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 ...
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 ...
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 ...
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 ...
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 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, ...
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.
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 ...
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
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
Strong clinical and experimental evidence links qualitative and quantitative neutrophil deficiencies to fatal infections caused by A. fumigatus. Yet the role of the neutrophil in mediating the protection observed in normal hosts remains largely unknown. Recent studies indicate neutrophils from CXCR2-/- mice are unable to migrate toward chemokine gradients of KC and MIP-2, rendering these animals susceptible to fatal aspergillosis. Mice with a mutation in the gene encoding for the gp91phox component of the NADPH oxidase lack the ability to generate the reactive oxygen metabolites used by phagocytes in killing microbial pathogens, and these mice are also susceptible to invasive pulmonary aspergillosis. In this investigation of the innate response to A. fumigatus, CXCR2-/- and gp91-/- mice were used to mimic the qualitative and quantitative neutrophil defects that are known to predispose to invasive pulmonary aspergillosis, the most lethal form of Aspergillus diseases. By comparing the nature of ...
TY - JOUR. T1 - Posttraumatic invasive Aspergillus fumigatus wound infection. AU - Gettleman, Lynn K.. AU - Shetty, Avinash K.. AU - Prober, Charles G.. PY - 1999/8/1. Y1 - 1999/8/1. UR - http://www.scopus.com/inward/record.url?scp=0032782329&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0032782329&partnerID=8YFLogxK. U2 - 10.1097/00006454-199908000-00026. DO - 10.1097/00006454-199908000-00026. M3 - Article. C2 - 10462356. AN - SCOPUS:0032782329. VL - 18. SP - 745. EP - 747. JO - Pediatric Infectious Disease Journal. JF - Pediatric Infectious Disease Journal. SN - 0891-3668. IS - 8. ER - ...
In most individuals, when benign antigens are inhaled, the lung responds with a tolerogenic immunological response [13-15]. However, in diseases such as ABPA, tolerance is lost or not established, and patients become sensitized to the inhaled fungal antigen Aspergillus fumigatus. We have previously shown that peripheral CD11c + DCs and TSLP-DCs from ABPA patients induce robust Th2 cytokine responses from autologous CD4+ T-cells in an OX40L-dependent manner [7]. In addition, in our CF cohort, vitamin D deficiency was associated with ABPA. In vitro treatment with 1,25-(OH)2 vitamin D3 reduced the robust Th2 response in patients with ABPA [7]. Based on data from our observational study, we initiated a clinical trial to assess the safety and the immunological effects of supplemental vitamin D3 (cholecalciferol) in patients with CF and ABPA.. This Phase I trial was implemented to test the safety and efficacy of vitamin D supplementation in CF patients with documented evidence of Af seinsitization. ...
Four patients who had recently received kidney transplants became infected with Aspergillus fumigatus while receiving immunosuppressive therapy. Three were shown to have invasive pulmonary mycotic disease, and one of these had documented dissemination. A fourth patient had respiratory symptoms and fever and was found to have mycelial forms consistent with A. fumigatus in his sputum, verified by cultures. All four were effectively treated with amphotericin B in low, widely spaced doses. Early diagnosis was apparently the key to successful management of the invasive Aspergillus fumigatus infection in these patients. Discovery of mycelial forms in fresh preparations of sputa or bronchial washings is a valuable clue to active infections. Securing tissue by biopsy is warranted in those patients who develop a pulmonary infiltrate or cavity that is not otherwise causally explained. ...
Aspergillus fumigatus is the major filamentous fungal pathogen in humans. Invasive aspergillosis has up to a 90% mortality rate in particular patient population...
