by fungal-induced allergies and asthma and the immune mechanisms associated with exposure have rarely been studied in an immunocompetent model. These models do not accurately reflect the natural method of exposure to environmental sources of conidia, and may significantly impact responses between fungi and the host immune system. Furthermore, little is known about the mechanisms associated with fungal induced allergy and asthma. Persistence of antigen is believed to play a role in induction of these diseases. Melanin, an A. fumigatus virulence factor, protects conidia from innate
The SREBP SrbA in A. fumigatus has previously been shown to be required for hypoxia and low-iron adaptation, triazole drug susceptibility, and virulence (4, 5, 47). Given the potential importance of SrbA in fungal virulence and responses to antifungal therapy, a further examination of the mechanisms of SrbA regulation and function is warranted in A. fumigatus. SREBPs exist as precursor proteins that are cleaved to release the active N terminus transcription factor (8). In A. fumigatus, whether SrbA required proteolytic processing for function as a transcription factor was unclear. Bioinformatic analyses of the SrbA amino acid sequence strongly suggest that SrbA is an integral membrane protein like SREBPs in other organisms. Here, we observed that the GFP signal from an SrbA:GFP fusion protein strain largely localizes to the nuclear envelope/ER membrane, supporting the bioinformatics data with regard to SrbA localization in A. fumigatus. However, previous attempts to identify the sterol cleavage ...
2005. The Aspergillus nidulans phytochrome FphA represses sexual development in red light. Curr. Biol. 15:1833-1838. Casselton, L. A. 2002. Mate recognition in fungi. Heredity 88:142- 147. , J. P. Debeaupuis, J. Sarfati, J. Lortholary, P. Ribaud, P. Shah, M. Cornet, H. V. Thien, E. Gluckman, G. Bru ¨cker, and J. P. Latge´. 1998. Molecular typing of environmental and patient isolates of Aspergillus fumigatus from various hospital settings. J. Clin. Microbiol. 36:1494-1500. Debeaupuis, J. , J. Sarfati, V. Momany, T. Tanaka, T. Kumagai, K. Asai, M. Machida, W. C. Nierman, D. W. Denning, M. Caddick, M. Hynes, M. Paoletti, R. Fischer, B. Miller, P. Dyer, M. S. Sachs, S. A. Osmani, and B. W. Birren. 2005. Sequencing and comparative analysis of Aspergillus nidulans. Nature 438:1105-1115. , M. Christensen, A. H. Onions, J. I. Pitt, and R. A. Samson. 1985. Infrageneric taxa of Aspergillus, p. 55-62. In R. A. Samson and J. I. ), Advances in Penicillium and Aspergillus Systematics. Plenum Press, New ...
Aspergillus fumigatus is the main cause of invasive aspergillosis in immunocompromised patients, and only a limited number of drugs for treatment are available. A screening method for new antifungal compounds is urgently required, preferably an appro
Objective: To report the cases of 6 patients with fungus ball caused by Aspergillus fumigatus (aspergilloma) in the pleural cavity. Methods: Between 1980 and 2009, 391 patients were diagnosed with aspergilloma at the Santa Casa Hospital Complex in Porto Alegre, Brazil. The diagnosis of aspergilloma in the pleural cavity was made through imaging tests revealing effusion and pleural thickening with air-fluid level; direct mycological examination revealing septate hyphae, consistent with Aspergillus sp.; and positive culture for A. fumigatus in the surgical specimen from the pleural cavity. Results: Of the 391 patients studied, 6 (2%) met the established diagnostic criteria. The mean age of those 6 patients was 48 years (range, 29-66 years), and 5 (83%) were male. The most common complaints were cough, expectoration, and hemoptysis. Four patients (67%) had a history of tuberculosis that had been clinically cured. All of the patients were submitted to surgical removal of the aspergilloma, followed ...
