{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T10:11:41Z","timestamp":1784887901953,"version":"3.55.0"},"reference-count":48,"publisher":"National Academy of Sciences","issue":"42","license":[{"start":{"date-parts":[[2019,9,30]],"date-time":"2019-09-30T00:00:00Z","timestamp":1569801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1183177"],"award-info":[{"award-number":["OPP1183177"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI125362"],"award-info":[{"award-number":["R01AI125362"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI112427"],"award-info":[{"award-number":["R01AI112427"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["T32AI060546"],"award-info":[{"award-number":["T32AI060546"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["F32AI124518"],"award-info":[{"award-number":["F32AI124518"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["K99AI137442"],"award-info":[{"award-number":["K99AI137442"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["T32AI007532"],"award-info":[{"award-number":["T32AI007532"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2019,10,15]]},"abstract":"<jats:p>\n                    The apicomplexan parasite\n                    <jats:italic>Cryptosporidium<\/jats:italic>\n                    is a leading global cause of severe diarrheal disease and an important contributor to early-childhood mortality. Waterborne outbreaks occur frequently, even in countries with advanced water treatment capabilities, and there is currently no fully effective treatment. Nucleotide pathways are attractive targets for antimicrobial development, and several laboratories are designing inhibitors of these enzymes as potential treatment for\n                    <jats:italic>Cryptosporidium<\/jats:italic>\n                    infections. Here we take advantage of newly available molecular genetics for\n                    <jats:italic>Cryptosporidium parvum<\/jats:italic>\n                    to investigate nucleotide biosynthesis by directed gene ablation. Surprisingly, we found that the parasite tolerates the loss of classical targets including dihydrofolate reductase-thymidylate synthase (DHFR-TS) and inosine monophosphate dehydrogenase (IMPDH). We show that thymidine kinase provides a route to thymidine monophosphate in the absence of DHFR-TS. In contrast, only a single pathway has been identified for\n                    <jats:italic>C. parvum<\/jats:italic>\n                    purine nucleotide salvage. Nonetheless, multiple enzymes in the purine pathway, as well as the adenosine transporter, can be ablated. The resulting mutants are viable under normal conditions but are hypersensitive to inhibition of purine nucleotide synthesis in their host cell.\n                    <jats:italic>Cryptosporidium<\/jats:italic>\n                    might use as-yet undiscovered purine transporters and salvage enzymes; however, genetic and pharmacological experiments led us to conclude that\n                    <jats:italic>Cryptosporidium<\/jats:italic>\n                    imports purine nucleotides from the host cell. The potential for ATP uptake from the host has significant impact on our understanding of parasite energy metabolism given that\n                    <jats:italic>Cryptosporidium<\/jats:italic>\n                    lacks oxidative phosphorylation and glycolytic enzymes are not constitutively expressed throughout the parasite life cycle.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1908239116","type":"journal-article","created":{"date-parts":[[2019,9,30]],"date-time":"2019-09-30T21:54:38Z","timestamp":1569880478000},"page":"21160-21165","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":78,"title":["Genetic ablation of purine salvage in\n                    <i>Cryptosporidium parvum<\/i>\n                    reveals nucleotide uptake from the host cell"],"prefix":"10.1073","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2002-6681","authenticated-orcid":false,"given":"Mattie C.","family":"Pawlowic","sequence":"first","affiliation":[{"name":"Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA 30602;"},{"name":"Department of Cellular Biology, University of Georgia, Athens, GA 