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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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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. |
format | Online Article Text |
id | pubmed-7349930 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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