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.

doi:10.3390/vaccines8020269

Remodeling of the Histoplasma Capsulatum Membrane Induced by Monoclonal Antibodies

Journal Article · Tue Jun 02 00:00:00 EDT 2020 · Vaccines

DOI:https://doi.org/10.3390/vaccines8020269· OSTI ID:1631468

Burnet, Meagan C.; Zamith-Miranda, Daniel; Heyman, Heino M.; Weitz, Karl K.; Bredeweg, Erin L.; ;

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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Sponsoring Organization:: USDOE

OSTI ID:: 1631468

Journal Information:: Vaccines, Journal Name: Vaccines Journal Issue: 2 Vol. 8; ISSN VBSABP; ISSN 2076-393X

Publisher:: MDPICopyright Statement

Country of Publication:: Switzerland

Language:: English

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