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Aspergillus fumigatus

Nikolaus Rieber, Roel P Gazendam, Alexandra F Freeman, Amy P Hsu, Amanda L Collar, Janyce A Sugui, Rebecca A Drummond, Chokechai Rongkavilit, Kevin Hoffman, Carolyn Henderson, Lily Clark, Markus Mezger, Muthulekha Swamydas, Maik Engeholm, Rebecca Schüle, Bettina Neumayer, Frank Ebel, Constantinos M Mikelis, Stefania Pittaluga, Vinod K Prasad, Anurag Singh, Joshua D Milner, Kelli W Williams, Jean K Lim, Kyung J Kwon-Chung, Steven M Holland, Dominik Hartl, Taco W Kuijpers, Michail S Lionakis
Invasive pulmonary aspergillosis is a life-threatening mycosis that only affects patients with immunosuppression, chemotherapy-induced neutropenia, transplantation, or congenital immunodeficiency. We studied the clinical, genetic, histological, and immunological features of 2 unrelated patients without known immunodeficiency who developed extrapulmonary invasive aspergillosis at the ages of 8 and 18. One patient died at age 12 with progressive intra-abdominal aspergillosis. The other patient had presented with intra-abdominal candidiasis at age 9, and developed central nervous system aspergillosis at age 18 and intra-abdominal aspergillosis at age 25...
October 20, 2016: JCI Insight
Rodney Lacret, Ignacio Pérez-Victoria, Daniel Oves-Costales, Mercedes de la Cruz, Elizabeth Domingo, Jesús Martín, Caridad Díaz, Francisca Vicente, Olga Genilloud, Fernando Reyes
A new napyradiomycin, MDN-0170 (1), was isolated from the culture broth of the marine-derived actinomycete strain CA-271078, together with three known related compounds identified as 4-dehydro-4a-dechloronapyradiomycin A1 (2), napyradiomycin A1 (3) and 3-chloro-6,8-dihydroxy-8-α-lapachone (4). The structure of the new compound was determined using a combination of spectroscopic techniques, including 1D and 2D NMR and electrospray-time of flight mass spectrometry (ESI-TOF MS). The relative configuration of compound 1, which contains two independent stereoclusters, has been established by molecular modelling in combination with nOe and coupling constant analyses...
October 18, 2016: Marine Drugs
Nicole Robbins, Gerard D Wright, Leah E Cowen
Invasive fungal infections are becoming an increasingly important cause of human mortality and morbidity, particularly for immunocompromised populations. The fungal pathogens Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus collectively contribute to over 1 million human deaths annually. Hence, the importance of safe and effective antifungal therapeutics for the practice of modern medicine has never been greater. Given that fungi are eukaryotes like their human host, the number of unique molecular targets that can be exploited for drug development remains limited...
October 2016: Microbiology Spectrum
Richard J Bennett, B Gillian Turgeon
This article provides an overview of sexual reproduction in the ascomycetes, a phylum of fungi that is named after the specialized sacs or "asci" that hold the sexual spores. They have therefore also been referred to as the Sac Fungi due to these characteristic structures that typically contain four to eight ascospores. Ascomycetes are morphologically diverse and include single-celled yeasts, filamentous fungi, and more complex cup fungi. The sexual cycles of many species, including those of the model yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe and the filamentous saprobes Neurospora crassa, Aspergillus nidulans, and Podospora anserina, have been examined in depth...
October 2016: Microbiology Spectrum
Adela Martin-Vicente, Javier Capilla, Josep Guarro
Clinical and experimental data have shown discrepancies on the efficacy of combinations between triazoles and echinocandins. In this study, anidulafungin plus posaconazole have shown efficacy against a murine systemic infection by three strains of Aspergillus fumigatus The combination increased mice survival and reduced burden in the kidneys over the corresponding monotherapies and voriconazole. Clearance of kidneys was observed in 62% to 100% of animals (strain dependant). We observed good in vitro- in vivo correlation when a cutoff < 1 was indicative of synergy...
October 19, 2016: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
Dmitry A Argunov, Vadim B Krylov, Nikolay E Nifantiev
A new pyranoside-into-furanoside (PIF) rearrangement of selectively protected galactopyranosides, followed by controlled O(5) → O(6) benzoate migration, gives either 5-OH or 6-OH products. It has been applied for the synthesis of four oligosaccharides related to the galactomannan from Aspergillus fumigatus. The assembly of target oligosaccharides containing both (1→5) and (1→6) linkages between galactofuranosyl residues was performed by applying terminal mannoside and digalactofuranoside blocks, forming a versatile approach toward fungal and bacterial carbohydrate antigens containing both 5-O- and 6-O-substituted galactofuranoside residues...
