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Remodeling of the Histoplasma Capsulatum Membrane Induced by Monoclonal Antibodies

Antibodies play a central role in host immunity by directly inactivating or recognizing an invading pathogen to enhance different immune responses to combat the invader. However, the cellular responses of pathogens to the presence of antibodies are not well-characterized. Here, we used different mas...

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Autores principales: Burnet, Meagan C., Zamith-Miranda, Daniel, Heyman, Heino M., Weitz, Karl K., Bredeweg, Erin L., Nosanchuk, Joshua D., Nakayasu, Ernesto S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349930/
https://www.ncbi.nlm.nih.gov/pubmed/32498228
http://dx.doi.org/10.3390/vaccines8020269
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author Burnet, Meagan C.
Zamith-Miranda, Daniel
Heyman, Heino M.
Weitz, Karl K.
Bredeweg, Erin L.
Nosanchuk, Joshua D.
Nakayasu, Ernesto S.
author_facet Burnet, Meagan C.
Zamith-Miranda, Daniel
Heyman, Heino M.
Weitz, Karl K.
Bredeweg, Erin L.
Nosanchuk, Joshua D.
Nakayasu, Ernesto S.
author_sort Burnet, Meagan C.
collection PubMed
description Antibodies play a central role in host immunity by directly inactivating or recognizing an invading pathogen to enhance different immune responses to combat the invader. However, the cellular responses of pathogens to the presence of antibodies are not well-characterized. Here, we used different mass spectrometry techniques to study the cellular responses of the pathogenic fungus Histoplasma capsulatum to monoclonal antibodies (mAb) against HSP60, the surface protein involved in infection. A proteomic analysis of H. capsulatum yeast cells revealed that mAb binding regulates a variety of metabolic and signaling pathways, including fatty acid metabolism, sterol metabolism, MAPK signaling and ubiquitin-mediated proteolysis. The regulation of the fatty acid metabolism was accompanied by increases in the level of polyunsaturated fatty acids, which further augmented the degree of unsaturated lipids in H. capsulatum’s membranes and energy storage lipids, such as triacylglycerols, phosphatidylcholines, phosphatidylethanolamines and phosphatidylinositols. MAb treatment also regulated sterol metabolism by increasing the levels of cholesterol and ergosterol in the cells. We also showed that global changes in the lipid profiles resulted in an increased susceptibility of H. capsulatum to the ergosterol-targeting drug amphotericin B. Overall, our data showed that mAb induction of global changes in the composition of H. capsulatum membranes can potentially impact antifungal treatment during histoplasmosis.
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spelling pubmed-73499302020-07-15 Remodeling of the Histoplasma Capsulatum Membrane Induced by Monoclonal Antibodies Burnet, Meagan C. Zamith-Miranda, Daniel Heyman, Heino M. Weitz, Karl K. Bredeweg, Erin L. Nosanchuk, Joshua D. Nakayasu, Ernesto S. Vaccines (Basel) Article Antibodies play a central role in host immunity by directly inactivating or recognizing an invading pathogen to enhance different immune responses to combat the invader. However, the cellular responses of pathogens to the presence of antibodies are not well-characterized. Here, we used different mass spectrometry techniques to study the cellular responses of the pathogenic fungus Histoplasma capsulatum to monoclonal antibodies (mAb) against HSP60, the surface protein involved in infection. A proteomic analysis of H. capsulatum yeast cells revealed that mAb binding regulates a variety of metabolic and signaling pathways, including fatty acid metabolism, sterol metabolism, MAPK signaling and ubiquitin-mediated proteolysis. The regulation of the fatty acid metabolism was accompanied by increases in the level of polyunsaturated fatty acids, which further augmented the degree of unsaturated lipids in H. capsulatum’s membranes and energy storage lipids, such as triacylglycerols, phosphatidylcholines, phosphatidylethanolamines and phosphatidylinositols. MAb treatment also regulated sterol metabolism by increasing the levels of cholesterol and ergosterol in the cells. We also showed that global changes in the lipid profiles resulted in an increased susceptibility of H. capsulatum to the ergosterol-targeting drug amphotericin B. Overall, our data showed that mAb induction of global changes in the composition of H. capsulatum membranes can potentially impact antifungal treatment during histoplasmosis. MDPI 2020-06-02 /pmc/articles/PMC7349930/ /pubmed/32498228 http://dx.doi.org/10.3390/vaccines8020269 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Burnet, Meagan C.
Zamith-Miranda, Daniel
Heyman, Heino M.
Weitz, Karl K.
Bredeweg, Erin L.
Nosanchuk, Joshua D.
Nakayasu, Ernesto S.
Remodeling of the Histoplasma Capsulatum Membrane Induced by Monoclonal Antibodies
title Remodeling of the Histoplasma Capsulatum Membrane Induced by Monoclonal Antibodies
title_full Remodeling of the Histoplasma Capsulatum Membrane Induced by Monoclonal Antibodies
title_fullStr Remodeling of the Histoplasma Capsulatum Membrane Induced by Monoclonal Antibodies
title_full_unstemmed Remodeling of the Histoplasma Capsulatum Membrane Induced by Monoclonal Antibodies
title_short Remodeling of the Histoplasma Capsulatum Membrane Induced by Monoclonal Antibodies
title_sort remodeling of the histoplasma capsulatum membrane induced by monoclonal antibodies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349930/
https://www.ncbi.nlm.nih.gov/pubmed/32498228
http://dx.doi.org/10.3390/vaccines8020269
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