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Open AccessArticle

Remodeling of the Histoplasma Capsulatum Membrane Induced by Monoclonal Antibodies

Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA
Department of Microbiology and Immunology and Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA
Environmental and Molecular Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA
Authors to whom correspondence should be addressed.
These authors contributed equally to the work.
Vaccines 2020, 8(2), 269;
Received: 24 April 2020 / Revised: 27 May 2020 / Accepted: 31 May 2020 / Published: 2 June 2020
(This article belongs to the Section Pathogens-host Immune Interface)
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. View Full-Text
Keywords: Histoplasma capsulatum; antibody; lipids; metabolism; multi-omics Histoplasma capsulatum; antibody; lipids; metabolism; multi-omics
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Burnet, M.C.; Zamith-Miranda, D.; Heyman, H.M.; Weitz, K.K.; Bredeweg, E.L.; Nosanchuk, J.D.; Nakayasu, E.S. Remodeling of the Histoplasma Capsulatum Membrane Induced by Monoclonal Antibodies. Vaccines 2020, 8, 269.

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