Proteomic analysis of the Candida albicans secretome and its antigenic properties in the human host

Candida albicans is a common opportunistic fungal pathogen, which normally resides on mucosal surfaces of healthy individuals as a harmless commensal. However, in immunocompromised patients, it can lead to superficial infections and even disseminated candidemia. So far the diagnosis of Candida infections remains difficult. During infection, C. albicans undergoes a yeast-to-hypha transition and secretes numerous proteins for invasion of host tissues and modulation of host immune response. A combined 2D gel- and LC-MS/MS-based proteomic analysis of C. albicans yeast and hyphal secretomes lead to a comprehensive secretome map. Both C. albicans yeast and hyphal secretomes mainly consist of cell wall-associated proteins, proteins in response to environmental stimuli, secreted proteases, lipases and adhesins and carbohydrate metabolism-associated proteins. Enrichment of peptides from the culture supernatant of C. albicans hyphal cells revealed that Ece1p is the most abundant proteolytically processed extracellular protein. Ece1p turned out to be the first fungal cytolytic peptide toxin that is crucial for mucosal invasion. The immunoproteomic study, based on the screening of sera from candidemia patients and three control groups, revealed a core set of 20 immunodominant anti-C. albicans extracellular protein antibodies, seven of which represent potential diagnostic markers for candidemia. In particularly, the mechanism underlying the high cross-reactivity of C. albicans extracellular antigens was elucidated. As shown here, glycosylation of C. albicans extracellular proteins enhanced the immunogenicity of glycopeptide epitopes and also led to relatively unspecific binding of antibodies, resulting in cross-reactivity of C. albicans protein antigens.