A Screen for Cryptosporidium Rhoptry Proteins Identifies ROP1 as an Effector Targeting the Host Cytoskeletal Modulator LMO7

The parasite Cryptosporidium invades and replicates in intestinal epithelial cells and is a leading cause of diarrheal disease and early childhood mortality. The molecular mechanisms that underlie infection and pathogenesis are largely unknown. Here we delineate the events of host cell invasion and uncover a mechanism unique to Cryptosporidium. We develop a screen to identify parasite effectors and show injection of multiple parasite proteins into the host from the rhoptry organelle. These factors are targeted to diverse locations within the host cell and its interface with the parasite. One of them, ROP1 accumulates in the enterocyte’s terminal web through direct interaction with the host protein LMO7, an organizer of epithelial cell polarity and cell-cell adhesion. Genetic ablation of LMO7 and ROP1 in mice and parasites respectively, show that both impact parasite burden in vivo. Taken together, these studies provide molecular insight into how Cryptosporidium manipulates its intestinal host niche.