The characterization of a family of secreted aspartyl proteinases in Candida albicans.

摘要

The opportunistic fungus Candida albicans continues to be a major cause of morbidity and mortality in immunocompromised hosts. Little is known about the adaptive capabilities that enable this previously commensal organism to become pathogenic. This thesis is actually series of investigations designed to characterize at a molecular level first, the individual types of Candida isolates which infected a population of human immunodeficiency virus (HIV)-infected men; and second, a family of secreted aspartyl proteinases (Saps) which may function as putative virulence factors in C. albicans. The first study showed that although a large number of different C. albicans isolates exist in a population of immunocompromised patients, for the most part, each person maintains a unique strain throughout the course of their HIV-infection. Each isolate of C. albicans must therefore be capable of causing disease in the right environment. What fungal characteristics might enable this commensal to become a pathogen? The following studies focused on the identification and characterization of a family of putative virulence factors, the Saps. Secreted aspartyl proteinases have been identified in a number of Candida species which are pathogenic in humans. The C. albicans SAP 3 and SAP 4 genes were isolated and sequenced. Additionally, the patterns of expression of SAPs 1, 2 and 3 in the C. albicans strain WO-1 were correlated with different phenotypic switch states. This correlation is perhaps suggestive of differing functional roles for the various Saps. Sequencing of the flanking regions from the four alleles of SAP1 in two different strains of C. albicans identified some potential cis-acting transcriptional regulatory regions. Future studies will test the functionality of these regions using a mutant Aequorea victoria green fluorescent protein reporter system in an auxotrophic isolate of the phenotypic switching strain WO-1.