Candida albicans VPS4 is required for secretion of aspartyl proteases and in vivo virulence

Samuel A. Lee, Jason Jones, Sarah Hardison, John Kot, Zachary Khalique, Stella M. Bernardo, Anna Lazzell, Carlos Monteagudo, Jose Lopez-Ribot

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18 Citations (Scopus)

Abstract

Candida albicans secretes aspartyl proteases (Saps) during infection. Although Saps are secretory proteins, little is known about the intracellular trafficking and secretion of these proteins. We previously cloned and analyzed the C. albicans pre-vacuolar protein sorting gene VPS4, and demonstrated that extracellular Sap2p is absent in the culture supernatants of the vps4Δ null mutant. We therefore investigated the role of the C. albicans pre-vacuolar secretion pathway in the trafficking of Sap4-6p and in vivo virulence. The C. albicans vps4Δ mutant failed to produce extracellular Sap4-6p. Next, when tested in a mouse model of disseminated candidiasis, the vps4Δ mutant was greatly attenuated in virulence. Histopathological analysis indicated that infection with the vps4Δ mutant did not cause renal microabscess formation, in contrast to the wild-type strain. Our results imply that VPS4 is required for extracellular secretion of Sap4-6p, and that C. albicans requires an intact pre-vacuolar secretory pathway for wild-type virulence in vivo.

Original languageEnglish
Pages (from-to)55-63
Number of pages9
JournalMycopathologia
Volume167
Issue number2
Early online date24 Sep 2008
DOIs
Publication statusPublished - 1 Feb 2009

Keywords

  • Candida albicans
  • protein secretion
  • secreted aspartyl proteases
  • vacuole
  • virulence
  • VPS4

ASJC Scopus subject areas

  • Plant Science
  • Agronomy and Crop Science
  • Applied Microbiology and Biotechnology
  • Microbiology
  • veterinary (miscalleneous)

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    Lee, S. A., Jones, J., Hardison, S., Kot, J., Khalique, Z., Bernardo, S. M., Lazzell, A., Monteagudo, C., & Lopez-Ribot, J. (2009). Candida albicans VPS4 is required for secretion of aspartyl proteases and in vivo virulence. Mycopathologia, 167(2), 55-63. https://doi.org/10.1007/s11046-008-9155-7