Antibody Binding Alters the Characteristics and Contents of Extracellular Vesicles Released by <named-content content-type="genus-species">Histoplasma capsulatum</named-content>

ABSTRACT Histoplasma capsulatum produces extracellular vesicles containing virulence-associated molecules capable of modulating host machinery, benefiting the pathogen. Treatment of H. capsulatum cells with monoclonal antibodies (MAbs) can change the outcome of infection in mice. We evaluated the si...

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Autores principales:	Ludmila Matos Baltazar, Ernesto S. Nakayasu, Tiago J. P. Sobreira, Hyungwon Choi, Arturo Casadevall, Leonardo Nimrichter, Joshua D. Nosanchuk
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	H. capsulatum Hsp60 monoclonal antibodies vesicles Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/7406d3044c0c49e9a1fe8d66d8c99c27
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spelling	oai:doaj.org-article:7406d3044c0c49e9a1fe8d66d8c99c272021-11-15T15:21:23ZAntibody Binding Alters the Characteristics and Contents of Extracellular Vesicles Released by <named-content content-type="genus-species">Histoplasma capsulatum</named-content>10.1128/mSphere.00085-152379-5042https://doaj.org/article/7406d3044c0c49e9a1fe8d66d8c99c272016-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00085-15https://doaj.org/toc/2379-5042ABSTRACT Histoplasma capsulatum produces extracellular vesicles containing virulence-associated molecules capable of modulating host machinery, benefiting the pathogen. Treatment of H. capsulatum cells with monoclonal antibodies (MAbs) can change the outcome of infection in mice. We evaluated the sizes, enzymatic contents, and proteomic profiles of the vesicles released by fungal cells treated with either protective MAb 6B7 (IgG1) or nonprotective MAb 7B6 (IgG2b), both of which bind H. capsulatum heat shock protein 60 (Hsp60). Our results showed that treatment with either MAb was associated with changes in size and vesicle loading. MAb treatments reduced vesicle phosphatase and catalase activities compared to those of vesicles from untreated controls. We identified 1,125 proteins in vesicles, and 250 of these manifested differences in abundance relative to that of proteins in vesicles isolated from yeast cells exposed to Hsp60-binding MAbs, indicating that surface binding of fungal cells by MAbs modified protein loading in the vesicles. The abundance of upregulated proteins in vesicles upon MAb 7B6 treatment was 44.8% of the protein quantities in vesicles from fungal cells treated with MAb 6B7. Analysis of orthologous proteins previously identified in vesicles from other fungi showed that different ascomycete fungi have similar proteins in their extracellular milieu, many of which are associated with virulence. Our results demonstrate that antibody binding can modulate fungal cell responses, resulting in differential loading of vesicles, which could alter fungal cell susceptibility to host defenses. This finding provides additional evidence that antibody binding modulates microbial physiology and suggests a new function for specific immunoglobulins through alterations of fungal secretion. IMPORTANCE Diverse fungal species release extracellular vesicles, indicating that this is a common pathway for the delivery of molecules to the extracellular space. However, there has been no study reporting the impact of antibody binding to the fungal cell on extracellular vesicle release. In the present work, we observed that treatment of H. capsulatum cells with Hsp60-binding MAbs significantly changed the size and cargo of extracellular vesicles, as well as the enzymatic activity of certain virulence factors, such as laccase and phosphatase. Furthermore, this finding demonstrates that antibody binding can directly impact protein loading in vesicles and fungal metabolism. Hence, this work presents a new role for antibodies in the modification of fungal physiology.Ludmila Matos BaltazarErnesto S. NakayasuTiago J. P. SobreiraHyungwon ChoiArturo CasadevallLeonardo NimrichterJoshua D. NosanchukAmerican Society for MicrobiologyarticleH. capsulatumHsp60monoclonal antibodiesvesiclesMicrobiologyQR1-502ENmSphere, Vol 1, Iss 2 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	H. capsulatum Hsp60 monoclonal antibodies vesicles Microbiology QR1-502
spellingShingle	H. capsulatum Hsp60 monoclonal antibodies vesicles Microbiology QR1-502 Ludmila Matos Baltazar Ernesto S. Nakayasu Tiago J. P. Sobreira Hyungwon Choi Arturo Casadevall Leonardo Nimrichter Joshua D. Nosanchuk Antibody Binding Alters the Characteristics and Contents of Extracellular Vesicles Released by <named-content content-type="genus-species">Histoplasma capsulatum</named-content>
