<i>Cryptosporidium</i> secreted proteins form a complex layered interface with the host cell

Article Article scientifique Article <i>Cryptosporidium</i> secreted proteins form a complex layered interface with the host cell eng 2026-05-14 2026-05 author Puthenpurackal Annet Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 410126 Département de microbiologie et médecine moléculaire (MIMOL) author Moreno Sanchez Sandra Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 429727 Département de microbiologie et médecine moléculaire (MIMOL) author Schaer Tifany Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 740855 Département de microbiologie et médecine moléculaire (MIMOL) author Falconnet Léna Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 898001 Département de médecine (DEMED) author Niu Chengyue 0000-0001-8607-3419 Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 805693 author Vadas Oscar 0000-0003-3511-6479 Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 508966 Département de microbiologie et médecine moléculaire (MIMOL) author Guérin Amandine 0000-0001-8307-5099 Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 410740 Département de microbiologie et médecine moléculaire (MIMOL) e1014212 10.1371/journal.ppat.1014212 42133745 1553-7366 PMC13241007 https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014212 Cryptosporidium parvum, one of the leading causes of diarrheal death in children, remodels its infection site through secreted effector proteins. Several of them accumulate at the host-parasite interface, forming a complex structure whose function and importance for infection remain poorly understood. Here, we localized and functionally characterized the putative dense granule protein DG8. We confirmed the protein to be in the dense granules, forming a ring structure once secreted at the host-parasite interface. Deletion of DG8 showed reduced infection in mice in vivo and early defect in vitro, revealing the importance of DG8 for parasite fitness. Additional secreted proteins were identified as potential partners, among which SG4, a small granule protein, was shown to partially co-localize with DG8. Applying ultrastructure expansion microscopy on intestinal sections with newly generated antibodies against DG8 and SG4, we could precisely position the ring structure above the electron-dense band, around the feeder organelle at the base of the parasitophorous vacuole membrane with an unprecedent resolution. Altogether, better visualization and understanding of the host-parasite interface through expanded intestinal tissue and effectors characterization reveal a complex and essential layered host-parasite interface. Animals Cell Membrane / parasitology Cell Membrane / ultrastructure Cryptosporidiosis / metabolism Cryptosporidiosis / parasitology Cryptosporidium parvum / metabolism Cryptosporidium parvum / pathogenicity Epithelial Cells / parasitology Epithelial Cells / ultrastructure Host-Parasite Interactions Intestines / parasitology Intestines / ultrastructure Mice Mice, Inbred C57BL Protozoan Proteins / metabolism Vacuoles / parasitology Dewey 616 Swiss National Science Foundation Identification and functional characterization of Cryptosporidium secreted effectors hijacking host cellular functions 208568 CH 54 Département de microbiologie et médecine moléculaire 21B false 1411 Pouvoir pathogène du parasite cryptosporidium 1046 443 Biologie d'un parasite intracellulaire obligatoire 773 https://www.ebi.ac.uk/pride/archive/projects/PXD074689 PLOS pathogens 22 5 cba8f614-9b8b-4bfd-afe6-bb1ddda0217f Article (Published version) Public journal.ppat.1014212_(3).pdf 2536268 application/pdf CC BY-4.0 3373580a9edc5460ffc87cf1c1df1e0af60a23ceb76ce7eb0742b63e542a8df3 ba2199d7-b388-49d7-89b5-a5c3f57d51c8 Supplemental data Public 10_1371_journal_ppat_1014212.zip 8115616 application/zip ee7443b0b6e17f09a392e5ec7c3437789efeb54b8c8aa954c6bce626e79ccace openAccess Faculté de médecine / Section de médecine fondamentale / Département de microbiologie et médecine moléculaire

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Cryptosporidium secreted proteins form a complex layered interface with the host cell	PLOS pathogens			2026	9	15

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Moreno Sanchez, Sandra