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Schlagwörter:
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Zusammenfassung:
During infection, the human pathogenic fungus Candida albicans undergoes a yeast-to-hypha transition, secretes
numerous proteins for invasion of host tissues, and modulates
the host’s immune response. Little is known about the interplay
of C. albicans secreted proteins and the host adaptive immune
system. Here, we applied a combined 2D gel- and LC−MS/MSbased
approach for the characterization of C. albicans extracellular
proteins during the yeast-to-hypha transition, which led
to a comprehensive C. albicans secretome map. The serological
responses to C. albicans extracellular proteins were investigated
by a 2D-immunoblotting approach combined with MS for protein identification. On the basis of the screening of sera from
candidemia and three groups of noncandidemia patients, a core set of 19 immunodominant antibodies against secreted proteins
of C. albicans was identified, seven of which represent potential diagnostic markers for candidemia (Xog1, Lip4, Asc1, Met6,
Tsa1, Tpi1, and Prx1). Intriguingly, some secreted, strongly glycosylated protein antigens showed high cross-reactivity with sera
from noncandidemia control groups. Enzymatic deglycosylation of proteins secreted from hyphae significantly impaired sera
antibody recognition. Furthermore, deglycosylation of the recombinantly produced, secreted aspartyl protease Sap6 confirmed a
significant contribution of glycan epitopes to the recognition of Sap6 by antibodies in patient’s sera.