TY - JOUR. T1 - A role for the unfolded protein response (UPR) in virulence and antifungal susceptibility in Aspergillus fumigatus. AU - Richie, Daryl L.. AU - Hartl, Lukas. AU - Aimanianda, Vishukumar. AU - Winters, Michael S.. AU - Fuller, Kevin K.. AU - Miley, Michael D.. AU - White, Stephanie. AU - McCarthy, Jason W.. AU - Latgé, Jean Paul. AU - Feldmesser, Marta. AU - Rhodes, Judith C.. AU - Askew, David S.. PY - 2009/1/1. Y1 - 2009/1/1. N2 - Filamentous fungi rely heavily on the secretory pathway, both for the delivery of cell wall components to the hyphal tip and the production and secretion of extracellular hydrolytic enzymes needed to support growth on polymeric substrates. Increased demand on the secretory system exerts stress on the endoplasmic reticulum (ER), which is countered by the activation of a coordinated stress response pathway termed the unfolded protein response (UPR). To determine the contribution of the UPR to the growth and virulence of the filamentous fungal pathogen ...
BioAssay record AID 768982 submitted by ChEMBL: Antifungal activity against Aspergillus fumigatus MTCC 3376 at 30 degC after 72 hrs by microbroth dilution technique.
Aspergillus fumigatus ATCC ® MYA-3626™ Designation: T33439 Application: Antifungal susceptibility testing Ref Ref Emerging infectious disease research Biomedical Research and Development Material Respiratory research Opportunistic pathogen research
BioAssay record AID 114336 submitted by ChEMBL: Effective dose against Aspergillus fumigatus MTU6001 strain after iv administration in murine.
Aspergillus fumigatus IgM/IgG Antibody Detection An indirect EIA is designed for the detection of anti-galactomannan IgM/IgG antibodies in human serum or plasma. The antibodies are used as the markers for IA. Serological Profile of Invasive...
Glycosylphosphatidylinositol (GPI) represents a mechanism for the attachment of proteins to the plasma membrane found in all eukaryotic cells. GPI biosynthesis has been mainly studied in parasites, yeast, and mammalian cells. Aspergillus fumigatus, a
Specific surveys of the air for Aspergillus fumigatus were carried out in rural and urban situations over a 2-year period. Overall, low concentrations of spores were recorded with a higher incidence during the winter months. Counts in the open air and in a hospital ward showed similar fluctuations …
Purpose: We investigated the expression and function of thymic stromal lymphopoietin (TSLP) in telomerase-immortalized human corneal epithelial cells (THCEs) and telomerase-immortalized human stroma fibroblasts (THSFs) challenged by A. fumigatus hyphae and its relationship with Toll-like receptors (TLR).. Methods: We stimulated THCEs and THSFs with TLR2 Ligand zymosan, TLR4 ligand lipopolysaccharide (LPS), human recombinant TSLP or A. fumigatus hyphae for various periods, with or without the inhibition of TLR2, TLR4 or TSLP using monoclonal antibody or small interfering RNA previously. The release and expression of TLR2, TLR4, TSLP, IL-4, IL-8, IL-13 and TNF-α were measured by means of ELISA, quantitative RT-PCR or western blot.. Results: It was demonstrated that enhanced expression of TSLP, IL-4 and IL-13 was associated with the treatment of A. fumigatus hyphae in human corneal cell lines. Stimulation of THCEs and THSFs with TLR2 Ligand zymosan or TLR4 ligand lipopolysaccharide (LPS) induced ...
A recent study from the University of Manchester has shown that human cell lines can be used to study lung colonisation by the fungus Aspergillus fumigatus. The work, published in Nature Communications, was partly funded by an NC3Rs Fellowship to Dr Sara Gago. Exposure to Aspergillus fumigatus in the environment is constant but the fungus is normally cleared from the lungs. Patients with asthma or an immune defect, however, can often have difficulty clearing the pathogen leading to aspergillosis. The team at the University of Manchester have discovered a genetic mutation in humans linked to increased loads of fungal spores in the lungs. Many laboratories use mouse models to study aspergillosis, which can be associated with welfare concerns as they involve the development of severe lung disease and mild-to-moderate respiratory distress. Human cell-based models can offer a more relevant alternative; for example, the mutation discovered in this study is in a gene for a transcription factor not found in
Aspergillus fumigatus is a ubiquitously distributed filamentous fungus that has emerged as one of the most serious life-threatening pathogens in immunocompromised patients. The mechanisms for its pathogenicity are poorly understood. Here, we analyzed the proteome of dormant A. fumigatus conidia as the fungal entity having the initial contact with the host. Applying two-dimensional polyacrylamide gel electrophoresis (2-D PAGE), we established a 2-D reference map of conidial proteins. By MALDI-TOF mass spectrometry, we identified a total number of 449 different proteins. We show that 57 proteins of our map are over-represented in resting conidia compared to mycelium. Enzymes involved in reactive oxygen intermediates (ROI) detoxification, pigment biosynthesis, and conidial rodlet layer formation were highly abundant in A. fumigatus spores and most probably account for their enormous stress resistance. Interestingly, pyruvate decarboxylase and alcohol dehydrogenase were detectable in dormant ...