Hyperspectral imaging (HSI) is a technique based on the combination of classical spectroscopy and conventional digital image processing. It is also well suited for the biological assays and quantitative real-time analysis since it provides spectral and spatial data of samples. The method grants detailed information about a sample by recording the entire spectrum in each pixel of the whole image. We applied HSI to quantify the constituent pH variation in a single infected apoptotic monocyte as a model system. Previously, we showed that the human-pathogenic fungus Aspergillus fumigatus conidia interfere with the acidification of phagolysosomes. Here, we extended this finding to monocytes and gained a more detailed analysis of this process. Our data indicate that melanised A. fumigatus conidia have the ability to interfere with apoptosis in human monocytes as they enable the apoptotic cell to recover from mitochondrial acidification and to continue with the cell cycle. We also showed that this ability of A
Aspergillus fumigatus is a well-known opportunistic pathogen that causes invasive aspergillosis (IA) infections with high mortality in immunosuppressed individuals. Morphogenesis, including hyphal growth, conidiation, and cell wall biosynthesis is crucial in A. fumigatus pathogenesis. Based on a previous random insertional mutagenesis library, we identified the putative polysaccharide synthase gene Afcps1 and its para-log Afcps2. Homologs of the cps gene are commonly found in the genomes of most fungal and some bacterial pathogens. Afcps1/cpsA is important in sporulation, cell wall composition, and virulence. However, the precise regulation patterns of cell wall integrity by Afcps1/cpsA and further effects on the immune response are poorly understood. Specifically, our in-depth study revealed that Afcps1 affects cell-wall stability, showing an increased resistance of ΔAfcps1 to the chitinmicrofibril destabilizing compound calcofluor white (CFW) and susceptibility of ΔAfcps1 to the ...
could get genotypically -,,Jacques Meis: Yes.,,Christine Ginocchio: - with the resistance. Okay.,,Jacques Meis: At least in Europe. Im not sure what the epidemiology is here. Probably, you have also a lot of -,,Tom Chiller: We dont - we dont ...
Aspergillus fumigatus Basics Laboratory Metabolites Adverse health reactions Specific settings Diagnostic Bibliography Basics A. fumigatus has been associated with each and every type of health problems linked to environmental moulds: irritation and inflammation, allergy, asthma, pneumonitis, toxic effects as well as a wide range of infections. Infections have been reported
Fungal keratitis is a kind of intractable and sight-threatening diseases. Spleen-tyrosine kinase (Syk) is a non-receptor tyrosine kinase, which plays an important role in the signaling pathway of the receptors. In the current study, we investigate the expression and function of Syk in human corneal epithelial cells with Aspergillus fumigatus (A. fumigatus) infection. Cultured telomerase-immortalized human corneal epithelial cells (THCEs) were treated with A. fumigatus hyphae with or without treatment of Syk inhibitors. Activation of Syk and the role of Syk in regulating inflammatory cytokines and chemokines expression were evaluated. The mRNA expression was determined by real time PCR, and protein activation was measured by western blotting. Syk protein was detected in THCEs, and its activation was enhanced after treatment of A. fumigatus hyphae. Expression of inflammatory cytokines (IL-1β and IL-6) and chemokines (IL-8 and CXCL1) mRNA were significantly increased after stimulation of A. fumigatus
Due to the increase in the number of azole-resistant Aspergillus fumigatus, there is an urgent need of data to predict future trends and prevent further spreading. The intercountry transfer of resistant A. fumigatus on plant bulbs have been reported. We investigated existence and characteristics of resistant isolates attached to agricultural products imported to Japan. We purchased 292 samples in Japan. All samples were screened for the existence of azole-resistant A. fumigatus. For positive isolates, minimum inhibitory concentrations of the drugs were determined. We also analyzed Cyp51A, Hmg1, and Erg6 mutations of these isolates and conducted microsatellite genotyping. Fourteen azole-resistant isolates were detected, of which 13 were cultured from flower bulbs imported from the Netherlands. Among them 5 were from 11 bulbs of Hippeastrum (45.5%), 5 were from 24 bulbs of Gladiolus (20.8%), 2 were from 4 bulbs of Ixia (50.0%), and 1 was from 22 bulbs of Tulipa (4.5%). Only 1 resistant isolate was ...
The emergence of azole-resistant Aspergillus fumigatus has become a clinical problem in many parts of the world. Several amino acid mutations in the azole target protein Cyp51Ap contribute to this resistance, with the most concerning being the environmentally derived TR34 /L98H and TR46 /Y121F/T289A mutations. Here, we performed passive surveillance to assess a sample of the A. fumigatus population in the United States for the presence of these mutations. We found 1.4% of those isolates to exhibit elevated MIC via broth microdilution, and five of those isolates harbored the TR34 /L98H mutation ...
