Thioredoxin Reductase 1 Is a Highly Immunogenic Cell Surface Antigen in Paracoccidioides spp., Candida albicans, and Cryptococcus neoformans
Year: 2020
Type: article
Abstract: The increasing number of immunocompromised people has made invasive fungal infections more common. The antifungal armamentarium, in contrast, is limited to a few classes of drugs, with frequent toxicity and low efficacy pointing to the need for new agents. Antibodies are great candidates for novel antifungals, as their specificity can result in lower toxicity. Additionally, the immunomodulatory activity of antibodies could treat the underlying cause of many invasive mycoses, immune disfunction. In a previous comparative genomics study, we identified several potential targets for novel antifungals. Here we validate one of these targets, thioredoxin reductase (TRR1), to produce antibodies that could be useful therapeutic tools. Recombinant TRR1 proteins were produced by heterologous expression in Escherichia coli of genes encoding the proteins from Candida albicans, Cryptococcus neoformans and Paracoccidioides lutzii. These proteins were then used to immunize mice, followed by detection of serum antibodies against them by ELISA and western blot. A first set of experiments in which individual mice were immunized repeatedly with TRR1 from a single species showed that all three were highly immunogenic, inducing mostly IgG1 antibodies, and that antibodies produced against one species cross-reacted with the others. In a second experiment, individual mice were immunized three times, each with the protein from a different species. The high titers of antibodies confirmed the presence of antigenic epitopes that were conserved in fungi but absent in humans. Immunofluorescence with sera from these immunized mice detected the protein in the cytoplasm and on the cell surface of fungi from all three species. These results validate TRR1 as a good target for potentially broad-spectrum antifungal antibodies.
Source: Frontiers in Microbiology
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,950
Funders: Georgia Clinical and Translational Science Alliance, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Conselho Nacional de Desenvolvimento Científico e Tecnológico, National Institutes of Health, National Institute of Allergy and Infectious Diseases, National Center for Advancing Translational Sciences
Awards: G1288185563, G1413460417, G1571545756, G180476886, G1933508692, G2436179761, G3224512413, G393554289, G4066584169, Clinical and Translational Science Award, Clinical and Translational Science Award, G6857066734, G9000172406, G9000194839, Molecular Characterization of C. neoformans Antibodies
OpenAlex ID: W2999224854