30602;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mastanbabu","family":"Somepalli","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Sateriale","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian T.","family":"Herbert","sequence":"additional","affiliation":[{"name":"Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA 30602;"},{"name":"Department of Cellular Biology, University of Georgia, Athens, GA 30602;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis R.","family":"Gibson","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory D.","family":"Cuny","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lizbeth","family":"Hedstrom","sequence":"additional","affiliation":[{"name":"Department of Biology, Brandeis University, Waltham, MA 02454;"},{"name":"Department of Chemistry, Brandeis University, Waltham, MA 02454"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris","family":"Striepen","sequence":"additional","affiliation":[{"name":"Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA 30602;"},{"name":"Department of Cellular Biology, University of Georgia, Athens, GA 30602;"},{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2019,9,30]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S0140-6736(13)60844-2","article-title":"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","volume":"382","author":"Kotloff K. L.","year":"2013","unstructured":"K. L. Kotloff ., 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":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"e568","DOI":"10.1016\/S2214-109X(19)30076-2","article-title":"The incidence, aetiology, and adverse clinical consequences of less severe diarrhoeal episodes among infants and children residing in low-income and middle-income countries: A 12-month case-control study as a follow-on to the Global Enteric Multicenter Study (GEMS)","volume":"7","author":"Kotloff K. L.","year":"2019","unstructured":"K. L. Kotloff ., The incidence, aetiology, and adverse clinical consequences of less severe diarrhoeal episodes among infants and children residing in low-income and middle-income countries: A 12-month case-control study as a follow-on to the Global Enteric Multicenter Study (GEMS). Lancet Glob. Health 7, e568\u2013e584 (2019).","journal-title":"Lancet Glob. Health"},{"key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S1473-3099(14)70772-8","article-title":"A review of the global burden, novel diagnostics, therapeutics, and vaccine targets for Cryptosporidium","volume":"15","author":"Checkley W.","year":"2015","unstructured":"W. Checkley ., 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":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"e758","DOI":"10.1016\/S2214-109X(18)30283-3","article-title":"Morbidity, mortality, and long-term consequences associated with diarrhoea from Cryptosporidium infection in children younger than 5 years: A meta-analyses study","volume":"6","author":"Khalil I. A.","year":"2018","unstructured":"I. A. Khalil ., Morbidity, mortality, and long-term consequences associated with diarrhoea from Cryptosporidium infection in children younger than 5 years: A meta-analyses study. Lancet Glob. Health 6, e758\u2013e768 (2018).","journal-title":"Lancet Glob. Health"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/503189a","article-title":"Parasitic infections: Time to tackle cryptosporidiosis","volume":"503","author":"Striepen B.","year":"2013","unstructured":"B. Striepen, Parasitic infections: Time to tackle cryptosporidiosis. Nature 503, 189\u2013191 (2013).","journal-title":"Nature"},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1126\/science.1094786","article-title":"Complete genome sequence of the apicomplexan, Cryptosporidium parvum","volume":"304","author":"Abrahamsen M. S.","year":"2004","unstructured":"M. S. Abrahamsen ., Complete genome sequence of the apicomplexan, Cryptosporidium parvum. Science 304, 441\u2013445 (2004).","journal-title":"Science"},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1099\/00221287-146-2-315","article-title":"Cryptosporidium parvum appears to lack a plastid genome","volume":"146","author":"Zhu G.","year":"2000","unstructured":"G. Zhu, M. J. Marchewka, J. S. Keithly, Cryptosporidium parvum appears to lack a plastid genome. Microbiology 146, 315\u2013321 (2000).","journal-title":"Microbiology"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-019-0539-x"},{"key":"e_1_3_4_9_2","first-page":"57","volume-title":"Cryptosporidium and Cryptosporidiosis","author":"Zhu G.","year":"2007","unstructured":"G. Zhu, \u201cBiochemistry\u201d in Cryptosporidium and Cryptosporidiosis, R. Fayer, L. Xiao, Eds. (CRC Press, Boca Raton, FL, 2007), pp. 57\u201377."