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Aspergillus fumigatus transcriptome

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
Ken Oda, Elaine Bignell, S Earl Kang, Michelle Momany
Aspergillus fumigatus is the most common airborne pathogen causing fatal mycoses in immunocompromised patients. During the first 8 hours of development A. fumigatus conidia break dormancy, expand isotopically, establish an axis of polarity, and begin to extend germ tubes in a polar manner. The transition from isotropic to polar growth is critical for tissue invasion and pathogenesis. In the current work, we used two-color microarrays to examine the A. fumigatus transcriptome during early development, focusing on the isotropic to polar switch...
September 24, 2016: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
Mun-Gu Jung, Sung Su Kim, Jae-Hyuk Yu, Kwang-Soo Shin
The G-protein-coupled receptor (GPCR) family represents the largest and most varied collection of membrane embedded proteins that are sensitized by ligand binding and interact with heterotrimeric G proteins. Despite their presumed critical roles in fungal biology, the functions of the GPCR family members in the opportunistic human pathogen Aspergillus fumigatus are largely unknown, as only two (GprC and GprD) of the 15 predicted GPCRs have been studied. Here, we characterize the gprK gene, which is predicted to encode a hybrid GPCR with both 7-transmembrane and regulator of G-protein signaling (RGS) domains...
2016: PloS One
Patrícia Alves de Castro, Thaila Fernanda Dos Reis, Stephen K Dolan, Adriana Oliveira Manfiolli, Neil Andrew Brown, Gary W Jones, Sean Doyle, Diego M Riaño-Pachón, Fábio Márcio Squina, Camila Caldana, Ashutosh Singh, Maurizio Del Poeta, Daisuke Hagiwara, Rafael Silva-Rocha, Gustavo H Goldman
The serine-threonine kinase TOR, the Target of Rapamycin, is an important regulator of nutrient, energy and stress signaling in eukaryotes. Sch9, a Ser/Thr kinase of AGC family (the cAMP-dependent PKA, cGMP- dependent protein kinase G and phospholipid-dependent protein kinase C family), is a substrate of TOR. Here, we characterized the fungal opportunistic pathogen Aspergillus fumigatus Sch9 homologue (SchA). The schA null mutant was sensitive to rapamycin, high concentrations of calcium, hyperosmotic stress and SchA was involved in iron metabolism...
November 2016: Molecular Microbiology
Daisuke Hagiwara, Hiroki Takahashi, Yoko Kusuya, Susumu Kawamoto, Katsuhiko Kamei, Tohru Gonoi
BACKGROUND: Fungal conidia are usually dormant unless the extracellular conditions are right for germination. Despite the importance of dormancy, little is known about the molecular mechanism underlying entry to, maintenance of, and exit from dormancy. To gain comprehensive and inter-species insights, transcriptome analyses were conducted across Aspergillus fumigatus, Aspergillus niger, and Aspergillus oryzae. RESULTS: We found transcripts of 687, 694, and 812 genes were enriched in the resting conidia compared with hyphae in A...
2016: BMC Genomics
Anand Shah, Shichina Kannambath, Susanne Herbst, Andrew Rogers, Simona Soresi, Martin Carby, Anna Reed, Serge Mostowy, Matthew C Fisher, Sunil Shaunak, Darius P Armstrong-James
RATIONALE: Pulmonary aspergillosis is a lethal mold infection in the immunocompromised host. Understanding initial control of infection and how this is altered in the immunocompromised host are key goals for comprehension of the pathogenesis of pulmonary aspergillosis. OBJECTIVES: To characterize the outcome of human macrophage infection with Aspergillus fumigatus and how this is altered in transplant recipients on calcineurin inhibitor immunosuppressants. METHODS: We defined the outcome of human macrophage infection with A...
November 1, 2016: American Journal of Respiratory and Critical Care Medicine
Mirjam Fliesser, Charles Oliver Morton, Michael Bonin, Frank Ebel, Kerstin Hünniger, Oliver Kurzai, Hermann Einsele, Jürgen Löffler
The mold Aspergillus fumigatus causes life-threatening infections in immunocompromised patients. Over the past decade, new findings in research have improved our understanding of A. fumigatus-host interactions, including the recent identification of myeloid-expressed hypoxia-inducible factor 1α (HIF-1α) as a relevant immune-modulating transcription factor and potential therapeutic target in anti-fungal defense. However, the function of HIF-1α signaling for human anti-A. fumigatus immunity is still poorly understood, including its role in dendritic cells (DCs), which are important regulators of anti-fungal immunity...
