Characterization of a 5-azacytidine-induced developmental Aspergillus fumigatus variant

Virulence. 2010 May-Jun;1(3):164-73. doi: 10.4161/viru.1.3.11750.


The hypomethylating agent 5-azacytidine (5AC) is widely used in patients at risk of invasive mycoses. We sought to determine whether 5AC affects the developmental competence and virulence of Aspergillus fumigatus. Incubation of A. fumigatus strain 293 with 5AC induced high-frequency conversion to a fluffy-variant (Af293 (FL) ). The conidiation defect was bypassed by exposing Af293 (FL) to light during the initial 18 hours of growth on solid media. Transcriptional profiling revealed differential expression of multiple genes involved in G-protein signaling, including a putative G-protein coupled photoreceptor (opsin), suggesting that impaired signaling through a light-responsive pathway upstream of brlA is responsible for this phenotype. Af293 (FL) was fully virulent in fruit fly and murine models of invasive aspergillosis. Moreover, Af293 (FL) overexpressed aspergillopepsin F, had increased elastase activity and was more angioinvasive than the parental wild-type strain. The 5AC-induced A. fumigatus fluffy variant illustrates the potential effects of chemotherapeutic agents on the developmental and pathobiologic characteristics of opportunistic fungi.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimetabolites, Antineoplastic / pharmacology*
  • Aspergillus fumigatus / drug effects
  • Aspergillus fumigatus / genetics
  • Aspergillus fumigatus / growth & development*
  • Aspergillus fumigatus / pathogenicity*
  • Azacitidine / pharmacology*
  • Disease Models, Animal
  • Drosophila melanogaster / microbiology
  • Female
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Fungal
  • Genetic Variation*
  • Genotype
  • Invasive Pulmonary Aspergillosis / microbiology*
  • Light
  • Mice
  • Mice, Inbred BALB C
  • Mutation
  • Oligonucleotide Array Sequence Analysis
  • Phenotype
  • Signal Transduction / genetics
  • Virulence


  • Antimetabolites, Antineoplastic
  • Fungal Proteins
  • Azacitidine