},{"key":"e_1_3_4_10_2","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/nature14651","article-title":"Genetic modification of the diarrhoeal pathogen Cryptosporidium parvum","volume":"523","author":"Vinayak S.","year":"2015","unstructured":"S. Vinayak ., Genetic modification of the diarrhoeal pathogen Cryptosporidium parvum. Nature 523, 477\u2013480 (2015).","journal-title":"Nature"},{"key":"e_1_3_4_11_2","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1016\/j.bmcl.2015.03.091","article-title":"A nanotherapy strategy significantly enhances anticryptosporidial activity of an inhibitor of bifunctional thymidylate synthase-dihydrofolate reductase from Cryptosporidium","volume":"25","author":"Mukerjee A.","year":"2015","unstructured":"A. Mukerjee ., A nanotherapy strategy significantly enhances anticryptosporidial activity of an inhibitor of bifunctional thymidylate synthase-dihydrofolate reductase from Cryptosporidium. Bioorg. Med. Chem. Lett. 25, 2065\u20132067 (2015).","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"e_1_3_4_12_2","doi-asserted-by":"crossref","first-page":"e794","DOI":"10.1371\/journal.pntd.0000794","article-title":"A screening pipeline for antiparasitic agents targeting Cryptosporidium inosine monophosphate dehydrogenase","volume":"4","author":"Sharling L.","year":"2010","unstructured":"L. Sharling ., A screening pipeline for antiparasitic agents targeting Cryptosporidium inosine monophosphate dehydrogenase. PLoS Negl. Trop. Dis. 4, e794 (2010).","journal-title":"PLoS Negl. Trop. Dis."},{"key":"e_1_3_4_13_2","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S1359-6446(04)03308-2","article-title":"Targeting DHFR in parasitic protozoa","volume":"10","author":"Anderson A. C.","year":"2005","unstructured":"A. C. Anderson, Targeting DHFR in parasitic protozoa. Drug Discov. Today 10, 121\u2013128 (2005).","journal-title":"Drug Discov. Today"},{"key":"e_1_3_4_14_2","doi-asserted-by":"crossref","first-page":"3154","DOI":"10.1073\/pnas.0304686101","article-title":"Gene transfer in the evolution of parasite nucleotide biosynthesis","volume":"101","author":"Striepen B.","year":"2004","unstructured":"B. Striepen ., Gene transfer in the evolution of parasite nucleotide biosynthesis. Proc. Natl. Acad. Sci. U.S.A. 101, 3154\u20133159 (2004).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"e_1_3_4_15_2","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/0065-2571(94)90025-6","article-title":"The methotrexate story: A paradigm for development of cancer chemotherapeutic agents","volume":"34","author":"Huennekens F. M.","year":"1994","unstructured":"F. M. Huennekens, The methotrexate story: A paradigm for development of cancer chemotherapeutic agents. Adv. Enzyme Regul. 34, 397\u2013419 (1994).","journal-title":"Adv. Enzyme Regul."},{"key":"e_1_3_4_16_2","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.2174\/092986711795590129","article-title":"The antibiotic potential of prokaryotic IMP dehydrogenase inhibitors","volume":"18","author":"Hedstrom L.","year":"2011","unstructured":"L. Hedstrom, G. Liechti, J. B. Goldberg, D. R. Gollapalli, The antibiotic potential of prokaryotic IMP dehydrogenase inhibitors. Curr. Med. Chem. 18, 1909\u20131918 (2011).","journal-title":"Curr. Med. Chem."},{"key":"e_1_3_4_17_2","doi-asserted-by":"crossref","first-page":"6304","DOI":"10.1073\/pnas.092525699","article-title":"Genetic complementation in apicomplexan parasites","volume":"99","author":"Striepen B.","year":"2002","unstructured":"B. Striepen ., Genetic complementation in apicomplexan parasites. Proc. Natl. Acad. Sci. U.S.A. 99, 6304\u20136309 (2002).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"e_1_3_4_18_2","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.chembiol.2007.12.010","article-title":"Targeting a prokaryotic protein in a eukaryotic pathogen: Identification of lead compounds against cryptosporidiosis","volume":"15","author":"Umejiego N. N.","year":"2008","unstructured":"N. N. Umejiego ., Targeting a prokaryotic protein in a eukaryotic pathogen: Identification of lead compounds against cryptosporidiosis. Chem. Biol. 15, 70\u201377 (2008).","journal-title":"Chem. Biol."