October 19, 2016: Organic Letters
Alejandra Itzel González-Ramírez, Adrián Ramírez-Granillo, María Gabriela Medina-Canales, Aída Verónica Rodríguez-Tovar, María Angeles Martínez-Rivera
BACKGROUND: Biofilms are a highly structured consortia of microorganisms that adhere to a substrate and are encased within an extracellular matrix (ECM) that is produced by the organisms themselves. Aspergillus fumigatus is a biotechnological fungus that has a medical and phytopathogenic significance, and its biofilm occurs in both natural and artificial environments; therefore, studies on the stages observed in biofilm formation are of great significance due to the limited knowledge that exists on this specific topic and because there are multiple applications that are being carried out...
October 18, 2016: BMC Microbiology
Yiping Xia, Guiqiu Zhao, Jing Lin, Cui Li, Lin Cong, Nan Jiang, Qiang Xu, Qian Wang
BACKGROUND: The objective of this study is to observe whether cyclosporine A (CsA) inhibits the expression of dectin-1 in human corneal epithelial cells infected with Aspergillus fumigatus (A. fumigatus) and to investigate the molecular mechanisms of the inhibition. METHODS: Immortalized human corneal epithelial cells (HCECs) were pretreated with 1,25(OH)2D3 and VDR inhibitor for 1 h, and then they were pretreated with CsA for 12h. After these pretreatments, the HCECs were stimulated with A...
2016: PloS One
Kevin J Sheridan, Beatrix Elisabeth Lechner, Grainne O' Keeffe, Markus A Keller, Ernst R Werner, Herbert Lindner, Gary W Jones, Hubertus Haas, Sean Doyle
Ergothioneine (EGT; 2-mercaptohistidine trimethylbetaine) is a trimethylated and sulphurised histidine derivative which exhibits antioxidant properties. Here we report that deletion of Aspergillus fumigatus egtA (AFUA_2G15650), which encodes a trimodular enzyme, abrogated EGT biosynthesis in this opportunistic pathogen. EGT biosynthetic deficiency in A. fumigatus significantly reduced resistance to elevated H2O2 and menadione, respectively, impaired gliotoxin production and resulted in attenuated conidiation...
October 17, 2016: Scientific Reports
Philippa Douglas, Sean F Tyrrel, Robert P Kinnersley, Michael Whelan, Philip J Longhurst, Anna L Hansell, Kerry Walsh, Simon J T Pollard, Gillian H Drew
Bioaerosols are released in elevated quantities from composting facilities and are associated with negative health effects, although dose-response relationships are unclear. Exposure levels are difficult to quantify as established sampling methods are costly, time-consuming and current data provide limited temporal and spatial information. Confidence in dispersion model outputs in this context would be advantageous to provide a more detailed exposure assessment. We present the calibration and validation of a recognised atmospheric dispersion model (ADMS) for bioaerosol exposure assessments...
September 26, 2016: International Journal of Hygiene and Environmental Health
Ritesh Agarwal, Inderpaul S Sehgal, Sahajal Dhooria, Ashutosh N Aggarwal
Allergic bronchopulmonary aspergillosis (ABPA) is a complex pulmonary disorder characterized by recurrent episodes of wheezing, fleeting pulmonary opacities and bronchiectasis. It is the most prevalent of the Aspergillus disorders with an estimated five million cases worldwide. Despite six decades of research, the pathogenesis, diagnosis and treatment of this condition remains controversial. The International Society for Human and Animal Mycology has formed a working group to resolve the controversies around this entity...
October 17, 2016: Expert Review of Respiratory Medicine
Andreas Schneider, Michael Blatzer, Wilfried Posch, Ralf Schubert, Cornelia Lass-Flörl, Stanislaw Schmidt, Thomas Lehrnbecher
Natural Killer (NK) cells are active against Aspergillus fumigatus, which in turn is able to impair the host defense. Unfortunately, little is known on the mutual interaction of NK cells and A. fumigatus. We coincubated human NK cells with A. fumigatus hyphae and assessed the gene expression and protein concentration of selected molecules. We found that A. fumigatus up-regulates the gene expression of pro-inflammatory molecules in NK cells, but inhibited the release of these molecules resulting in intracellular accumulation and limited extracellular availability...
October 12, 2016: Oncotarget
Lakkhana Kanhayuwa, Robert H A Coutts
Novel families of short interspersed nuclear element (SINE) sequences in the human pathogenic fungus Aspergillus fumigatus, clinical isolate Af293, were identified and categorised into tRNA-related and 5S rRNA-related SINEs. Eight predicted tRNA-related SINE families originating from different tRNAs, and nominated as AfuSINE2 sequences, contained target site duplications of short direct repeat sequences (4-14 bp) flanking the elements, an extended tRNA-unrelated region and typical features of RNA polymerase III promoter sequences...
