Microevolution during serial mouse passage demonstrates FRE3 as a virulence adaptation gene in Cryptococcus neoformans

Guowu Hu, Shu Hui Chen, Jin Qiu, John E. Bennett, Timothy G. Myers, Peter R. Williamson

Research output: Contribution to journalArticle

Abstract

Passage in mice of opportunistic pathogens such as Cryptococcus neoformans is known to increase virulence, but little is known about the molecular mechanisms involved in virulence adaptation. Serial mouse passage of nine environmental strains of serotype A C. neoformans identified two highly adapted virulent strains that showed a 4-fold reduction in time to death after four passages. Transcriptome sequencing expression studies demonstrated increased expression of a FRE3-encoded iron reductase in the two strains but not in a control strain that did not demonstrate increased virulence during mouse passage. FRE3 was shown to express an iron reductase activity and to play a role in iron-dependent growth of C. neoformans. Overexpression of FRE3 in the two original environmental strains increased growth in the macrophage cell line J774.16 and increased virulence. These data demonstrate a role for FRE3 in the virulence of C. neoformans and demonstrate how the increased expression of such a "virulence acquisition gene" during the environment-to-mammal transition, can optimize the virulence of environmental strains in mammalian hosts.

Original languageEnglish (US)
Article numbere00941-14
JournalmBio
Volume5
Issue number2
DOIs
StatePublished - Apr 1 2014
Externally publishedYes

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Serial Passage
Cryptococcus neoformans
Virulence
Genes
Growth
Transcriptome
Mammals
Iron
Macrophages
Cell Line

ASJC Scopus subject areas

  • Microbiology
  • Virology

Cite this

Hu, G., Chen, S. H., Qiu, J., Bennett, J. E., Myers, T. G., & Williamson, P. R. (2014). Microevolution during serial mouse passage demonstrates FRE3 as a virulence adaptation gene in Cryptococcus neoformans. mBio, 5(2), [e00941-14]. https://doi.org/10.1128/mBio.00941-14

Microevolution during serial mouse passage demonstrates FRE3 as a virulence adaptation gene in Cryptococcus neoformans. / Hu, Guowu; Chen, Shu Hui; Qiu, Jin; Bennett, John E.; Myers, Timothy G.; Williamson, Peter R.

In: mBio, Vol. 5, No. 2, e00941-14, 01.04.2014.

Research output: Contribution to journalArticle

Hu, Guowu ; Chen, Shu Hui ; Qiu, Jin ; Bennett, John E. ; Myers, Timothy G. ; Williamson, Peter R. / Microevolution during serial mouse passage demonstrates FRE3 as a virulence adaptation gene in Cryptococcus neoformans. In: mBio. 2014 ; Vol. 5, No. 2.
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