},{"key":"e_1_3_4_19_2","doi-asserted-by":"crossref","first-page":"4028","DOI":"10.1021\/jm400241j","article-title":"Optimization of benzoxazole-based inhibitors of Cryptosporidium parvum inosine 5\u2032-monophosphate dehydrogenase","volume":"56","author":"Gorla S. K.","year":"2013","unstructured":"S. K. Gorla ., Optimization of benzoxazole-based inhibitors of Cryptosporidium parvum inosine 5\u2032-monophosphate dehydrogenase. J. Med. Chem. 56, 4028\u20134043 (2013).","journal-title":"J. Med. Chem."},{"key":"e_1_3_4_20_2","doi-asserted-by":"crossref","first-page":"7759","DOI":"10.1021\/jm3007917","article-title":"Selective and potent urea inhibitors of Cryptosporidium parvum inosine 5\u2032-monophosphate dehydrogenase","volume":"55","author":"Gorla S. K.","year":"2012","unstructured":"S. K. Gorla ., Selective and potent urea inhibitors of Cryptosporidium parvum inosine 5\u2032-monophosphate dehydrogenase. J. Med. Chem. 55, 7759\u20137771 (2012).","journal-title":"J. Med. Chem."},{"key":"e_1_3_4_21_2","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1016\/j.bmcl.2012.01.029","article-title":"Structure-activity relationship study of selective benzimidazole-based inhibitors of Cryptosporidium parvum IMPDH","volume":"22","author":"Kirubakaran S.","year":"2012","unstructured":"S. Kirubakaran ., Structure-activity relationship study of selective benzimidazole-based inhibitors of Cryptosporidium parvum IMPDH. Bioorg. Med. Chem. Lett. 22, 1985\u20131988 (2012).","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"e_1_3_4_22_2","doi-asserted-by":"crossref","first-page":"4623","DOI":"10.1021\/jm900410u","article-title":"Triazole inhibitors of Cryptosporidium parvum inosine 5\u2032-monophosphate dehydrogenase","volume":"52","author":"Maurya S. K.","year":"2009","unstructured":"S. K. Maurya ., Triazole inhibitors of Cryptosporidium parvum inosine 5\u2032-monophosphate dehydrogenase. J. Med. Chem. 52, 4623\u20134630 (2009).","journal-title":"J. Med. Chem."},{"key":"e_1_3_4_23_2","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1006\/prep.2001.1610","article-title":"Purification and characterization of recombinant Plasmodium falciparum adenylosuccinate synthetase expressed in Escherichia coli","volume":"25","author":"Jayalakshmi R.","year":"2002","unstructured":"R. Jayalakshmi, K. Sumathy, H. Balaram, Purification and characterization of recombinant Plasmodium falciparum adenylosuccinate synthetase expressed in Escherichia coli. Protein Expr. Purif. 25, 65\u201372 (2002).","journal-title":"Protein Expr. Purif."},{"key":"e_1_3_4_24_2","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.bbapap.2008.11.021","article-title":"Elucidation of the substrate specificity, kinetic and catalytic mechanism of adenylosuccinate lyase from Plasmodium falciparum","volume":"1794","author":"Bulusu V.","year":"2009","unstructured":"V. Bulusu, B. Srinivasan, M. P. Bopanna, H. Balaram, Elucidation of the substrate specificity, kinetic and catalytic mechanism of adenylosuccinate lyase from Plasmodium falciparum. Biochim. Biophys. Acta 1794, 642\u2013654 (2009).","journal-title":"Biochim. Biophys. Acta"},{"key":"e_1_3_4_25_2","doi-asserted-by":"crossref","first-page":"eaap7847","DOI":"10.1126\/science.aap7847","article-title":"Uncovering the essential genes of the human malaria parasite Plasmodium falciparum by saturation mutagenesis","volume":"360","author":"Zhang M.","year":"2018","unstructured":"M. Zhang ., Uncovering the essential genes of the human malaria parasite Plasmodium falciparum by saturation mutagenesis. Science 360, eaap7847 (2018).","journal-title":"Science"},{"key":"e_1_3_4_26_2","doi-asserted-by":"crossref","first-page":"31221","DOI":"10.1074\/jbc.M404232200","article-title":"Purine salvage pathways in the apicomplexan parasite Toxoplasma gondii","volume":"279","author":"Chaudhary K.","year":"2004","unstructured":"K. Chaudhary ., Purine salvage pathways in the apicomplexan parasite Toxoplasma gondii. J. Biol. Chem. 279, 31221\u201331227 (2004).","journal-title":"J. Biol. Chem."