Phagocytosis of a fungus spore. Coloured scanning electron micrograph (SEM) of a neutrophil (green) phagocytosing (engulfing and destroying) spores from the fungus Aspergillus fumigatus (yellow). Neutrophils are the most abundant white blood cell and are part of the bodys immune system. Aspergillus fumigatus is common in dust, soil, and on plants and plant products such as hay or grain. It can cause a number of different diseases in humans, including allergic disorder, respiratory infection and invasive disease. - Stock Image P266/0123
Guinea pigs (0.4-0.45 kg in weight) were obtained from the Animal Center of the College of Basic Sciences, Jilin University. The use of these animals adhered to the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. A strain of A. fumigatus (JLMR054) that was isolated from a patient with fungal endophthalmitis was donated by the Fungal Department of the College of Basic Sciences, Jilin University. Using a 30-gauge needle and a 1.0-mL plastic syringe, 0.02 mL Aspergillus suspension (1.0 × 106 CFU/mL) was injected directly into the vitreous cavity of 30 guinea pigs at the pars plana, approximately 1.5 mm posterior to the limbus. Voriconazole and liposomal Amp-B were supplied in powder form by Livzon Pharmaceutical Group, Inc. (Zhuhai, China) and New Pioneer, Inc. (Shanghai, China), respectively. The powder was suspended in 100% dimethylsulfoxide prior to use. The animals were randomly divided into three groups. Group A (control group) received an intravitreally administered ...
Invasive aspergillosis (IA), often caused by Aspergillus fumigatus, is an important cause of death of immunocompromised patients. Several DNA-extraction methods and PCR assays are available for detecting Aspergillus fumigatus DNA in bronchoalveolar lavage (BAL) samples of patients with invasive aspergillosis. These methods are often time consuming and emphasize the need to develop a clinical relevant rapid DNA isolation assay that gives reliable results in a short time. We have developed a new and rapid method which yields results within six hours.This was achieved by combining high-speed cell disruption using a mechanical extraction procedure (FastPrep), with a real-time PCR assay based on TaqMan technology.A newly designed Aspergillus-fumigatus-specific probe and Aspergillus-fumigatus-specific primers were established. This combination also produces quantitative results by comparing the results with a DNA serial dilution used in the real-time PCR. BAL fluids and other material from 204 ...
Summary In the human pathogenic mold Aspergillus fumigatus, sexual identity is determined by the mating‐type idiomorphs MAT1‐1 and MAT1‐2 residing at the MAT ...
Results] We were able to observe 3,622 genes modulated in at least one timepoint in the mutant when compared to the wild type strain (3,211 and 411 at 10 and 30 minutes, respectively). Decreased mRNA abundance in the ΔcrzA was seen for genes encoding calcium transporters, transcription factors and genes that could be directly or indirectly involved in calcium metabolism. Increased mRNA accumulation was observed for some genes encoding proteins involved in stress response. AfCrzA overexpression in A. fumigatus increases the expression of several of these genes. The deleted strain of one of these genes, AfRcnA, belonging to a class of endogenous calcineurin regulators, calcipressins, had more calcineurin activity after exposure to calcium and was less sensitive to menadione 30 μM, hydrogen peroxide 2.5 mM, EGTA 25 mM, and MnCl2 25 mM. We constructed deletion, overexpression, and GFP fusion protein for the closely related A. nidulans AnRcnA. GFP::RcnA was mostly detected along the germling, did ...