Inactivation of transcription factor gene ACE2 in the fungal pathogen Candida glabrata results in hypervirulence

Mohammed Kamran, Ana Maria Calcagno, Helen Findon, Elaine Bignell, Michael D. Jones, Peter Warn, Philip Hopkins, David W. Denning, Geraldine Butler, Thomas Rogers, Fritz A. Mühlschlegel, Ken Haynes

    Research output: Contribution to journalArticlepeer-review


    During an infection, the coordinated orchestration of many factors by the invading organism is required for disease to be initiated and to progress. The elucidation of the processes involved is critical to the development of a clear understanding of host-pathogen interactions. For Candida species, the inactivation of many fungal attributes has been shown to result in attenuation. Here we demonstrate that the Candida glabrata homolog of the Saccharomyces cerevisiae transcription factor gene ACE2 encodes a function that mediates virulence in a novel way. Inactivation of C. glabrata ACE2 does not result in attenuation but, conversely, in a strain that is hypervirulent in a murine model of invasive candidiasis. C. glabrata ace2 null mutants cause systemic infections characterized by fungal escape from the vasculature, tissue penetration, proliferation in vivo, and considerable overstimulation of the proinflammatory arm of the innate immune response. Compared to the case with wild-type fungi, mortality occurs much earlier in mice infected with C. glabrata ace2 cells, and furthermore, 200-fold lower doses are required to induce uniformly fatal infections. These data demonstrate that C. glabrata ACE2 encodes a function that plays a critical role in mediating the host-Candida interaction. It is the first virulence-moderating gene to be described for a Candida species.
    Original languageEnglish
    Pages (from-to)546-552
    Number of pages6
    JournalEukaryotic Cell
    Issue number2
    Publication statusPublished - Apr 2004


    • Alleles
    • Animals
    • genetics: Candida glabrata
    • microbiology: Candidiasis
    • pharmacology: Chitinase
    • genetics: DNA-Binding Proteins
    • genetics: Fungal Proteins
    • Gene Silencing
    • analysis: Interferon Type II
    • analysis: Interleukin-6
    • pathology: Liver
    • pathology: Lung
    • Mice
    • Phenotype
    • Research Support, Non-U.S. Gov't
    • genetics: Saccharomyces cerevisiae Proteins
    • genetics: Transcription Factors
    • analysis: Tumor Necrosis Factor-alpha
    • Virulence


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