Structure and Biomedical Applications of Amyloid Oligomer Nanoparticles

Amyloid oligomers are nonfibrillar polypeptide aggregates linked to diseases, such as Alzheimer’s and Parkinson’s. Here we show that these aggregates possess a compact, quasi-crystalline architecture that presents significant nanoscale regularity. The amyloid oligomers are dynamic assemblies and are able to release their individual subunits. The small oligomeric size and spheroid shape confer diffusible characteristics, electrophoretic mobility, and the ability to enter hydrated gel matrices or cells. We finally showed that the amyloid oligomers can be labeled with both fluorescence agents and iron oxide nanoparticles and can target macrophage cells. Oligomer amyloids may provide a new biological nanomaterial for improved targeting, drug release, and medical imaging

Immunoproteomic Analysis of Antibody Responses to Extracellular Proteins of <i>Candida albicans</i> Revealing the Importance of Glycosylation for Antigen Recognition

During infection, the human pathogenic fungus <i>Candida albicans</i> 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 <i>C. albicans</i> 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 <i>C. albicans</i> extracellular proteins during the yeast-to-hypha transition, which led to a comprehensive <i>C. albicans</i> secretome map. The serological responses to <i>C. albicans</i> 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 <i>C. albicans</i> 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