},{"key":"e_1_3_4_27_2","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/S0166-6851(99)00109-7","article-title":"Recombinant expression, purification, and characterization of Toxoplasma gondii adenosine kinase","volume":"103","author":"Darling J. A.","year":"1999","unstructured":"J. A. Darling, W. J. SullivanJr, D. Carter, B. Ullman, D. S. Roos, Recombinant expression, purification, and characterization of Toxoplasma gondii adenosine kinase. Mol. Biochem. Parasitol. 103, 15\u201323 (1999).","journal-title":"Mol. Biochem. Parasitol."},{"key":"e_1_3_4_28_2","first-page":"35255","article-title":"The adenosine transporter of Toxoplasma gondii. Identification by insertional mutagenesis, cloning, and recombinant expression","volume":"274","author":"Chiang C. W.","year":"1999","unstructured":"C. W. Chiang ., The adenosine transporter of Toxoplasma gondii. Identification by insertional mutagenesis, cloning, and recombinant expression. J. Biol. Chem. 274, 35255\u201335261 (1999).","journal-title":"J. Biol. Chem."},{"key":"e_1_3_4_29_2","doi-asserted-by":"crossref","first-page":"3015","DOI":"10.1073\/pnas.82.9.3015","article-title":"Cloning and expression of the Rickettsia prowazekii ADP\/ATP translocator in Escherichia coli","volume":"82","author":"Krause D. C.","year":"1985","unstructured":"D. C. Krause, H. H. Winkler, D. O. Wood, Cloning and expression of the Rickettsia prowazekii ADP\/ATP translocator in Escherichia coli. Proc. Natl. Acad. Sci. U.S.A. 82, 3015\u20133019 (1985).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"e_1_3_4_30_2","doi-asserted-by":"crossref","first-page":"545","DOI":"10.2174\/092986730607220401122519","article-title":"IMP dehydrogenase: Mechanism of action and inhibition","volume":"6","author":"Hedstrom L.","year":"1999","unstructured":"L. Hedstrom, IMP dehydrogenase: Mechanism of action and inhibition. Curr. Med. Chem. 6, 545\u2013560 (1999).","journal-title":"Curr. Med. Chem."},{"key":"e_1_3_4_31_2","doi-asserted-by":"crossref","first-page":"15388","DOI":"10.1021\/bi991558q","article-title":"Species-specific inhibition of inosine 5\u2032-monophosphate dehydrogenase by mycophenolic acid","volume":"38","author":"Digits J. A.","year":"1999","unstructured":"J. A. Digits, L. Hedstrom, Species-specific inhibition of inosine 5\u2032-monophosphate dehydrogenase by mycophenolic acid. Biochemistry 38, 15388\u201315397 (1999).","journal-title":"Biochemistry"},{"key":"e_1_3_4_32_2","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1016\/j.chembiol.2010.07.014","article-title":"Structural determinants of inhibitor selectivity in prokaryotic IMP dehydrogenases","volume":"17","author":"Gollapalli D. R.","year":"2010","unstructured":"D. R. Gollapalli ., Structural determinants of inhibitor selectivity in prokaryotic IMP dehydrogenases. Chem. Biol. 17, 1084\u20131091 (2010).","journal-title":"Chem. Biol."},{"key":"e_1_3_4_33_2","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1021\/ja909947a","article-title":"The structural basis of Cryptosporidium-specific IMP dehydrogenase inhibitor selectivity","volume":"132","author":"Macpherson I. S.","year":"2010","unstructured":"I. S. Macpherson ., The structural basis of Cryptosporidium-specific IMP dehydrogenase inhibitor selectivity. J. Am. Chem. Soc. 132, 1230\u20131231 (2010).","journal-title":"J. Am. Chem. Soc."},{"key":"e_1_3_4_34_2","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1016\/S0092-8674(00)81275-1","article-title":"Structure and mechanism of inosine monophosphate dehydrogenase in complex with the immunosuppressant mycophenolic acid","volume":"85","author":"Sintchak M. D.","year":"1996","unstructured":"M. D. Sintchak ., Structure and mechanism of inosine monophosphate dehydrogenase in complex with the immunosuppressant mycophenolic acid. Cell 85, 921\u2013930 (1996).","journal-title":"Cell"},{"key":"e_1_3_4_35_2","doi-asserted-by":"crossref","first-page":"40320","DOI":"10.1074\/jbc.M407121200","article-title":"Cryptosporidium parvum IMP dehydrogenase: Identification of functional, structural, and dynamic properties that can be exploited for drug design","volume":"279","author":"Umejiego N. N.","year":"2004","unstructured":"N. N. Umejiego, C. Li, T. Riera, L. Hedstrom, B. Striepen, Cryptosporidium parvum IMP dehydrogenase: Identification of functional, structural, and dynamic properties that can be exploited for drug design. J. Biol. Chem. 279, 40320\u201340327 (2004).","journal-title":"J. Biol. Chem."