Cryptosporidium sex employs a complex male fertilization apparatus that is required for continued infection
- 1Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Abstract
Most apicomplexan parasites replicate asexually to colonize their mammalian hosts, and sexually in the context of transmission. In contrast, for Cryptosporidium sex is essential to sustain intestinal infection in vivo and therefore is a promising opportunity to prevent and treat the disease. However, the mechanism of sex, which occurs within host enterocytes, is poorly understood, limiting the discovery of targets for such intervention. Here we identify an elaborate fertilization apparatus and numerous of its molecular components in male gametes. We discern two elements, one displayed on the apex, that makes intimate contact with host cells containing female parasites, and a second internal structure, that harbors the membrane fusogen HAP2. Ablation of HAP2 by conditional mutagenesis blocked fertilization and oocyst production, rapidly cured infected mice and left them with enhanced resistance to subsequent challenge. Our studies provide insights into a remarkable fertilization mechanism and highlight specific molecules as targets for translation.
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BibTeX
@misc{balestra2026cryptosporidium,
title = {{Cryptosporidium sex employs a complex male fertilization apparatus that is required for continued infection}},
author = {A. C. Balestra and M. Merolle and T. Bergner and M. Tang and N. Y. Robles-Ramirez and A. Ndayiragije and B. A. Wallbank and A. M. Daniels and M. Laue and C. Klotz and C. A. Hunter and B. Striepen},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.13.757955},
url = {https://www.biorxiv.org/content/10.64898/2026.10.13.757955v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Cryptosporidium sex employs a complex male fertilization apparatus that is required for continued infection
AU - A. C. Balestra
AU - M. Merolle
AU - T. Bergner
AU - M. Tang
AU - N. Y. Robles-Ramirez
AU - A. Ndayiragije
AU - B. A. Wallbank
AU - A. M. Daniels
AU - M. Laue
AU - C. Klotz
AU - C. A. Hunter
AU - B. Striepen
PY - 2026
DA - 2026/10/13
PB - bioRxiv
DO - 10.64898/2026.10.13.757955
UR - https://www.biorxiv.org/content/10.64898/2026.10.13.757955v1
AB - Most apicomplexan parasites replicate asexually to colonize their mammalian hosts, and sexually in the context of transmission. In contrast, for Cryptosporidium sex is essential to sustain intestinal infection in vivo and therefore is a promising opportunity to prevent and treat the disease. However, the mechanism of sex, which occurs within host enterocytes, is poorly understood, limiting the discovery of targets for such intervention. Here we identify an elaborate fertilization apparatus and numerous of its molecular components in male gametes. We discern two elements, one displayed on the apex, that makes intimate contact with host cells containing female parasites, and a second internal structure, that harbors the membrane fusogen HAP2. Ablation of HAP2 by conditional mutagenesis blocked fertilization and oocyst production, rapidly cured infected mice and left them with enhanced resistance to subsequent challenge. Our studies provide insights into a remarkable fertilization mechanism and highlight specific molecules as targets for translation.
ER -