SUMMARY: Secreted aspartic proteinases (Saps) contribute to the virulence of Candida albicans in systemic animal models of infection. Seven genes encoding Saps (SAM-SAP7) have been identified to date but evidence suggested the existence of additional SAP genes. The screening of a C. albicans iZEMBL3 genomic library for the presence of other SAP genes was undertaken. Two new genes, SAP8 and SAPS, were isolated. The N-terminal amino acid sequence deduced from SAP8 downstream of a Kex2plike cleavage site corresponds to the N-terminal amino acid sequence of the 41 kDa Sap isolated and characterized previously. SAP8 mRNA was expressed preferentially in yeasts at 25 "C after 6 and 9 h growth in BSA-containing medium. SAPS encodes an aspartic proteinase with a Kex2pllike cleavage site and contains a putative glycophosphatidylinositol-anchor signal at the C-terminus. Although the SAPS gene product has not yet been isolated from cultures of C. albicans, transcripts of SAPS were observed preferentially in later growth phases when SAP8 expression had decreased.
AshJ.,
DominguezM.,
BergeronJ.J.M.,
ThomasD.Y.,
BourbonnaisY.1995; The yeast proprotein convertase encoded by YAP3 is a glycophosphatidylinositol-anchored protein that localizes to the plasma membrane.. J Biol Chem 270:20847–20854
ChambersS.P.,
PriorS.E.,
BarstowD.A.,
MiltonN.P.1988; The pMTL nic−-cloning vectors. 1. Improved poly linker region to facilitate the use of sonicated DNA for nucleotide sequencing.. Gene 68:139–149
HubeB.,
MonodM.,
SchofieldA.,
BrownA.J.P.,
GowN.A.R.1994; Expression of seven members of the gene family encoding secretory aspartyl proteinases in Candida albicans.
. Mol Microbiol 14:87–99
HubeB.,
SanglardD.,
MonodM.,
BrownA.J.P.,
GowN.A.R.1997a; Extracellular proteolytic activity of Candida species. In Host-Fungus Interplay.
. Proceedings of the 5th Symposium on Topics in Mycology 1995 pp. 109–122 Edited by
Vanden BosscheH.,
StevensD. A.,
OddsF. C.
Bethesda, MD: National Foundation for Infectious Diseases;
HubeB.,
SanglardD.,
OddsF. C.,
HessD.,
MonodM.,
SchaferW.,
BrownA.J.P.,
GowN.A.R.1997b; Disruption of each of the aspartyl proteinase genes SAP1, SAP2, and SAP3 of Candida albicans attenuates virulence.. Infect lmmun 65:3529–3538
JuliusD.,
BrakeA.,
BlairL.,
KunisawaR.,
ThornerJ.1984; Isolation of the putative structural gene for the lysine-argininecleaving endopeptidase required for processing of yeast prepro-α- factor.. Cell 37:1075–1089
MorrowB.,
SrikanthaT.,
SoilD.R.1992; Transcription of the gene for a pepsinogen, PEP1, is regulated by white-opaque switching in Candida albicans.
. Mol Cell Biol 12:2997–3005
MorrowB.,
RamseyH.,
SoilD.R.1994; Regulation of phase- specific genes in the more general switching system of Candida albicans strain 3153A.. J Med Vet Mycol 32:287–294
TogniG.,
SanglardD.,
FalchettoR.,
MonodM.1991; Isolation and nucleotide sequence of the extracellular acid protease gene (ACP) from the yeast Candida tropicalis.
. FEBS Lett 286:181–185
de ViraghP.A.,
SanglardD.,
TogniG.,
FalchettoR.,
MonodM.1993; Cloning and sequencing of two Candida parapsilosis genes encoding acid proteases.. J Gen Microbiol 139:335–342
WhiteT.C.,
AgabianN.1995; Candida albicans secreted aspartyl proteinases: isoenzyme pattern is determined by cell type, and levels are determined by environmental factors.. J Bacteriol 177:5215–5221