The identification of gene duplication and the role of secreted aspartyl proteinase 1 in Candida parapsilosis virulence

Péter Horváth, Joshua D. Nosanchuk, Zsuzsanna Hamari, Csaba Vágvölgyi, Attila Gácser

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

In this study, we analyzed the role of Candida parapsilosis-secreted aspartyl proteinase isoenzyme 1 (SAPP1) in virulence. The in silico analysis of SAPP1 sequence revealed a 2871 base pair-duplicated region (SAPP1a and SAPP1b) in the genome of C. parapsilosis. We generated homozygous ΔΔsapp1a, ΔΔsapp1b, and ΔΔsapp1a-ΔΔsapp1b mutants. Notably, Sapp1 production in an inducer medium was reduced by approximately 50% in the ΔΔsapp1a and ΔΔsapp1b mutants, but the other validated SAPP gene (SAPP2) was not affected. In contrast, Sapp2 production was increased in the ΔΔsapp1a-ΔΔsapp1b mutant relative to wild-type (WT) yeast. The ΔΔsapp1a-ΔΔsapp1b strain was hypersusceptible to human serum and was attenuated in its capacity to damage host-effector cells. The phagocytosis and killing of ΔΔsapp1a- ΔΔsapp1b yeasts by human peripheral blood mononuclear cells (PBMCs) and PBMC-derived macrophages (PBMC-DM) was significantly enhanced relative to WT. Phagolysosomal fusion in PBMC-DMs occurred more than twice as frequently with ingested ΔΔsapp1a-ΔΔsapp1b yeast cells compared with WT.

Original languageEnglish (US)
Pages (from-to)923-933
Number of pages11
JournalJournal of Infectious Diseases
Volume205
Issue number6
DOIs
StatePublished - Mar 15 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Fingerprint Dive into the research topics of 'The identification of gene duplication and the role of secreted aspartyl proteinase 1 in Candida parapsilosis virulence'. Together they form a unique fingerprint.

Cite this