December 2015: International Journal of Medical Microbiology: IJMM
Robert Altwasser, Clara Baldin, Jakob Weber, Reinhard Guthke, Olaf Kniemeyer, Axel A Brakhage, Jörg Linde, Vito Valiante
Mitogen activated protein kinases (MAPKs) are highly conserved in eukaryotic organisms. In pathogenic fungi, their activities were assigned to different physiological functions including drug adaptation and resistance. Aspergillus fumigatus is a human pathogenic fungus, which causes life-threatening invasive infections. Therapeutic options against invasive mycoses are still limited. One of the clinically used drugs is caspofungin, which specifically targets the fungal cell wall biosynthesis. A systems biology approach, based on comprehensive transcriptome data sets and mathematical modeling, was employed to infer a regulatory network and identify key interactions during adaptation to caspofungin stress in A...
2015: PloS One
Anne Beauvais, Jean-Paul Latgé
In vivo, Aspergillus fumigatus grows as a typical biofilm with hyphae covered by an extracellular matrix (ECM) composed of polysaccharides, galactomannan, and galactosaminogalactan. α1,3 glucans and melanin are also constitutive of the ECM in aspergilloma but not in invasive aspergillosis. In vitro, two biofilm models were established to mimic the in vivo situation. The first model (model 1) uses submerged liquid conditions and is characterized by slow growth, while the second model (model 2) uses agar medium and aerial conditions and is characterized by rapid growth...
August 2015: Microbiology Spectrum
Christian W Remmele, Christian H Luther, Johannes Balkenhol, Thomas Dandekar, Tobias Müller, Marcus T Dittrich
Fungal microorganisms frequently lead to life-threatening infections. Within this group of pathogens, the commensal Candida albicans and the filamentous fungus Aspergillus fumigatus are by far the most important causes of invasive mycoses in Europe. A key capability for host invasion and immune response evasion are specific molecular interactions between the fungal pathogen and its human host. Experimentally validated knowledge about these crucial interactions is rare in literature and even specialized host-pathogen databases mainly focus on bacterial and viral interactions whereas information on fungi is still sparse...
2015: Frontiers in Microbiology
Fangyan Chen, Changjian Zhang, Xiaodong Jia, Shuo Wang, Jing Wang, Yong Chen, Jingya Zhao, Shuguang Tian, Xuelin Han, Li Han
Lung epithelial cells constitute the first defense line of host against the inhaled Aspergillus fumigatus; however, the transcriptional response of human alveolar type II epithelial cells was still unclear. Here we used RNA-Seq technology to assess the transcriptome profiles of A549 cells following direct interaction with conidia of A. fumigatus. The total number of identified genes was 19118. Compared with uninfected A549 cells, 459 genes were differentially expressed in cells co-incubated with conidia for 8 h, including 302 up-regulated genes and 157 down-regulated genes...
2015: PloS One
Youzhi Miao, Dongyang Liu, Guangqi Li, Pan Li, Yangchun Xu, Qirong Shen, Ruifu Zhang
BACKGROUND: 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. RESULTS: The 29-million base-pair genome of Z5 was sequenced and 9540 protein-coding genes were predicted and annotated...
June 16, 2015: BMC Genomics
Flávio V Loures, Marc Röhm, Chrono K Lee, Evelyn Santos, Jennifer P Wang, Charles A Specht, Vera L G Calich, Constantin F Urban, Stuart M Levitz
Plasmacytoid dendritic cells (pDCs) were initially considered as critical for innate immunity to viruses. However, our group has shown that pDCs bind to and inhibit the growth of Aspergillus fumigatus hyphae and that depletion of pDCs renders mice hypersusceptible to experimental aspergillosis. In this study, we examined pDC receptors contributing to hyphal recognition and downstream events in pDCs stimulated by A. fumigatus hyphae. Our data show that Dectin-2, but not Dectin-1, participates in A. fumigatus hyphal recognition, TNF-α and IFN-α release, and antifungal activity...
February 2015: PLoS Pathogens
Juliane Macheleidt, Kirstin Scherlach, Toni Neuwirth, Wolfgang Schmidt-Heck, Maria Straßburger, Joseph Spraker, Joshua A Baccile, Frank C Schroeder, Nancy P Keller, Christian Hertweck, Thorsten Heinekamp, Axel A Brakhage
Aspergillus fumigatus is an opportunistic human pathogenic fungus causing life-threatening infections in immunocompromised patients. Adaptation to different habitats and also virulence of the fungus depends on signal perception and transduction by modules such as the cyclic AMP-dependent protein kinase A (PKA) pathway. Here, by transcriptome analysis, 632 differentially regulated genes of this important signaling cascade were identified, including 23 putative transcriptional regulators. The highest upregulated transcription factor gene was located in a previously unknown secondary metabolite gene cluster, which we named fmp, encoding an incomplete non-ribosomal peptide synthetase, FmpE...