2016: PloS One
Sara Mohebbi, Florian Erfurth, Philipp Hennersdorf, Axel A Brakhage, Hans Peter Saluz
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...
2016: PloS One
Annegret Wiedemann, Anja Spadinger, Axel Löwe, Allison Seeger, Frank Ebel
Treatment of invasive fungal infections often fails due to the limited number of therapeutic options. In this study, we have analyzed the impact of agents activating the High Osmolarity Glycerol (HOG) pathway on molds that cause infections in humans and livestock. We found that agents like fludioxonil and iprodione, have a clear anti-fungal activity against pathogenic Aspergillus, Lichtheimia, Rhizopus and Scedosporium species. Only A. terreus turned out to be resistant to fludioxonil, even though it is sensitive to iprodione and able to adapt to hyperosmotic conditions...
September 28, 2016: International Journal of Medical Microbiology: IJMM
Nicola L D Overton, David W Denning, Paul Bowyer, Angela Simpson
BACKGROUND: In patients with asthma, the fungus Aspergillus fumigatus can cause allergic bronchopulmonary aspergillosis (ABPA). Familial ABPA is reported, and some genetic factors have been associated with the disease, however, these are small studies (n ≤ 38) and do not explain all cases of ABPA. METHODS: We analysed SNPs in 95 ABPA patients, comparing frequencies to 152 atopic asthmatic and 279 healthy controls. Twenty two genes were selected from literature, and 195 tagging SNPs were analysed for genetic association with ABPA using logistic regression corrected for multiple testing...
2016: Allergy, Asthma, and Clinical Immunology
Daisuke Hagiwara, Akira Watanabe, Katsuhiko Kamei, Gustavo H Goldman
Invasive aspergillosis is a life-threatening mycosis caused by the pathogenic fungus Aspergillus. The predominant causal species is Aspergillus fumigatus, and azole drugs are the treatment of choice. Azole drugs approved for clinical use include itraconazole, voriconazole, posaconazole, and the recently added isavuconazole. However, epidemiological research has indicated that the prevalence of azole-resistant A. fumigatus isolates has increased significantly over the last decade. What is worse is that azole-resistant strains are likely to have emerged not only in response to long-term drug treatment but also because of exposure to azole fungicides in the environment...
2016: Frontiers in Microbiology
Lilian Pereira Silva, Patrícia Alves de Castro, Thaila Fernanda Dos Reis, Mario Henrique Paziani, Márcia Regina Von Zeska Kress, Diego M Riaño-Pachón, Daisuke Hagiwara, Laure N A Ries, Neil Andrew Brown, Gustavo H Goldman
Invasive aspergillosis is predominantly caused by Aspergillus fumigatus and adaptations to stresses experienced within the human host are a prerequisite for the survival and virulence strategies of the pathogen. The central signal transduction pathway operating during hyperosmotic stress is the High Osmolarity Glycerol mitogen-activated protein kinase (MAPK) cascade. A. fumigatus MpkC and SakA, orthologues of the Saccharomyces cerevisiae Hog1p, constitute the primary regulator of the hyperosmotic stress response...
October 5, 2016: Cellular Microbiology
Gloria Crespo, Víctor González-Menéndez, Mercedes de la Cruz, Jesús Martín, Bastien Cautain, Pilar Sánchez, Ignacio Pérez-Victoria, Francisca Vicente, Olga Genilloud, Fernando Reyes
During a high-throughput screening program focused on the discovery and characterization of new antifungal compounds, a total of 8320 extracts from Fundacion MEDINA's collection were screened against a panel of 6 fungal parasitic strains, namely Candida glabrata, Candida krusei, Candida parapsilosis, Candida tropicalis, Candida albicans, and Aspergillus fumigatus. A total of 127 extracts displayed antifungal properties and, after LC/MS dereplication, 10 were selected for further fractionation. Bioassay-guided fractionation from a 1-L fermentation of one of these extracts, belonging to the fungus Chaetopsina sp...
October 5, 2016: Planta Medica
Pierre-Régis Burgel, André Paugam, Dominique Hubert, Clémence Martin
Aspergillus fumigatus is the main fungus cultured in the airways of patients with cystic fibrosis (CF). Allergic bronchopulmonary aspergillosis occurs in ~10% of CF patients and is clearly associated with airway damage and lung function decline. The effects of A. fumigatus colonization in the absence of allergic bronchopulmonary aspergillosis are less well established. Retrospective clinical studies found associations of A. fumigatus-positive cultures with computed tomography scan abnormalities, greater risk of CF exacerbations and hospitalizations, and/or lung function decline...
2016: Infection and Drug Resistance
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