Review question We planned to review evidence about the effect of treatments to fight fungal infections which cause allergic bronchopulmonary aspergillosis in people with cystic fibrosis.. Background Allergic bronchopulmonary aspergillosis (ABPA) is an allergic lung reaction to a type of fungus (usually Aspergillus fumigatus) in some people with cystic fibrosis. It causes cough and wheezing and sometimes fever. If left untreated ABPA can lead to chronic lung damage. It is usually treated with a high dose of corticosteroids (also known as steroids). However, it has not been proven that corticosteroids can prevent lung function deteriorating in the long term. Also, long-term use of steroids is linked to some serious side effects. Treating the fungus which causes ABPA may be an alternative to using high doses of steroids to combat the allergic reaction. This is an update of a previously published review.. Search date The evidence is current to: 29 September 2016.. Study characteristics No trials ...
Allergic Bronchopulmonary Aspergillosis (ABPA): Symptoms ❗ Workup ❗ Diagnosis ❗ Treatment ❗ Complications ❗ Causes ❗ Epidemiology ❗ Incidence ❗ Prognosis ❗ Check at SYMPTOMA.com Allergic bronchopulmonary aspergillosis is a disease characterized by a hypersensitivity reaction to aspergillus fumigatus after its repeated inhalation and is most…
BioAssay record AID 322857 submitted by ChEMBL: Antifungal activity against azole-resistant Aspergillus fumigatus V34/75-CM3276 isolate from patient with hyper-immunoglobulin E syndrome by broth microdilution susceptibility test.
TY - JOUR. T1 - Damage to Aspergillus fumigatus and Rhizopus oryzae hyphae by oxidative and nonoxidative microbicidal products of human neutrophils in vitro. AU - Diamond, R. D.. AU - Clark, R. A.. PY - 1982. Y1 - 1982. N2 - Our previous studies established that human neutrophils could damage and probably kill hyphae of Aspergillus fumigatus and Rhizopus oryzae in vitro, primarily by oxygen-dependent mechanisms active at the cell surface. These studies were extended, again quantitating hyphal damage by reduction in uptake of 14C-labeled uracil or glutamine. Neither A. fumigatus nor R. oryzae hyphae were damaged by neutrophils from patients with chronic granulomatous disease, confirming the importance of oxidative mechanisms in damage to hyphae. In contrast, neutrophils from one patient with hereditary myeloperoxidase deficiency damaged R.C. oryzae but not A. fumigatus hyphae. Cell-free, in vitro systems were then used to help determine the relative importance of several potentially fungicidal ...
Caspofungin is a member of the echinocandin class of antifungal agents that inhibit the synthesis of β 1,3 glucan thus disrupting fungal cell wall structure and function. Exposure of the Aspergillus fumigatus cultures to caspofungin (0.01, 0.1 or 1.0 μ g/ml) resulted in a reduction in cell growth, but the production of the epipolythiodioxopiperazine toxin, gliotoxin, was comparable, or greater, in cultures exposed to caspofungin than untreated controls. Exposure of A. fumigatus hyphae to 1.0 μ g/ml caspofungin for 4 h resulted in the release of amino acids ( P 0.01), protein ( P 0.002) and gliotoxin ( P 0.02). Cultures of A. fumigatus incubated in the presence of caspofungin for 4 or 24 h demonstrated enhanced gliotoxin release ( P 0.04 and 0.03, respectively) and biosynthesis ( P 0.04 and 0.03, respectively) compared to that by control cultures. The results presented here indicate that exposure of A. fumigatus to caspofungin results in increased cell permeability and an increase in the ...
Allergic bronchopulmonary aspergillosis (ABPA) is a pulmonary disorder caused by a complex hypersensitivity response to antigens released by the fungus Aspergillus fumigatus. The management of ABPA includes two important aspects - institution of immunosuppressive therapy in the form of glucocorticoids to control the immunologic activity, and close monitoring for detection of relapses. Another possible target is to use antifungal agents to attenuate the fungal burden secondary to the fungal colonization in the airways. Oral corticosteroids are currently the treatment of choice for ABPA associated with bronchial asthma.They not only suppress the immune hyperfunction but are also anti-inflammatory. However, there is no data to guide the dose and duration of glucocorticoids and different regimens of glucocorticoids have been used in literature.Itraconazole, an oral triazole with relatively low toxicity, is active against Aspergillus spp. in vitro and in vivo. The activity of itraconazole against ...