description	ABSTRACT Histoplasma capsulatum produces extracellular vesicles containing virulence-associated molecules capable of modulating host machinery, benefiting the pathogen. Treatment of H. capsulatum cells with monoclonal antibodies (MAbs) can change the outcome of infection in mice. We evaluated the sizes, enzymatic contents, and proteomic profiles of the vesicles released by fungal cells treated with either protective MAb 6B7 (IgG1) or nonprotective MAb 7B6 (IgG2b), both of which bind H. capsulatum heat shock protein 60 (Hsp60). Our results showed that treatment with either MAb was associated with changes in size and vesicle loading. MAb treatments reduced vesicle phosphatase and catalase activities compared to those of vesicles from untreated controls. We identified 1,125 proteins in vesicles, and 250 of these manifested differences in abundance relative to that of proteins in vesicles isolated from yeast cells exposed to Hsp60-binding MAbs, indicating that surface binding of fungal cells by MAbs modified protein loading in the vesicles. The abundance of upregulated proteins in vesicles upon MAb 7B6 treatment was 44.8% of the protein quantities in vesicles from fungal cells treated with MAb 6B7. Analysis of orthologous proteins previously identified in vesicles from other fungi showed that different ascomycete fungi have similar proteins in their extracellular milieu, many of which are associated with virulence. Our results demonstrate that antibody binding can modulate fungal cell responses, resulting in differential loading of vesicles, which could alter fungal cell susceptibility to host defenses. This finding provides additional evidence that antibody binding modulates microbial physiology and suggests a new function for specific immunoglobulins through alterations of fungal secretion. IMPORTANCE Diverse fungal species release extracellular vesicles, indicating that this is a common pathway for the delivery of molecules to the extracellular space. However, there has been no study reporting the impact of antibody binding to the fungal cell on extracellular vesicle release. In the present work, we observed that treatment of H. capsulatum cells with Hsp60-binding MAbs significantly changed the size and cargo of extracellular vesicles, as well as the enzymatic activity of certain virulence factors, such as laccase and phosphatase. Furthermore, this finding demonstrates that antibody binding can directly impact protein loading in vesicles and fungal metabolism. Hence, this work presents a new role for antibodies in the modification of fungal physiology.
format	article
author	Ludmila Matos Baltazar Ernesto S. Nakayasu Tiago J. P. Sobreira Hyungwon Choi Arturo Casadevall Leonardo Nimrichter Joshua D. Nosanchuk
author_facet	Ludmila Matos Baltazar Ernesto S. Nakayasu Tiago J. P. Sobreira Hyungwon Choi Arturo Casadevall Leonardo Nimrichter Joshua D. Nosanchuk
author_sort	Ludmila Matos Baltazar
title	Antibody Binding Alters the Characteristics and Contents of Extracellular Vesicles Released by <named-content content-type="genus-species">Histoplasma capsulatum</named-content>
title_short	Antibody Binding Alters the Characteristics and Contents of Extracellular Vesicles Released by <named-content content-type="genus-species">Histoplasma capsulatum</named-content>
title_full	Antibody Binding Alters the Characteristics and Contents of Extracellular Vesicles Released by <named-content content-type="genus-species">Histoplasma capsulatum</named-content>
title_fullStr	Antibody Binding Alters the Characteristics and Contents of Extracellular Vesicles Released by <named-content content-type="genus-species">Histoplasma capsulatum</named-content>
title_full_unstemmed	Antibody Binding Alters the Characteristics and Contents of Extracellular Vesicles Released by <named-content content-type="genus-species">Histoplasma capsulatum</named-content>
title_sort	antibody binding alters the characteristics and contents of extracellular vesicles released by <named-content content-type="genus-species">histoplasma capsulatum</named-content>
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/7406d3044c0c49e9a1fe8d66d8c99c27
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Antibody Binding Alters the Characteristics and Contents of Extracellular Vesicles Released by <named-content content-type="genus-species">Histoplasma capsulatum</named-content>

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