Characterization of the antifungal functions of a WGA-Fc (IgG2a) fusion protein binding to cell wall chitin oligomers

Susie Coutinho Liedke, Daniel Zamith Miranda, Kamilla Xavier Gomes, Jorge Luis S. Gonçalves, Susana Frases, Joshua D. Nosanchuk, Marcio L. Rodrigues, Leonardo Nimrichter, José Mauro Peralta, Allan J. Guimarães

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish (US)
Article number12187
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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Wheat Germ Agglutinins
Chitin
Protein Binding
Cell Wall
Histoplasma
Mycoses
Cryptococcus neoformans
Candida albicans
Phagocytosis
Saccharomyces cerevisiae
Pneumonia
Therapeutics
Spleen
Macrophages
Monoclonal Antibodies
Lung
Antibodies
Liver
Growth

ASJC Scopus subject areas

  • General

Cite this

Characterization of the antifungal functions of a WGA-Fc (IgG2a) fusion protein binding to cell wall chitin oligomers. / Liedke, Susie Coutinho; Miranda, Daniel Zamith; Gomes, Kamilla Xavier; Gonçalves, Jorge Luis S.; Frases, Susana; Nosanchuk, Joshua D.; Rodrigues, Marcio L.; Nimrichter, Leonardo; Peralta, José Mauro; Guimarães, Allan J.

In: Scientific Reports, Vol. 7, No. 1, 12187, 01.12.2017.

Research output: Contribution to journalArticle

Liedke, SC, Miranda, DZ, Gomes, KX, Gonçalves, JLS, Frases, S, Nosanchuk, JD, Rodrigues, ML, Nimrichter, L, Peralta, JM & Guimarães, AJ 2017, 'Characterization of the antifungal functions of a WGA-Fc (IgG2a) fusion protein binding to cell wall chitin oligomers', Scientific Reports, vol. 7, no. 1, 12187. https://doi.org/10.1038/s41598-017-12540-y
Liedke, Susie Coutinho ; Miranda, Daniel Zamith ; Gomes, Kamilla Xavier ; Gonçalves, Jorge Luis S. ; Frases, Susana ; Nosanchuk, Joshua D. ; Rodrigues, Marcio L. ; Nimrichter, Leonardo ; Peralta, José Mauro ; Guimarães, Allan J. / Characterization of the antifungal functions of a WGA-Fc (IgG2a) fusion protein binding to cell wall chitin oligomers. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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