title: Comprehensive characterization of secreted aspartic proteases encoded by a virulence gene family in Candida albicans.
abstract: Candida albicans is a commensal organism, but causes life-threatening infections in immunocompromised patients. Certain factors such as yeast-hyphae transition and hydrolytic enzymes are suggested as virulence attributes of C. albicans. Among them, 10 types of secreted aspartic protease (SAP) genes have received particular attention as a major virulence gene family. However, their full functional repertoire, including its biochemical properties, remains to be elucidated. Hence, we purified all Sap isozymes using Pichia pastoris and comprehensively determined and compared their biochemical properties. While optimum pH of Sap7 was 6.5 and that of Sap8 was 2.5, presence of other Sap isozymes functioning within a broad range of optimum pH could allow C. albicans to survive and cause infections in various tissues. The substrate specificities of Sap isozymes were analysed by using FRETS-25Xaa libraries. Sap7 and Sap10 showed high substrate specificity, while other Sap isozymes had broad substrate specificities. Principal component analysis revealed that the 10 Sap isozymes were clustered into 3 distinct groups in terms of their substrate specificities. Interestingly, Sap4-6, which are coproduced in the hyphal form, were clustered as the same group, indicating that they may target similar host proteins. These results will lead to further understanding of C. albicans pathogenicity.
authors.affiliation: Japan Society for the Promotion of Science, Sakyo-ku, Kyoto 606-8502, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Aoki
authors.forename: Nao
authors.initials: N
authors.lastname: Kitahara
authors.forename: Natsuko
authors.initials: N
authors.lastname: Miura
authors.forename: Hironobu
authors.initials: H
authors.lastname: Morisaka
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Kouichi
authors.initials: K
authors.lastname: Kuroda
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Ueda
mesh_terms: D057055:Aspartic Acid Proteases / Q000235:genetics* / Q000378:metabolism; D002176:Candida albicans / Q000201:enzymology* / Q000472:pathogenicity; D013379:Substrate Specificity
chemical_list: D057055:Aspartic Acid Proteases