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Apical Secretory Glycoprotein Complex Contributes to Cell Attachment and Entry by Cryptosporidium parvum

Cryptosporidium parvum is an enteric pathogen that invades epithelial cells in the intestine, where it resides at the apical surface in a unique epicellular location. Compared with those of related apicomplexan parasites, the processes of host cell attachment and invasion by C. parvum are poorly und...

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Autores principales: Akey, Marianna E., Xu, Rui, Ravindran, Soumya, Funkhouser-Jones, Lisa, Sibley, L. David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9973360/
https://www.ncbi.nlm.nih.gov/pubmed/36722968
http://dx.doi.org/10.1128/mbio.03064-22
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author Akey, Marianna E.
Xu, Rui
Ravindran, Soumya
Funkhouser-Jones, Lisa
Sibley, L. David
author_facet Akey, Marianna E.
Xu, Rui
Ravindran, Soumya
Funkhouser-Jones, Lisa
Sibley, L. David
author_sort Akey, Marianna E.
collection PubMed
description Cryptosporidium parvum is an enteric pathogen that invades epithelial cells in the intestine, where it resides at the apical surface in a unique epicellular location. Compared with those of related apicomplexan parasites, the processes of host cell attachment and invasion by C. parvum are poorly understood. The streamlined C. parvum genome contains numerous mucin-like glycoproteins, several of which have previously been shown to mediate cell attachment, although the majority are unstudied. Here, we identified the antigens recognized by monoclonal antibody (MAb) 1A5, which stains the apical end of sporozoites and mature merozoites. Immunoprecipitation with MAb 1A5 followed by mass spectrometry identified a heterodimer comprised of paralogous proteins which are related to additional orthologs in the genome of C. parvum and related species. Paralogous glycoproteins recognized by MAb 1A5 heterodimerize as a complex displayed on the parasite surface, and they also interact with lectins that suggest that they contain mucin-like, O-linked oligosaccharides. Although the gene encoding one of the paralogs was readily disrupted by CRISPR/Cas9 gene editing, its partner, which contains a mucin-like domain related to GP900, was refractory to deletion. Combined with the ability of MAb 1A5 to partially neutralize host cell attachment by sporozoites, these findings define a new family of secretory glycoproteins that participate in cell invasion by Cryptosporidium spp.
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spelling pubmed-99733602023-03-01 Apical Secretory Glycoprotein Complex Contributes to Cell Attachment and Entry by Cryptosporidium parvum Akey, Marianna E. Xu, Rui Ravindran, Soumya Funkhouser-Jones, Lisa Sibley, L. David mBio Research Article Cryptosporidium parvum is an enteric pathogen that invades epithelial cells in the intestine, where it resides at the apical surface in a unique epicellular location. Compared with those of related apicomplexan parasites, the processes of host cell attachment and invasion by C. parvum are poorly understood. The streamlined C. parvum genome contains numerous mucin-like glycoproteins, several of which have previously been shown to mediate cell attachment, although the majority are unstudied. Here, we identified the antigens recognized by monoclonal antibody (MAb) 1A5, which stains the apical end of sporozoites and mature merozoites. Immunoprecipitation with MAb 1A5 followed by mass spectrometry identified a heterodimer comprised of paralogous proteins which are related to additional orthologs in the genome of C. parvum and related species. Paralogous glycoproteins recognized by MAb 1A5 heterodimerize as a complex displayed on the parasite surface, and they also interact with lectins that suggest that they contain mucin-like, O-linked oligosaccharides. Although the gene encoding one of the paralogs was readily disrupted by CRISPR/Cas9 gene editing, its partner, which contains a mucin-like domain related to GP900, was refractory to deletion. Combined with the ability of MAb 1A5 to partially neutralize host cell attachment by sporozoites, these findings define a new family of secretory glycoproteins that participate in cell invasion by Cryptosporidium spp. American Society for Microbiology 2023-02-01 /pmc/articles/PMC9973360/ /pubmed/36722968 http://dx.doi.org/10.1128/mbio.03064-22 Text en Copyright © 2023 Akey et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Akey, Marianna E.
Xu, Rui
Ravindran, Soumya
Funkhouser-Jones, Lisa
Sibley, L. David
Apical Secretory Glycoprotein Complex Contributes to Cell Attachment and Entry by Cryptosporidium parvum
title Apical Secretory Glycoprotein Complex Contributes to Cell Attachment and Entry by Cryptosporidium parvum
title_full Apical Secretory Glycoprotein Complex Contributes to Cell Attachment and Entry by Cryptosporidium parvum
title_fullStr Apical Secretory Glycoprotein Complex Contributes to Cell Attachment and Entry by Cryptosporidium parvum
title_full_unstemmed Apical Secretory Glycoprotein Complex Contributes to Cell Attachment and Entry by Cryptosporidium parvum
title_short Apical Secretory Glycoprotein Complex Contributes to Cell Attachment and Entry by Cryptosporidium parvum
title_sort apical secretory glycoprotein complex contributes to cell attachment and entry by cryptosporidium parvum
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9973360/
https://www.ncbi.nlm.nih.gov/pubmed/36722968
http://dx.doi.org/10.1128/mbio.03064-22
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