Author | Liedke, Susie Coutinho | |
Author | Miranda, Daniel Zamith | |
Author | Gomes, Kamilla Xavier | |
Author | Gonçalves, Jorge Luis S. | |
Author | Frases, Susana | |
Author | Nosanchuk, Joshua D. | |
Author | Rodrigues, Marcio L. | |
Author | Nimrichter, Leonardo | |
Author | Peralta, José Mauro | |
Author | Guimaraes, Allan J. | |
Access date | 2023-07-18T08:10:33Z | |
Available date | 2023-07-18T08:10:33Z | |
Document date | 2017 | |
Citation | LIEDKE, Susie Coutinho et al. Characterization of the antifungal functions of a WGA-Fc (IgG2a) fusion protein binding to cell wall chitin oligomers. Scientific Reports, v. 7, n. 1, p. 1-17, 12187, Sept. 2017. | en_US |
ISSN | 2045-2322 | en_US |
URI | https://www.arca.fiocruz.br/handle/icict/59647 | |
Language | eng | en_US |
Publisher | Nature Publishing Group | en_US |
Rights | open access | en_US |
MeSH | Animals | en_US |
MeSH | Antifungal Agents | en_US |
MeSH | CHO Cells | en_US |
MeSH | Cell Wall | en_US |
MeSH | Chitin | en_US |
MeSH | Cricetulus | en_US |
MeSH | Disease Models, Animal | en_US |
MeSH | Fungi | en_US |
MeSH | Humans | en_US |
MeSH | Hybridomas | en_US |
MeSH | Immunoconjugates | en_US |
MeSH | Immunoglobulin Fc Fragments | en_US |
MeSH | Immunoglobulin G | en_US |
MeSH | Invasive Fungal Infections | en_US |
MeSH | Mice, Inbred C57BL | en_US |
MeSH | Recombinant Fusion Proteins | en_US |
MeSH | Wheat Germ Agglutinins | en_US |
Title | Characterization of the antifungal functions of a WGA-Fc (IgG2a) fusion protein binding to cell wall chitin oligomers | en_US |
Type | Article | en_US |
DOI | 10.1038/S41598-017-12540-Y | |
Abstract | The majority of therapeutic strategies for mycosis require the protracted administration of antifungals, which can result in significant toxicities and have unacceptable failure rates. Hence, there is an urgent need for the development of improved therapeutic approaches, and monoclonal antibody-based drugs are potentially a powerful alternative to standard antifungals. To develop a broad antibody-like reagent against mycosis, wheat germ agglutinin (WGA) was linked to the effector Fc region of murine IgG2a. The resultant WGA-Fc displayed high affinity to purified chitin and bound efficiently to fungal cell walls, co-localizing with chitin, in patterns ranging from circular (Histoplasma capsulatum) to punctate (Cryptococcus neoformans) to labeling at the bud sites (Candida albicans and Saccharomyces cerevisiae). WGA-Fc directly inhibited fungal growth in standard cultures. WGA-Fc opsonization increased fungal phagocytosis, as well augmented the antifungal functions by macrophages. Prophylactic administration of WGA-Fc fully protected mice against H. capsulatum, correlating with a reduction in lung, spleen and liver fungal burdens. Administration of WGA-Fc also dramatically diminished pulmonary inflammation. Hence, the opsonic activity of WGA-Fc effectively modulates fungal cell recognition and promotes the elimination of fungal pathogens. Therefore, we propose WGA-Fc as a potential "pan-fungal" therapeutic that should be further developed for use against invasive mycoses. | en_US |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Prof. Paulo de Góes. Departamento de Imunologia. Rio de Janeiro, RJ, Brazil. | en_US |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Laboratório de Glicobiologia de Eucariotos. Rio de Janeiro, RJ, Brazil / Departments of Medicine and Microbiology and Immunology. Albert Einstein College of Medicine. Bronx, USA. | en_US |
Affilliation | Universidade Federal Fluminense. Instituto Biomédico. Departamento de Microbiologia e Parasitologia. Niterói, RJ, Brazil. | en_US |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Prof. Paulo de Góes. Departamento de Imunologia. Rio de Janeiro, RJ, Brazil. | en_US |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Ultraestrutura Celular Hertha Meyer. Rio de Janerio, RJ, Brazil. | en_US |
Affilliation | Departments of Medicine and Microbiology and Immunology. Albert Einstein College of Medicine. Bronx, USA. | en_US |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Prof. Paulo de Góes. Laboratório de Biologia Celular de Leveduras Patogênicas. Rio de Janeiro, RJ, Brazil / Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brazil. | en_US |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Laboratório de Glicobiologia de Eucariotos. Rio de Janeiro, RJ, Brazil. | en_US |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Prof. Paulo de Góes. Departamento de Imunologia. Rio de Janeiro, RJ, Brazil. | en_US |
Affilliation | Universidade Federal Fluminense. Instituto Biomédico. Departamento de Microbiologia e Parasitologia. Rio de Janeiro, RJ, Brazil. | en_US |
Affilliation | Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil. | en_US |
Subject | Wheat-germ lectin | en_US |
Subject | Cryptococcus-neoformans | en_US |
Subject | Monoclonal-antibody | en_US |
Subject | Histoplasma-capsulatum | en_US |
Subject | Passive-immunization | en_US |
Subject | Candida albicans | en_US |
Subject | Fungal | en_US |
e-ISSN | 2045-2322 | |