Physiologic expression of the Candida albicans pescadillo homolog is required for virulence in a murine model of hematogenously disseminated candidiasis

Priya Uppuluri, Ashok K. Chaturvedi, Niketa Jani, Read Pukkila-Worley, Carlos Monteagudo, Eleftherios Mylonakis, Julia R. Köhler, Jose L. Lopez Ribota

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Morphogenetic conversions contribute to the pathogenesis of Candida albicans invasive infections. Many studies to date have convincingly demonstrated a link between filamentation and virulence; however, relatively little is known regarding the role of the filament-to-yeast transition during the pathogenesis of invasive candidiasis. We previously identified the C. albicans pescadillo homolog (PES1) as essential during yeast growth and growth of lateral yeast on hyphae but not during hyphal growth. Furthermore, we demonstrated that PES1 is required for virulence in vivo in a Galleria mellonella larva model of candidiasis. Here, we have used a regulatable tetO-PES1/pes1 strain to assess the contribution of C. albicans PES1 to pathogenesis in the commonly used and clinically relevant murine model of hematogenously disseminated candidiasis. Our results indicate that a physiologically controlled level of PES1 expression is required for full virulence in this animal model, with virulence defects observed both when PES1 is overexpressed and and when it is depleted. The pathogenetic defect of cells depleted of PES1 is not due to a general growth defect, as demonstrated by the fact that PES1-depleted cells still kill Caenorhabditis elegans as efficiently as the wild type due to hyphal outgrowth through worm tissues. Our results suggest a critical role of lateral yeast growth in the ability of C. albicans to normally proliferate within tissues, as well as a pivotal role for Pes1 in the normal developmental cycle of C. albicans within the mammalian host during infection.

Original languageEnglish (US)
Pages (from-to)1552-1556
Number of pages5
JournalEukaryotic Cell
Volume11
Issue number12
DOIs
StatePublished - Dec 2012

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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