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Currently, there are no fully effective treatments or vaccines available. Parasite transmission occurs through ingestion of oocysts, through either direct contact or consumption of contaminated water or food. Oocysts are meiotic spores and the product of parasite sex.\n                    <jats:italic>Cryptosporidium<\/jats:italic>\n                    has a single-host life cycle in which both asexual and sexual processes occur in the intestine of infected hosts. Here, we genetically engineered strains of\n                    <jats:italic>Cryptosporidium<\/jats:italic>\n                    to make life cycle progression and parasite sex tractable. We derive reporter strains to follow parasite development in culture and in infected mice and define the genes that orchestrate sex and oocyst formation through mRNA sequencing of sorted cells. After 2\u2009d, parasites in cell culture show pronounced sexualization, but productive fertilization does not occur and infection falters. By contrast, in infected mice, male gametes successfully fertilize female parasites, which leads to meiotic division and sporulation. To rigorously test for fertilization, we devised a two-component genetic-crossing assay using a reporter that is activated by Cre recombinase. Our findings suggest obligate developmental progression towards sex in\n                    <jats:italic>Cryptosporidium<\/jats:italic>\n                    , which has important implications for the treatment and prevention of the infection.\n                  <\/jats:p>","DOI":"10.1038\/s41564-019-0539-x","type":"journal-article","created":{"date-parts":[[2019,9,2]],"date-time":"2019-09-02T14:11:06Z","timestamp":1567433466000},"page":"2226-2236","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":196,"title":["Life cycle progression and sexual development of the apicomplexan parasite Cryptosporidium parvum"],"prefix":"10.1038","volume":"4","author":[{"given":"Jayesh","family":"Tandel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth D.","family":"English","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Sateriale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jodi A.","family":"Gullicksrud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel P.","family":"Beiting","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan C.","family":"Sullivan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brittain","family":"Pinkston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7426-432X","authenticated-orcid":false,"given":"Boris","family":"Striepen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,9,2]]},"reference":[{"key":"539_CR1","doi-asserted-by":"crossref","first-page":"3027","DOI":"10.1016\/S0140-6736(16)31593-8","volume":"388","author":"L Liu","year":"2016","unstructured":"Liu, L. et al. Global, regional, and national causes of under-5 mortality in 2000-15: an updated systematic analysis with implications for the Sustainable Development Goals. Lancet 388, 3027\u20133035 (2016).","journal-title":"Lancet"},{"key":"539_CR2","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S0140-6736(13)60844-2","volume":"382","author":"KL Kotloff","year":"2013","unstructured":"Kotloff, K. L. et al. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study. Lancet 382, 209\u2013222 (2013).","journal-title":"Lancet"},{"key":"539_CR3","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S1473-3099(14)70772-8","volume":"15","author":"W Checkley","year":"2015","unstructured":"Checkley, W. et al. A review of the global burden, novel diagnostics, therapeutics, and vaccine targets for Cryptosporidium. Lancet Infect. Dis. 15, 85\u201394 (2015).","journal-title":"Lancet Infect. Dis."},{"key":"539_CR4","doi-asserted-by":"crossref","first-page":"E564","DOI":"10.1016\/S2214-109X(15)00151-5","volume":"3","author":"JA Platts-Mills","year":"2015","unstructured":"Platts-Mills, J. A. et al. Pathogen-specific burdens of community diarrhoea in developing countries: a multisite birth cohort study (MAL-ED). Lancet Glob. Health 3, E564\u2013E575 (2015).","journal-title":"Lancet Glob. Health"},{"key":"539_CR5","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.molmed.2012.04.007","volume":"18","author":"PS Korpe","year":"2012","unstructured":"Korpe, P. S. & Petri, W. A. Jr. Environmental enteropathy: critical implications of a poorly understood condition. Trends Mol. Med. 18, 328\u2013336 (2012).","journal-title":"Trends Mol. 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