Different Consequences of ACE2 and SWI5 Gene Disruptions for Virulence of Pathogenic and Nonpathogenic Yeasts
- 1 September 2006
- journal article
- Published by American Society for Microbiology in Infection and Immunity
- Vol. 74 (9), 5244-5248
- https://doi.org/10.1128/iai.00817-06
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.Keywords
This publication has 25 references indexed in Scilit:
- Proteomic changes associated with inactivation of theCandida glabrata ACE2 virulence-moderating geneProteomics, 2005
- Temporal events in the intravenous challenge model for experimental Candida albicans infections in female miceMycoses, 2005
- Candida orthopsilosis and Candida metapsilosis spp. nov. To Replace Candida parapsilosis Groups II and IIIJournal of Clinical Microbiology, 2005
- Ectopic Expression of URA3 Can Influence the Virulence Phenotypes and Proteome of Candida albicans but Can Be Overcome by Targeted Reintegration of URA3 at the RPS10 LocusEukaryotic Cell, 2004
- Genome evolution in yeastsNature, 2004
- Inactivation of Transcription Factor Gene ACE2 in the Fungal Pathogen Candida glabrata Results in HypervirulenceEukaryotic Cell, 2004
- The Saccharomyces cerevisiae Mob2p–Cbk1p kinase complex promotes polarized growth and acts with the mitotic exit network to facilitate daughter cell–specific localization of Ace2p transcription factorThe Journal of cell biology, 2002
- Yeast Cbk1 and Mob2 Activate Daughter-Specific Genetic Programs to Induce Asymmetric Cell FatesCell, 2001
- Serial Regulation of Transcriptional Regulators in the Yeast Cell CycleCell, 2001
- New heterologous modules for classical or PCR‐based gene disruptions in Saccharomyces cerevisiaeYeast, 1994