TY - JOUR. T1 - Allergic bronchopulmonary aspergillosis treated successfully for one year with omalizumab. AU - Collins, Jennifer. AU - de Vos, Gabriele. AU - Hudes, Golda. AU - Rosenstreich, David. PY - 2012. Y1 - 2012. N2 - Background: Current therapy for allergic bronchopulmonary aspergillosis (ABPA) uses oral corticosteroids, exposing patients to the adverse effects of these agents. There are reports of the steroid-sparing effect of anti-IgE therapy with omalizumab for ABPA in patients with cystic fibrosis (CF), but there is little information on its efficacy against ABPA in patients with bronchial asthma without CF. Objective: To examine the effects of omalizumab, measured by asthma control, blood eosinophilia, total serum immunoglobulin E (IgE), oral corticosteroid requirements, and forced expiratory volume spirometry in patients with ABPA and bronchial asthma. Methods: A retrospective review of charts from 2004-2006 of patients treated with omalizumab at an academic allergy and immunology ...
This study describes a sudden death in an ostrich (Struthio camelus) with a big neck. Grossly, the air sacs were thickened. Yellow to white, round or coalescent material was scattered on the air sacs. However, the cervical air sac was normal. Histopathologically, multinucleated giant cells, heterophils, and macrophages had infiltrated the air sacs, and many hyphae were seen in the air sacs and on their surfaces. Pyogranulomatous inflammation with intralesional hyphae was observed throughout the lungs. Aspergillus fumigatus was identified microbiologically. In conclusion, the affected animal died because of the respiratory disturbance caused by mycotic airsacculitis and pneumonia.
Pseudomonas aeruginosa and Aspergillus fumigatus are common opportunistic bacterial and fungal pathogens, respectively. They often coexist in airways of immunocompromised patients and individuals with cystic fibrosis, where they form biofilms and cause acute and chronic illnesses. Hence, the interactions between them have long been of interest and it is known that P. aeruginosa can inhibit A. fumigatusin vitro We have approached the definition of the inhibitory P. aeruginosa molecules by studying 24 P. aeruginosa mutants with various virulence genes deleted for the ability to inhibit A. fumigatus biofilms. The ability of P. aeruginosa cells or their extracellular products produced during planktonic or biofilm growth to affect A. fumigatus biofilm metabolism or planktonic A. fumigatus growth was studied in agar and liquid assays using conidia or hyphae. Four mutants, the pvdD pchE, pvdD, lasR rhlR, and lasR mutants, were shown to be defective in various assays. This suggested the P. aeruginosa ...
Allergic bronchopulmonary aspergillosis (ABPA) is a condition characterised by an exaggerated response of the immune system (a hypersensitivity response) to the fungus Aspergillus (most commonly Aspergillus fumigatus). It occurs most often in patients with asthma or cystic fibrosis. Aspergillus spores are ubiquitous in soil and are commonly found in the sputum of healthy individuals. A. fumigatus is responsible for a spectrum of lung diseases known as aspergilloses. ABPA causes airway inflammation, leading to bronchiectasis-a condition marked by abnormal dilation of the airways. Left untreated, the immune system and fungal spores can damage sensitive lung tissues and lead to scarring. The exact criteria for the diagnosis of ABPA are not agreed upon. Chest X-rays and CT scans, raised blood levels of IgE and eosinophils, immunological tests for Aspergillus together with sputum staining and sputum cultures can be useful. Treatment consists of corticosteroids and antifungal medications. Almost all ...
Direct utilization of untreated oil palm trunk (OPT) for cellulases and xylanase production by Aspergillus fumigatus SK1 was conducted under solid-state fermentation (SSF). The highest activities of extracellular cellulases and xylanases were produced at 80% moisture level, initial pH 5.0, 1 × 108 spore/g (inoculum) with 125 μm of OPT as sole carbon source. The cellulases and xylanase activities obtained were 54.27, 3.36, 4.54 and 418.70 U/g substrates for endoglucanase (CMCase), exoglucanase (FPase), β-glucosidase and xylanase respectively. The crude cellulases and xylanase required acidic condition to retain their optimum activities (pH 4.0). Crude cellulases and xylanase were more stable at 40°C compared to their optimum activities conditions (60°C for FPase and 70°C for CMCase, β-glucosidase and xylanase). SDS-PAGE and zymogram analysis showed that Aspergillus fumigatus SK1 could secrete cellulases (endoglucanase, exoglucanase and β-glucosidase), xylanase and protease. Enzymatic ...
