Elucidation of potentially virulent factors of Candida albicans during serum adaptation by using quantitative time-course proteomics.

Candida albicans is an opportunistic pathogen that causes fatal disease if the host immunity is compromised. The mortality rate of systemic candidiasis is very high; hence, there is a ceaseless demand for novel pharmaceuticals. In this study, quantitative time-course proteomics of C. albicans during adaptation to fetal bovine serum (FBS) is described. Survival in blood is essential for virulence of C. albicans, and a detailed analysis is required. We cultivated C. albicans in FBS for 0-180min, and determined quantitative time-course variations of 1024 proteins in the cultured cells by using a LC-MS/MS system with a long monolithic silica capillary column. Clustering analysis identified FBS-induced proteins associated with detoxification of oxidative species, high-affinity glucose transport, citrate cycle, oxidative phosphorylation, and iron acquisition. Furthermore, we identified possible virulence factors such as orf19.4914.1 (named Blood-induced peptide 1, Blp1). Heterologous expression of BLP1 in Saccharomyces cerevisiae shortened the lag phase and resulted in a pleiotropic stress-tolerance phenotype, indicating a possible role for quick adaptation to a stressful environment. While further experiments are necessary to prove virulence of the identified factors, systematic identification of candidate virulence proteins in this study will lead to profound understanding of virulence of C. albicans. BIOLOGICAL SIGNIFICANCE: This paper describes time-course proteomics of C. albicans during adaptation to serum, which is an essential process for fatal systemic candidiasis. Using a LC-MS/MS system with a monolithic silica capillary column, we have successfully characterized time-course variations of 1024 proteins. Among them, orf19.4914.1 (Blp1) was identified as a novel pleiotropic stress-tolerance peptide, which could have an important role for virulence of C. albicans.