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 . 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. The microarray data revealed that 1249 genes were differentially expressed during growth at these two temperatures. According to our results, modified significantly the expression of genes related to metabolism to adapt to new conditions. The high percentages of genes that encoded hypothetical or unclassified proteins differentially expressed implied that many as yet unknown genes were involved in the establishment of infection. Furthermore, amongst the genes implicated in virulence upregulated at 37 °C on the microarray, we found those that encoded proteins mainly related to allergens (Asp F1, Asp F2 and MnSOD), gliotoxin biosynthesis (GliP and GliZ), nitrogen (NiiA and NiaD) or iron (HapX, SreA, SidD and SidC) metabolism. However, gene expression in iron and nitrogen metabolism might be influenced not only by heat shock, but also by the availability of nutrients in the medium, as shown by the addition of fresh medium.


Article metrics loading...

Loading full text...

Full text loading...



  1. Abad A., Fernández-Molina J. V., Bikandi J., Ramírez A., Margareto J., Sendino J., Hernando F. L., Pontón J., Garaizar J., Rementeria A.(2010). What makes Aspergillus fumigatus a successful pathogen? Genes and molecules involved in invasive aspergillosis. Rev Iberoam Micol 27, 155182. [View Article][PubMed] [Google Scholar]
  2. Anderson, M. & Denning, D. W. (2001).Aspergillus fumigatus isolate AF293 (NCPF 7367). http://www.aspergillus.org.uk/indexhome.htm?secure/sequence_info/./genomeetings/isolate.htm~main
  3. Araujo R., Rodrigues A. G.(2004). Variability of germinative potential among pathogenic species of Aspergillus. J Clin Microbiol 42, 43354337. [View Article][PubMed] [Google Scholar]
  4. Barhoom S., Sharon A.(2004). cAMP regulation of “pathogenic” and “saprophytic” fungal spore germination. Fungal Genet Biol 41, 317326. [View Article][PubMed] [Google Scholar]
  5. Bayram O., Braus G. H.(2012). Coordination of secondary metabolism and development in fungi: the velvet family of regulatory proteins. FEMS Microbiol Rev 36, 124. [View Article][PubMed] [Google Scholar]
  6. Beauvais A., Latgé J. P.(2001). Membrane and cell wall targets in Aspergillus fumigatus. Drug Resist Updat 4, 3849. [View Article][PubMed] [Google Scholar]
  7. Bhabhra R., Askew D. S.(2005). Thermotolerance and virulence of Aspergillus fumigatus: role of the fungal nucleolus. Med Mycol 43 (Suppl 1), 8793. [View Article][PubMed] [Google Scholar]
  8. Bok J. W., Chung D., Balajee S. A., Marr K. A., Andes D., Nielsen K. F., Frisvad J. C., Kirby K. A., Keller N. P.(2006). GliZ, a transcriptional regulator of gliotoxin biosynthesis, contributes to Aspergillus fumigatus virulence. Infect Immun 74, 67616768. [View Article][PubMed] [Google Scholar]
  9. Chaudhary N., Marr K. A.(2011). Impact of Aspergillus fumigatus in allergic airway diseases. Clin Transl Allergy 1, 4. [View Article][PubMed] [Google Scholar]
  10. da Silva Ferreira M. E., Malavazi I., Savoldi M., Brakhage A. A., Goldman M. H. S., Kim H. S., Nierman W. C., Goldman G. H.(2006). Transcriptome analysis of Aspergillus fumigatus exposed to voriconazole. Curr Genet 50, 3244. [View Article][PubMed] [Google Scholar]
  11. Dagenais T. R. T., Keller N. P.(2009). Pathogenesis of Aspergillus fumigatus in invasive aspergillosis. Clin Microbiol Rev 22, 447465. [View Article][PubMed] [Google Scholar]
  12. del Palacio A., Cuétara M. S., Pontón J.(2003). [Laboratory diagnosis of invasive aspergillosis]. Rev Iberoam Micol 20, 9098 (in Spanish).[PubMed] [Google Scholar]
  13. Dhingra S., Andes D., Calvo A. M.(2012). VeA regulates conidiation, gliotoxin production, and protease activity in the opportunistic human pathogen Aspergillus fumigatus. Eukaryot Cell 11, 15311543. [View Article][PubMed] [Google Scholar]
