exports a mucin glycoprotein into the microvilli of intestinal epithelium.

Abstract

causes severe diarrhea in humans and animals. Mucin-like glycoproteins play a critical role in parasite attachment and invasion and therefore serve as potential protective antigens against reinfection. Muc25 is a highly polymorphic mucin that has been associated with differences in host infectivity in comparative genomic analyses. To study the function of Muc25, we determined its localization and secretion inby genome editing. Endogenous gene tagging revealed that Muc25 is stored in small granules of sporozoites and secreted into host microvilli after invasion. Deletion of the signal peptide affected Muc25 localization and secretion, as the Muc25ΔSP protein was localized to the membrane in sporozoites and remained within intracellular life stages. In addition, aknockout strain () was easily generated, indicating that Muc25 is not critical for parasite survival. However, thestrain showed reduced growth in HCT-8 cells, and the survival time was prolonged in GKO mice infected withcompared to those infected with Muc25-3 HA. Transcriptome analysis revealed thatparasites caused less damage to host cellsthan Muc25-3 HA parasites. Taken together, these data provide evidence for the export of aprotein to host microvilli and demonstrate that such manipulation of the host cell response may be involved in parasite pathogenesis.