In vivo and ex vivo comparative transcriptional profiling of invasive and non-invasive Candida albicans isolates identifies genes associated with tissue invasion

Authors

  • Sascha Thewes,

    1. Division Mycology, Robert-Koch Institute, Berlin, Germany.
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  • Marianne Kretschmar,

    1. Institute of Medical Microbiology and Hygiene, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Mannheim, Germany.
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  • Hyunsook Park,

    1. Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
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  • Martin Schaller,

    1. Department of Dermatology, Eberhard Karls University of Tübingen, Tübingen, Germany.
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  • Scott G. Filler,

    1. Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
    2. David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
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  • Bernhard Hube

    Corresponding author
    1. Division Mycology, Robert-Koch Institute, Berlin, Germany.
    2. Friedrich Schiller University Jena, Germany
    3. Department of Microbial Pathogenicity, Leibniz Institute for Natural Product Research and Infection Biology – Hans Knoell Institute Jena, Germany.
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E-mail bernhard.hube@hki-jena.de; Tel. +49 (0) 3641 65 6880; Fax +49 (0) 3641 65 6882.

Summary

The human pathogenic fungus Candida albicans can cause a wide range of infections and invade multiple organs. To identify C. albicans genes that are expressed during invasion of the liver, we used genome-wide transcriptional profiling in vivo and ex vivo. By analysing the different phases of intraperitoneal infection from attachment to tissue penetration in a time-course experiment and by comparing the profiles of an invasive with those of a non-invasive strain, we identified genes and transcriptional pattern which are associated with the invasion process. This includes genes involved in metabolism, stress, and nutrient uptake, as well as transcriptional programmes regulating morphology and environmental sensing. One of the genes identified as associated with liver invasion was DFG16, a gene crucial for pH-dependent hyphal formation, correct pH sensing, invasion at physiological pH and systemic infection.

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