In vitro pharmacokinetic/pharmacodynamic data of liposomal amphotericin B (L-AMB) were compared with animal data from neutropenic and nonneutropenic models of azole-susceptible and azole-resistant invasive aspergillosis. L-AMB was equally effective. The in vitro fCmax (maximum concentration of free drug)/MIC ratio associated with 50% of maximal activity was 0.31 (0.29 to 0.33), similar to that in neutropenic but not nonneutropenic mice (0.11 [0.06 to 0.20]). Simulation analysis indicated that standard L-AMB doses (1 to 3 mg/kg) are adequate for nonneutropenic patients, but higher doses (7.5 to 10 mg/kg) may be required for neutropenic patients for Aspergillus fumigatus isolates with MICs of 0.5 to 1 mg/liter. ...
To gain insight into aberrant cytokine regulation in cystic fibrosis (CF), we compared the phenotypic manifestations of allergen challenge in gut-corrected CFTR-deficient mice with background-matched C57Bl6 (B6) mice. Aspergillus fumigatus (Af) antigen was used to mimic allergic bronchopulmonary aspergillosis, a peculiar hyper-IgE syndrome with a high prevalence in CF patients. CFTR-/-, C57BL/6 and FVB/NJ mice were sensitized with Af antigen by serial intraperitoneal injections. Control mice were mock sensitized with PBS. Challenges were performed by inhalation of Af antigen aerosol. After Af antigen challenge, histologic analysis showed goblet cell hyperplasia and lymphocytic infiltration in both strains. However, total serum IgE levels were markedly elevated in CF mice. Sensitized CF mice showed a five-fold greater IgE response to sensitization as compared with B6- and FVB-sensitized controls. Additional littermate controls to fully normalize for B6-FVB admixture in the strain background confirmed the
Invasive mycoses represent a major cause of morbidity and mortality in patients with malignancy or undergoing hematopoietic stem cell transplantation (HSCT). Recently it has been shown that the Toll-like receptor system could play an important role in the development of invasive aspergillosis in patients receiving chemotherapy or after HSCT, and there is evidence suggesting that the involvement of Toll-like receptors during Aspergillus fumigatus infection is influenced by the immunological status of the host. The upper and lower respiratory tracts represent the most frequent locations of A. fumigatus infection in all patient categories and age groups. Among echinocandins, caspofungin has been approved for salvage therapy in patients with invasive aspergillosis, since it has been demonstrated to be well-tolerated and with a 39% response in patients with refractory infections. However, in this study as in other salvage therapy trials, the need for salvage therapy was established in the presence of
This study investigated the dynamics of Aspergillus fumigatus azole-resistant phenotypes in two compost heaps with contrasting azole exposures: azole free and azole exposed. After heat shock, to which sexual but not asexual spores are highly resistant, the azole-free compost yielded 98% (49/50) wild-type and 2% (1/50) azole-resistant isolates, whereas the azole-containing compost yielded 9% (4/45) wild-type and 91% (41/45) resistant isolates. From the latter compost, 80% (36/45) of the isolates contained the TR46/Y121F/T289A genotype, 2% (1/45) harbored the TR46/Y121F/M172I/T289A/G448S genotype, and 9% (4/45) had a novel pan-triazole-resistant mutation (TR463/Y121F/M172I/T289A/G448S) with a triple 46-bp promoter repeat. Subsequent screening of a representative set of clinical A. fumigatus isolates showed that the novel TR463 mutant was already present in samples from three Dutch medical centers collected since 2012. Furthermore, a second new resistance mutation was found in this set that ...
An overview of Allergic Bronchopulmonary Aspergillosis (ABPA) symptoms, diagnosis, treatment & management written by experts in allergy, asthma & immunology.
Allergic bronchopulmonary aspergillosis (ABPA), a progressive fungal allergic lung disease, is a common complication of asthma or cystic fibrosis. Although ABPA has been recognized since the 1950s, recent research has underscored the importance of Th2 immune deviation and granulocyte activation in its pathogenesis. There is also strong evidence of widespread under-diagnosis due to the complexity and lack of standardization of diagnostic criteria. Treatment has long focused on downregulation of the inflammatory response with prolonged courses of oral glucocorticosteroids, but more recently concerns with steroid toxicity and availability of new treatment modalities has led to trials of oral azoles, inhaled amphotericin, pulse intravenous steroids, and subcutaneously-injected anti-IgE monoclonal antibody omalizumab, all of which show evidence of efficacy and reduced toxicity.