  14. Farnell E., Rousseau K., Thornton D. J., Bowyer P., Herrick S. E.(2012). Expression and secretion of Aspergillus fumigatus proteases are regulated in response to different protein substrates. Fungal Biol 116, 10031012. [View Article][PubMed] [Google Scholar]
  15. Fraczek M. G., Rashid R., Denson M., Denning D. W., Bowyer P.(2010). Aspergillus fumigatus allergen expression is coordinately regulated in response to hydrogen peroxide and cyclic AMP. Clin Mol Allergy 8, 15. [View Article][PubMed] [Google Scholar]
  16. Gravelat F. N., Doedt T., Chiang L. Y., Liu H., Filler S. G., Patterson T. F., Sheppard D. C.(2008). In vivo analysis of Aspergillus fumigatus developmental gene expression determined by real-time reverse transcription-PCR. Infect Immun 76, 36323639. [View Article][PubMed] [Google Scholar]
  17. Gsaller F., Hortschansky P., Beattie S. R., Klammer V., Tuppatsch K., Lechner B. E., Rietzschel N., Werner E. R., Vogan A. A.& other authors (2014). The Janus transcription factor HapX controls fungal adaptation to both iron starvation and iron excess. EMBO J 33, 22612276. [View Article][PubMed] [Google Scholar]
  18. Haas H.(2012). Iron – a key nexus in the virulence of Aspergillus fumigatus. Front Microbiol 3, 28. [View Article][PubMed] [Google Scholar]
  19. Harris S. D., Momany M.(2004). Polarity in filamentous fungi: moving beyond the yeast paradigm. Fungal Genet Biol 41, 391400. [View Article][PubMed] [Google Scholar]
  20. Krijgsheld P., Bleichrodt R., van Veluw G. J., Wang F., Müller W. H., Dijksterhuis J., Wösten H. A.(2013). Development in Aspergillus. Stud Mycol 74, 129. [View Article][PubMed] [Google Scholar]
  21. Krishnan K., Ren Z., Losada L., Nierman W. C., Lu L. J., Askew D. S.(2014). Polysome profiling reveals broad translatome remodeling during endoplasmic reticulum (ER) stress in the pathogenic fungus Aspergillus fumigatus. BMC Genomics 15, 159. [View Article][PubMed] [Google Scholar]
  22. Lamarre C., Sokol S., Debeaupuis J. P., Henry C., Lacroix C., Glaser P., Coppée J. Y., François J. M., Latgé J. P.(2008). Transcriptomic analysis of the exit from dormancy of Aspergillus fumigatus conidia. BMC Genomics 9, 417. [View Article][PubMed] [Google Scholar]
  23. Latgé J. P.(1999). Aspergillus fumigatus and aspergillosis. Clin Microbiol Rev 12, 310350.[PubMed] [Google Scholar]
  24. Low S. Y., Dannemiller K., Yao M., Yamamoto N., Peccia J.(2011). The allergenicity of Aspergillus fumigatus conidia is influenced by growth temperature. Fungal Biol 115, 625632. [View Article][PubMed] [Google Scholar]
  25. McDonagh A., Fedorova N. D., Crabtree J., Yu Y., Kim S., Chen D., Loss O., Cairns T., Goldman G.& other authors (2008). Sub-telomere directed gene expression during initiation of invasive aspergillosis. PLoS Pathog 4, e1000154. [View Article][PubMed] [Google Scholar]
  26. Medina I., Carbonell J., Pulido L., Madeira S. C., Goetz S., Conesa A., Tárraga J., Pascual-Montano A., Nogales-Cadenas R.& other authors (2010). Babelomics: an integrative platform for the analysis of transcriptomics, proteomics and genomic data with advanced functional profiling. Nucleic Acids Res 38 (Web Server issue), W210-W213. [View Article][PubMed] [Google Scholar]
  27. Morton C. O., Varga J. J., Hornbach A., Mezger M., Sennefelder H., Kneitz S., Kurzai O., Krappmann S., Einsele H.& other authors (2011). The temporal dynamics of differential gene expression in Aspergillus fumigatus interacting with human immature dendritic cells in vitro. PLoS One 6, e16016. [View Article][PubMed] [Google Scholar]
