Different consequences of ACE2 and SWI5 gene disruptions for virulence of pathogenic and nonpathogenic yeasts

Donna Margaret MacCallum, Helen Findon, Claire C Kenny, Geraldine Butler, Ken Haynes, Frank Christopher Odds

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Mutants of Candida albicans, Candida glabrata, and Saccharomyces cerevisiae with disruptions in the ACE2 gene and C. glabrata and S. cerevisiae swi5 disruption mutants were tested for virulence in a murine challenge model of disseminated yeast infection. All mutants showed a clumping phenotype, but clumping was minimized in challenge inocula by inclusion of chitinase in the growth medium. In animals rendered temporarily neutropenic by cyclophosphamide treatment, the C. glabrata ace2 null mutant was confirmed as hypervirulent: it led to early terminal illness and kidney, brain, and lung fungal burdens substantially and significantly larger than those in controls. The C. glabrata swi5 null mutant did not lead to terminal illness but generated significantly larger brain and lung burdens than those in controls. The C. albicans ace2 null mutant was very slightly attenuated and the S. cerevisiae ace2 and swi5 null mutants were substantially attenuated relative to their parental control strains. The phenotype of aggressive hypervirulence, unique to disruption of the C. glabrata ACE2 gene among the strains tested, was not seen when the C. glabrata ace2 strain was tested in immunologically intact mice. The different effects seen with these mutants rule out the clumping phenotype as the explanation for hypervirulence in the C. glabrata ace2 mutant. The absence of C. glabrata ace2 hypervirulence in healthy mice may be a tool for definitive future study of host-parasite cross talk in microbial opportunism.
Original languageEnglish
Pages (from-to)5244-5248
Number of pages5
JournalInfection and Immunity
Volume74
Issue number9
DOIs
Publication statusPublished - 1 Sep 2006

Keywords

  • Animals
  • Candida albicans
  • Candida glabrata
  • Candidiasis
  • Cell Cycle Proteins
  • Chitinase
  • DNA-Binding Proteins
  • Female
  • Fungal Proteins
  • Gene Deletion
  • Mice
  • Mice, Inbred BALB C
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Virulence

Fingerprint Dive into the research topics of 'Different consequences of <em>ACE2 </em>and <em>SWI5</em> gene disruptions for virulence of pathogenic and nonpathogenic yeasts'. Together they form a unique fingerprint.

Cite this