TY - JOUR
T1 - The identification of gene duplication and the role of secreted aspartyl proteinase 1 in Candida parapsilosis virulence
AU - Horváth, Péter
AU - Nosanchuk, Joshua D.
AU - Hamari, Zsuzsanna
AU - Vágvölgyi, Csaba
AU - Gácser, Attila
N1 - Funding Information:
Financial support. This work was supported by the Hungarian Scientific Research Fund (PD 73250 to A. G., NF 84006 to P. H. and A. G.), EMBO Installation Grant (1813 to A. G.), János Bolyai Research Scholarship of the Hungarian Academy of Sciences (to A. G. and Z. H.), and Irma T. Hirschl/Monique Weill-Caulier Trust Research Award (to J. D. N.).
PY - 2012/3/15
Y1 - 2012/3/15
N2 - 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.
AB - 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.
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U2 - 10.1093/infdis/jir873
DO - 10.1093/infdis/jir873
M3 - Article
C2 - 22301631
AN - SCOPUS:84857592978
SN - 0022-1899
VL - 205
SP - 923
EP - 933
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 6
ER -