April 2015: Molecular Microbiology
Mónica Sueiro-Olivares, Jimena V Fernandez-Molina, Ana Abad-Diaz-de-Cerio, Eva Gorospe, Elisabeth Pascual, Xabier Guruceaga, Andoni Ramirez-Garcia, Javier Garaizar, Fernando L Hernando, Javier Margareto, Aitor Rementeria
Aspergillus fumigatus is considered to be the most prevalent airborne pathogenic fungus and can cause invasive diseases in immunocompromised patients. It is known that its virulence is multifactorial, although the mechanisms of pathogenicity remain unclear. With the aim of improving our understanding of these mechanisms, we designed a new expression microarray covering the entire genome of A. fumigatus. In this first study, we analysed the transcriptomes of this fungus at the first steps of germination after being grown at 24 and 37 °C...
March 2015: Microbiology
Daisuke Hagiwara, Satoshi Suzuki, Katsuhiko Kamei, Tohru Gonoi, Susumu Kawamoto
Aspergillus fumigatus is a life-threatening pathogenic fungus, whose conidium is the infectious agent of aspergillosis. To better understand the mechanism underlying the long-term viability of conidia, we characterized a bZip transcription factor, AtfA, with special reference to stress-tolerance in conidia. The atfA deletion mutant conidia showed significant sensitivity to high temperature and oxidative stress. The trehalose content that accumulated in conidia was reduced in the mutant conidia. Transcriptome analysis revealed that AtfA regulated several stress-protection-related genes such as catA, dprA, scf1, and conJ at the conidiation stage...
December 2014: Fungal Genetics and Biology: FG & B
(no author information available yet)
[This corrects the article DOI: 10.1371/journal.ppat.1004487.].
November 2014: PLoS Pathogens
Dawoon Chung, Bridget M Barker, Charles C Carey, Brittney Merriman, Ernst R Werner, Beatrix E Lechner, Sourabh Dhingra, Chao Cheng, Wenjie Xu, Sara J Blosser, Kengo Morohashi, Aurélien Mazurie, Thomas K Mitchell, Hubertus Haas, Aaron P Mitchell, Robert A Cramer
The Aspergillus fumigatus sterol regulatory element binding protein (SREBP) SrbA belongs to the basic Helix-Loop-Helix (bHLH) family of transcription factors and is crucial for antifungal drug resistance and virulence. The latter phenotype is especially striking, as loss of SrbA results in complete loss of virulence in murine models of invasive pulmonary aspergillosis (IPA). How fungal SREBPs mediate fungal virulence is unknown, though it has been suggested that lack of growth in hypoxic conditions accounts for the attenuated virulence...
November 2014: PLoS Pathogens
Margherita Bertuzzi, Markus Schrettl, Laura Alcazar-Fuoli, Timothy C Cairns, Alberto Muñoz, Louise A Walker, Susanne Herbst, Maryam Safari, Angela M Cheverton, Dan Chen, Hong Liu, Shinobu Saijo, Natalie D Fedorova, Darius Armstrong-James, Carol A Munro, Nick D Read, Scott G Filler, Eduardo A Espeso, William C Nierman, Hubertus Haas, Elaine M Bignell
Destruction of the pulmonary epithelium is a major feature of lung diseases caused by the mould pathogen Aspergillus fumigatus. Although it is widely postulated that tissue invasion is governed by fungal proteases, A. fumigatus mutants lacking individual or multiple enzymes remain fully invasive, suggesting a concomitant requirement for other pathogenic activities during host invasion. In this study we discovered, and exploited, a novel, tissue non-invasive, phenotype in A. fumigatus mutants lacking the pH-responsive transcription factor PacC...
October 2014: PLoS Pathogens
Grainne O'Keeffe, Stephen Hammel, Rebecca A Owens, Thomas M Keane, David A Fitzpatrick, Gary W Jones, Sean Doyle
BACKGROUND: Aspergillus fumigatus produces a number of secondary metabolites, one of which, gliotoxin, has been shown to exhibit anti-fungal activity. Thus, A. fumigatus must be able to protect itself against gliotoxin. Indeed one of the genes in the gliotoxin biosynthetic gene cluster in A. fumigatus, gliT, is required for self-protection against the toxin- however the global self-protection mechanism deployed is unclear. RNA-seq was employed to identify genes differentially regulated upon exposure to gliotoxin in A...
2014: BMC Genomics
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