Immunoproteomic Analysis of Antibody Responses to Extracellular Proteins of Candida albicans Revealing the Importance of Glycosylation for Antigen Recognition.

Abstract:

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/MS-based 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.

SEEK ID: https://funginet.hki-jena.de/publications/144

PubMed ID: 27386892

Projects: C1

Journal: J Proteome Res

Citation: J Proteome Res. 2016 Aug 5;15(8):2394-406. doi: 10.1021/acs.jproteome.5b01065. Epub 2016 Jul 22.

Date Published: 5th Aug 2016

Authors: T. Luo, Thomas Krüger, U. Knupfer, Lydia Kasper, N. Wielsch, Bernhard Hube, A. Kortgen, Michael Bauer, E. J. Giamarellos-Bourboulis, G. Dimopoulos, Axel Brakhage, Olaf Kniemeyer

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