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

Ronen Ben-Ami, John Varga, Russell E. Lewis, Gregory S. May, William C. Nierman, Dimitrios P. Kontoyiannis

Research output: Contribution to journalArticlepeer-review

Abstract

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 (Af293FL). The conidiation defect was bypassed by exposing Af293FL 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. Af293FL was fully virulent in fruit fly and murine models of invasive aspergillosis. Moreover, Af293FL over expressed 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.

Original languageEnglish
Pages (from-to)164-173
Number of pages10
JournalVirulence
Volume1
Issue number3
DOIs
StatePublished - 2010
Externally publishedYes

Keywords

  • Aspergillus
  • Azacytidine
  • Development
  • G-protein
  • Virulence

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