Chaudhary N, Staab JF, Marr KA. PLoS One 2010;5:e9036.. Aspergillus allergens are described as proteins that are recognized in patients with hypersensitivity syndromes such as allergic bronchopulmonary aspergillosis and Aspergillus-induced asthma. However, findings from this study indicate that (at least) some of these proteins are not only allergens, but are also capable of inducing a T-helper 1 (Th1) cytokine response in volunteers without a history of suspected or proven fungal infection or reported allergy or atopy. This indicates that these Asp f proteins are able to induce both protective (Th1) and non-protective (Th2) inflammation. Depending on the hosts status, Aspergillus fumigatus is able to cause several diseases ranging from allergic (e.g. Aspergillus-induced asthma and allergic bronchopulmonary aspergillosis) to invasive (e.g. pulmonary aspergillosis and disseminated disease). A fumigatus conidia enter the body via the air and, if they are not cleared by phagocytic cells, spores ...
Allergic Bronchopulmonary Aspergillosis - Learn about the causes, symptoms, diagnosis & treatment from the Merck Manuals - Medical Consumer Version.
A collection of disease information resources and questions answered by our Genetic and Rare Diseases Information Specialists for Allergic bronchopulmonary aspergillosis
TY - JOUR. T1 - Fatal mycotic encephalitis in a Northern bottlenose whale (Hyperoodon ampullatus) caused by Aspergillus fumigatus. AU - Foster, G. AU - Dagleish, Mark P. AU - Reid, RJ. AU - Barley, Jason. AU - Howie, F. PY - 2008/11/30. Y1 - 2008/11/30. M3 - Article. VL - 163. SP - 602. EP - 604. JO - Veterinary Record. JF - Veterinary Record. SN - 0042-4900. IS - 20. ER - ...
Overview: What every practitioner needs to know Are you sure your patient has allergic bronchopulmonary aspergillosis? What are the typical findings for this disease? Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity lung disease due to bronchial colonization by Aspergillus fumigatus that occurs in susceptible patients with asthma and cystic fibrosis (CF). ABPA affects approximately 1-2%…. ...
Overview: What every practitioner needs to know Are you sure your patient has allergic bronchopulmonary aspergillosis? What are the typical findings for this disease? Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity lung disease due to bronchial colonization by Aspergillus fumigatus that occurs in susceptible patients with asthma and cystic fibrosis (CF). ABPA affects approximately 1-2%…. ...
Al harboured the same genotype of multi-triazole resistant A. fumigatus, isolated on two different occasions which raises concern on the exposure of hospitalized patients to this resistant genotype. In this context it is pertinent to mention that previously multi-triazole resistant TR34/L98H A. KS 176 biological activity fumigatus isolates have been reported from patients attending the outpatient departments of VPCI who were never exposed to azoles [22]. In addition multi-triazole resistant A. fumigatus has also been isolated from admitted patients of VPCI. The presence of A. fumigatus resistant to medical triazoles poses a threat to immunocompromised patients as alternative therapy is limited. Snelders et al. reported that TR34/L98H isolates from clinical and environmental origins were cross resistant to five triazole DMIs fungicides, propiconazole, bromuconazole, tebuconazole, epoxiconazole and difenoconazole and thus supporting the hypothesis that exposure of A. fumigatus to azole fungicides ...
Minimal Diagnostic Criteria for ABPA-Central Bronchiectasis (ABPA-CB) Asthma Central bronchiectasis Immediate cutaneous reactivity to Aspergillus species or A. fumigatus Elevated total serum IgE (>417 kU/L) Elevated serum IgE-A.fumigatus and or IgG- A.fumigatus compared to sera from prick positive patients with asthma
Non-fumigatus Aspergillus species are the leading cause of Aspergillus infections in the tropical and subtropical regions of the world. In a prospective study between 2015 and 2016, a total of 150 bronchoalveolar (BAL) specimens was collected from patients suspected to pulmonary aspergillosis (PA) underlying immunodeficiencies in Mashhad, Northeastern Iran, located in the Middle East. All Aspergillus strains were phylogenetically identified at the species level by PCR-sequencing of partial β-tubulin gene. Overall, Aspergillus species were isolated from 20 specimens originating from 10 (50%) patients with cancer, 5 (25%) patients receiving corticosteroid therapy, 3 (15%) organ transplant recipients and 2 (10%) patients admitted to intensive care unit (ICU ...
