title: Different consequences of ACE2 and SWI5 gene disruptions for virulence of pathogenic and nonpathogenic yeasts.
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.
authors.affiliation: Aberdeen Fungal Group, School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom.
authors.forename: Donna M
authors.initials: DM
authors.lastname: MacCallum
authors.forename: Helen
authors.initials: H
authors.lastname: Findon
authors.forename: Claire C
authors.initials: CC
authors.lastname: Kenny
authors.forename: Geraldine
authors.initials: G
authors.lastname: Butler
authors.forename: Ken
authors.initials: K
authors.lastname: Haynes
authors.forename: Frank C
authors.initials: FC
authors.lastname: Odds
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity*; D041221:Candida glabrata / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity*; D002177:Candidiasis / Q000276:immunology / Q000382:microbiology*; D018797:Cell Cycle Proteins / Q000235:genetics; D002688:Chitinases / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005656:Fungal Proteins / Q000235:genetics*; D017353:Gene Deletion; D051379:Mice; D008807:Mice, Inbred BALB C; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000472:pathogenicity*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014774:Virulence / Q000235:genetics
chemical_list: C505770:ACE2 protein, Candida glabrata; C066778:ACE2 protein, S cerevisiae; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C080218:SWI5 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D002688:Chitinases