  28. Nierman W. C., Pain A., Anderson M. J., Wortman J. R., Kim H. S., Arroyo J., Berriman M., Abe K., Archer D. B.& other authors (2005). Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus. Nature 438, 11511156. [View Article][PubMed] [Google Scholar]
  29. O’Gorman C. M.(2011). Airborne Aspergillus fumigatus conidia: a risk of factor for aspergillosis. Fungal Biol Rev 25, 151157. [View Article] [Google Scholar]
  30. Oosthuizen J. L., Gomez P., Ruan J., Hackett T. L., Moore M. M., Knight D. A., Tebbutt S. J.(2011). Dual organism transcriptomics of airway epithelial cells interacting with conidia of Aspergillus fumigatus. PLoS One 6, e20527. [View Article][PubMed] [Google Scholar]
  31. Osherov N.(2007). The virulence of Aspergillus fumigatus. In New Insights in Medical Mycology, pp. 185212. Edited by Kavanagh K.. Dordrecht: Springer. [View Article] [Google Scholar]
  32. Park S. J., Mehrad B.(2009). Innate immunity to Aspergillus species. Clin Microbiol Rev 22, 535551. [View Article][PubMed] [Google Scholar]
  33. Power T., Ortoneda M., Morrissey J. P., Dobson A. D.(2006). Differential expression of genes involved in iron metabolism in Aspergillus fumigatus. Int Microbiol 9, 281287.[PubMed] [Google Scholar]
  34. Priebe S., Linde J., Albrecht D., Guthke R., Brakhage A. A.(2011). FungiFun: a web-based application for functional categorization of fungal genes and proteins. Fungal Genet Biol 48, 353358. [View Article][PubMed] [Google Scholar]
  35. Priebe S., Kreisel C., Horn F., Guthke R., Linde J.(2014). FungiFun2: a comprehensive online resource for systematic analysis of gene lists from fungal species. Bioinformatics doi:10.1093/bioinformatics/btu627 [Epub ahead of print]. [View Article][PubMed] [Google Scholar]
  36. Rementeria A., López-Molina N., Ludwig A., Vivanco A. B., Bikandi J., Pontón J., Garaizar J.(2005). [Genes and molecules involved in Aspergillus fumigatus virulence]. Rev Iberoam Micol 22, 123 (in Spanish). [View Article][PubMed] [Google Scholar]
  37. Scharf D. H., Heinekamp T., Remme N., Hortschansky P., Brakhage A. A., Hertweck C.(2012). Biosynthesis and function of gliotoxin in Aspergillus fumigatus. Appl Microbiol Biotechnol 93, 467472. [View Article][PubMed] [Google Scholar]
  38. Schrettl M., Bignell E., Kragl C., Sabiha Y., Loss O., Eisendle M., Wallner A., Arst H. N. Jr, Haynes K., Haas H.(2007). Distinct roles for intra- and extracellular siderophores during Aspergillus fumigatus infection. PLoS Pathog 3, e128. [View Article][PubMed] [Google Scholar]
  39. Schrettl M., Kim H. S., Eisendle M., Kragl C., Nierman W. C., Heinekamp T., Werner E. R., Jacobsen I., Illmer P.& other authors (2008). SreA-mediated iron regulation in Aspergillus fumigatus. Mol Microbiol 70, 2743. [View Article][PubMed] [Google Scholar]
  40. Schrettl M., Beckmann N., Varga J., Heinekamp T., Jacobsen I. D., Jöchl C., Moussa T. A., Wang S., Gsaller F.& other authors (2010). HapX-mediated adaption to iron starvation is crucial for virulence of Aspergillus fumigatus. PLoS Pathog 6, e1001124. [View Article][PubMed] [Google Scholar]
  41. Sugui J. A., Kim H. S., Zarember K. A., Chang Y. C., Gallin J. I., Nierman W. C., Kwon-Chung K. J.(2008). Genes differentially expressed in conidia and hyphae of Aspergillus fumigatus upon exposure to human neutrophils. PLoS One 3, e2655. [View Article][PubMed] [Google Scholar]
  42. Tekaia F., Latgé J. P.(2005). Aspergillus fumigatus: saprophyte or pathogen?Curr Opin Microbiol 8, 385392. [View Article][PubMed] [Google Scholar]
  43. van Leeuwen M. R., Krijgsheld P., Bleichrodt R., Menke H., Stam H., Stark J., Wösten H. A., Dijksterhuis J.(2013). Germination of conidia of Aspergillus niger is accompanied by major changes in RNA profiles. Stud Mycol 74, 5970. [View Article][PubMed] [Google Scholar]

Data & Media loading...


Supplementary Data

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error