To investigate azole resistance in clinical Aspergillus isolates, we conducted prospective multicenter international surveillance. A total of 3,788 Aspergillus isolates were screened in 22 centers from 19 countries. Azole-resistant A. fumigatus was more frequently found (3.2% prevalence) than previo …
Question - Have allergic aspergillosis. Would a flare up result in low blood oxygen level?. Ask a Doctor about diagnosis, treatment and medication for Allergic bronchopulmonary aspergillosis, Ask an OBGYN, Gynecologic Oncology
Many patients with cystic fibrosis (CF) cough up mucus or have throat cultures that grow a common fungus called Aspergillus. In patients with CF, aspergillus is not known to cause direct damage to the lungs, but some patients respond with an allergic reaction that causes them to wheeze, cough, or have difficulty breathing. This allergic reaction is called ABPA. Current treatment for ABPA includes high dose steroids and an anti-fungal medicine. Treatment with steroids may be problematic for some people due to its side effects on blood sugar levels and the bones. Steroids are medications that decrease inflammation, including prednisone, medrol, dexamethasone and others.. Ongoing research at UPMC on the study Mechanisms of Immune Tolerance in ABPA has studied people with CF and ABPA versus those patients with CF that just grow A. fumigatus (Af) in the sputum, but do not have ABPA. You may have participated in this study. This study has shown that people with CF with the fungus, Af, in their ...
Aspergillus fumigatus, an opportunistic pathogenic fungus, is the major reason for invasive aspergillosis and constitute also as an allergenic origin. Despite of the importance of the pathogenity of this fungus, only little is known about the background of its pathogenity. A. fumigatus produces a series of secondary metabolites which can be alone or together responsible for the pathogenity. For example, this fungus produces gliotoxin, an epipolythiodixopiperazine, which is in vitro characterised as a potent agent for cell death. For this reason it was speculated, that this mycotoxin might be involved in the pathogenesis of A. fumigatus. It is still necessary to know more about the genetic information and biosynthesis of further secondary metabolites, which might function as virulence factors. The biosynthetic gene cluster of gliotoxin has been identified in A. fumigatus. In the genome sequence of A. fumigatus Af293, an additional putative biosynthetic gene cluster containing three genes with ...
By Jennifer Doucet & Anushka Jayasuriya - June 23, 2017. Microbes, including bacteria and fungi, have many tools to evade a host cells defenses and antimicrobial therapies. One tool is the creation of protective barriers called biofilms, made of proteins, DNA, and sugar polymers, which spread across surfaces and impede immune system responses and antimicrobial treatments. In fact, biofilms can make microbes up to 1000 times more resistant to treatment. Despite their critical role in resistance to antimicrobials, there are no currently licensed therapies that target mature biofilms.. The bacteria Pseudomonas aeruginosa and the fungus Aspergillus fumigatus both form sugar-rich biofilms in host tissues during infection. They cause serious infections worldwide, especially in immunocompromised patients or those with chronic disease. Additionally, co-colonization by both P. aeruginosa and A. fumigatus has been observed in patients with lung disease such as cystic fibrosis.. As recently published in ...
The used ABPA treatment regimen restored forced expiratory volume in 1 second (FEV) values to pre-ABPA levels within three months (p
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Invasive aspergillosis is still a major fungal infection in immunocompromised patients. On the other hand, on time diagnosis of disease in the primary stages of infection is highly imperative for appropriate antifungal therapy and decreases the mortality rate in suspected groups (16). There are several approaches for detection and diagnosis of IA in clinical samples of patients. However, conventional methods, including direct examination and culture, are the gold standard to identify the causing agents, but there are some limitations, such as being time consuming, lack of proper sensitivity in early stages of the disease, as well as false negative results when the patients take the antifungal drugs (17).. Molecular diagnostic methods including real-time PCR as well as GM- EIA are more sensitive and specific and can approve an early IA diagnosis clinical outcome, when the other diagnostic methods are negative. Moreover, rapid results could be offered due to GM- EIA and real-time PCR assay ...
