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How deadly parasites choose to be male

By: Erica Moser Date: May 30, 2024
Image of Cryptosporidium
Penn Vet researchers developed the Cryptosporidium single-cell atlas, revealing which genes are expressed at which points across the parasite’s life cycle. On the left, the atlas shows parasites replicating asexually in green, with males in blue and females in pink. On the right, micrographs of the stages are shown, with their nuclei highlighted in green. (Image: Boris Striepen)

The single-cell parasite Cryptosporidium is a leading cause of deadly diarrheal disease in young children, and a recent outbreak in the United Kingdom highlights how vulnerable the water supply is to this pathogen. There are no effective drugs or vaccines, making this an important organism to study. The parasite infects the cells that line the intestines and engages in both asexual and sexual replication, which researchers suspect are both critical to sustained infection and transmission.

But the mechanism by which the parasite becomes male or female is unknown. “These parasites do not have sex chromosomes, like the human X or Y,” says Katelyn A. Walzer, a postdoctoral fellow in the Striepen Lab in Penn’s School of Veterinary Medicine. “Revealing how they choose a sex is of fundamental biological interest and provides a new key target to block transmission and infection.”

Walzer is the lead author of a study, published in Nature, that reveals the gene expression program of the entire Cryptosporidium life cycle. Using RNA sequencing, the researchers profiled more than 9,000 parasites—from infected cell cultures and mice—and developed the Cryptosporidium single-cell atlas, which reveals what genes are expressed at which points across the life cycle. In a second major finding, researchers identified the earliest determinant of maleness, a gene called Myb-M.

“We show in this and other work that the sexual part of this life cycle is critical to infection, and blocking it through parasite contraception will block the infection,” says senior author Boris Striepen. He says that by disrupting sex “we may be able to cure the disease or weaken the parasite to engineer a vaccine, so I think there’s a really strong translational potential.”

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