Using To Model Fecal-Oral Transmission of in Mice.

There are several species that colonize humans, but only Entamoeba histolytica causes severe disease. E. histolytica is transmitted through the fecal-oral route to colonize the intestinal tract of 50 million people worldwide. The current mouse model to study E. histolytica intestinal infection directly delivers the parasite into the surgically exposed cecum, which circumvents the natural route of infection. To develop a fecal-oral mouse model, we screened our vivarium for a natural murine colonizer via a pan- PCR targeting the 18S ribosomal gene. We determined that C57BL/6 mice were chronically colonized by This amoeba is closely related to E. histolytica, as determined by 18S sequencing and cross-reactivity with an E. histolytica-specific antibody. In contrast, outbred Swiss Webster (SW) mice were not chronically colonized by We orally challenged SW mice with 1 × 10 cysts and discovered they were susceptible to infection, with peak cyst shedding occurring between 5 and 7 days postinfection. Most infected SW mice did not lose weight significantly but trended toward decreased weight gain throughout the experiment compared to mock-infected controls. Infected mice treated with paromomycin, an antibiotic used against noninvasive intestinal disease, do not become colonized by . Within the intestinal tract, localizes exclusively to the cecum and colon. Purified cysts treated with bovine bile excyst into mobile, pretrophozoite stages. Overall, this work describes a novel fecal-oral mouse model for the important global pathogen E. histolytica. Infection with parasites from the genus are significantly underreported causes of diarrheal disease that disproportionally impact tropical regions. There are several species of that infect humans to cause a range of symptoms from asymptomatic colonization of the intestinal tract to invasive disease with dissemination. All species are spread via the fecal-oral route in contaminated food and water. Studying the life cycle of , from host colonization to infectious fecal cyst production, can provide targets for vaccine and drug development. Because there is not an oral challenge rodent model, we screened for a mouse species and identified as a natural colonizer. We determine the peak of infection after an oral challenge, the efficacy of paromomycin treatment, the intestinal tract localization, and the cues that trigger excystation. This oral infection mouse model will be valuable for the development of novel therapeutic options for infections.