In recent years acquired azole resistance in Aspergillus fumigatus has been increasingly reported and a dominant mechanism of resistance (TR34/L98H) was found in clinical and environmental isolates. The aim of the present study was to investigate the prevalence of azole resistance in environmental A. fumigatus isolates collected in northern Italy. A. fumigatus grew from 29 of 47 soil samples analysed. Azole-resistant isolates were detected in 13% (6/47) of the soil samples and in 21% (6/29) of the soil samples containing A. fumigatus. High minimal inhibitory concentrations (MIC) of itraconazole (≥16 mg/L) and posaconazole (≥0.5 mg/L) were displayed by nine isolates from six different soil samples, namely apple orchard (1 sample), rose pot compost (2 samples), and cucurbit yields (3 samples). Seven isolates had a MIC=2 mg/L of voriconazole. Seven of nine itraconazole and posaconazole resistant isolates harboured the same TR34/L98H mutation of cyp51A. These findings, together with the occurrence of
Various saprotrophic microorganisms, especially filamentous fungi, can efficiently degrade lignocellulose that is one of the most abundant natural materials on earth. It consists of complex carbohydrates and aromatic polymers found in the plant cell wall and thus in plant debris. Aspergillus fumigatus Z5 was isolated from compost heaps and showed highly efficient plant biomass-degradation capability. The 29-million base-pair genome of Z5 was sequenced and 9540 protein-coding genes were predicted and annotated. Genome analysis revealed an impressive array of genes encoding cellulases, hemicellulases and pectinases involved in lignocellulosic biomass degradation. Transcriptional responses of A. fumigatus Z5 induced by sucrose, oat spelt xylan, Avicel PH-101 and rice straw were compared. There were 444, 1711 and 1386 significantly differently expressed genes in xylan, cellulose and rice straw, respectively, when compared to sucrose as a control condition. Combined analysis of the genomic and transcriptomic
Axel Brakhage. Director of the Leibniz-Institute for Natural Product Research and Infection Biology - Hans-Knoell-Institute (HKI). and. Professor and Chair of Microbiology / Molecular Biology. Friedrich-Schiller-University Jena. Department Molecular and Applied Microbiology. Research. Pathogenicity of Aspergillus fumigatus and secondary metabolism of Aspergillus nidulans. ...
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Prolonged myelosuppression following CD19-directed CAR T-cell transfusion represents an important, yet underreported, adverse event. The resulting neutropenia and multifactorial immunosuppression can facilitate severe infectious complications. We describe the clinical course of a 59-year-old patient with relapsed/refractory DLBCL who received Axicabtagene-Ciloleucel (Axi-cel). The patient developed ASTCT grade I CRS and grade IV ICANS, necessitating admission to the neurological ICU and prolonged application of high-dose corticosteroids and other immunosuppressive agents. Importantly, neutropenia was profound (ANC | 100/μl), G-CSF-refractory, and prolonged, lasting more than 50 days. The patient developed severe septic shock 3 weeks after CAR transfusion while receiving anti-fungal prophylaxis with micafungin. His clinical status stabilized with broad anti-infective treatment and intensive supportive measures. An autologous stem cell backup was employed on day 46 to support hematopoietic recovery.
Species: Bovine, equine, canine and cats. Specimen: Depends on site of infection, e.g. foetal stomach content in abortion cases, swabs from nasal infections, tissue biopsies.. Container: Sterile container with tissue, fluid, swab. Collection protocol: Depends on sample type may involve removal of cotyledons or tissue biopsy, aspiration of fluid, nasal swab.. Special handling/shipping requirements: Dry swab samples are stable at room temperature. Other samples are to be transported and stored chilled. Do not freeze samples.. General information about the disease: Can cause site-specific mycotic disease e.g. mycotic abortion in cattle, guttural pouch mycosis in horses, nasal infections in dogs and cats. Infection is acquired from environmental sources, generally inhalation or ingestion. It is an opportunistic pathogen depending on impaired, overwhelmed or by-passed host defences to permit hyphal invasion of the tissues. Comparison with other related tests: PCR provides rapid detection and specific ...
Chitinase inhibitors have chemotherapeutic potential as fungicides, pesticides, and antiasthmatics. Argifin, a natural product cyclopentapeptide, competitively inhibits family 18 chitinases in the nanomolar to micromolar range and shows extensive substrate mimicry