The identification of gene duplication and the role of secreted aspartyl proteinase 1 in Candida parapsilosis virulence.
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.
Department of Microbiology, University of Szeged, Közép fasor, Szeged, Hungary.
Péter
P
Horváth
Joshua D
JD
Nosanchuk
Zsuzsanna
Z
Hamari
Csaba
C
Vágvölgyi
Attila
A
Gácser
D016282:Aspartic Acid Endopeptidases / Q000235:genetics* / Q000378:metabolism; D002175:Candida / Q000201:enzymology* / Q000235:genetics* / Q000472:pathogenicity; D002177:Candidiasis / Q000453:epidemiology; D002851:Chromatography, High Pressure Liquid; D020440:Gene Duplication; D015966:Gene Expression Regulation, Fungal; D056426:Genetic Loci; D006720:Homozygote; D054884:Host-Pathogen Interactions; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008264:Macrophages / Q000382:microbiology; D009154:Mutation; D010587:Phagocytosis; D014774:Virulence
D016282:Aspartic Acid Endopeptidases; C086390:SAP1 protein, Candida albicans