},{"key":"e_1_3_4_36_2","doi-asserted-by":"crossref","first-page":"14010","DOI":"10.1074\/jbc.271.24.14010","article-title":"Insertional tagging, cloning, and expression of the Toxoplasma gondii hypoxanthine-xanthine-guanine phosphoribosyltransferase gene. Use as a selectable marker for stable transformation","volume":"271","author":"Donald R. G. K.","year":"1996","unstructured":"R. G. K. Donald, D. Carter, B. Ullman, D. S. Roos, Insertional tagging, cloning, and expression of the Toxoplasma gondii hypoxanthine-xanthine-guanine phosphoribosyltransferase gene. Use as a selectable marker for stable transformation. J. Biol. Chem. 271, 14010\u201314019 (1996).","journal-title":"J. Biol. Chem."},{"key":"e_1_3_4_37_2","doi-asserted-by":"crossref","first-page":"993","DOI":"10.2307\/3279197","article-title":"Arabinosyl nucleosides inhibit Toxoplasma gondii and allow the selection of resistant mutants","volume":"62","author":"Pfefferkorn E. R.","year":"1976","unstructured":"E. R. Pfefferkorn, L. C. Pfefferkorn, Arabinosyl nucleosides inhibit Toxoplasma gondii and allow the selection of resistant mutants. J. Parasitol. 62, 993\u2013999 (1976).","journal-title":"J. Parasitol."},{"key":"e_1_3_4_38_2","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.molbiopara.2006.06.001","article-title":"Adenosine kinase from Cryptosporidium parvum","volume":"149","author":"Galazka J.","year":"2006","unstructured":"J. Galazka, B. Striepen, B. Ullman, Adenosine kinase from Cryptosporidium parvum. Mol. Biochem. Parasitol. 149, 223\u2013230 (2006).","journal-title":"Mol. Biochem. Parasitol."},{"key":"e_1_3_4_39_2","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1002\/cbic.201200253","article-title":"Metabolic labeling of DNA by purine analogues in vivo","volume":"13","author":"Neef A. B.","year":"2012","unstructured":"A. B. Neef, F. Samain, N. W. Luedtke, Metabolic labeling of DNA by purine analogues in vivo. ChemBioChem 13, 1750\u20131753 (2012).","journal-title":"ChemBioChem"},{"key":"e_1_3_4_40_2","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1016\/j.cell.2016.08.019","article-title":"A genome-wide CRISPR screen in Toxoplasma identifies essential apicomplexan genes","volume":"166","author":"Sidik S. M.","year":"2016","unstructured":"S. M. Sidik ., A genome-wide CRISPR screen in Toxoplasma identifies essential apicomplexan genes. Cell 166, 1423\u20131435.e12 (2016).","journal-title":"Cell"},{"key":"e_1_3_4_41_2","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1128\/JB.181.4.1196-1202.1999","article-title":"Two nucleotide transport proteins in Chlamydia trachomatis, one for net nucleoside triphosphate uptake and the other for transport of energy","volume":"181","author":"Tjaden J.","year":"1999","unstructured":"J. Tjaden ., Two nucleotide transport proteins in Chlamydia trachomatis, one for net nucleoside triphosphate uptake and the other for transport of energy. J. Bacteriol. 181, 1196\u20131202 (1999).","journal-title":"J. Bacteriol."},{"key":"e_1_3_4_42_2","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1038\/nature06903","article-title":"A novel route for ATP acquisition by the remnant mitochondria of Encephalitozoon cuniculi","volume":"453","author":"Tsaousis A. D.","year":"2008","unstructured":"A. D. Tsaousis ., A novel route for ATP acquisition by the remnant mitochondria of Encephalitozoon cuniculi. Nature 453, 553\u2013556 (2008).","journal-title":"Nature"},{"key":"e_1_3_4_43_2","doi-asserted-by":"crossref","first-page":"e47037","DOI":"10.7554\/eLife.47037","article-title":"A new family of cell surface located purine transporters in Microsporidia and related fungal endoparasites","volume":"8","author":"Major P.","year":"2019","unstructured":"P. Major ., A new family of cell surface located purine transporters in Microsporidia and related fungal endoparasites. eLife 8, e47037 (2019).","journal-title":"eLife"},{"key":"e_1_3_4_44_2","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1093\/gbe\/evq022","article-title":"The reduced genome of the parasitic microsporidian Enterocytozoon bieneusi lacks genes for core carbon metabolism","volume":"2","author":"Keeling P. J.","year":"2010","unstructured":"P. J. Keeling ., The reduced genome of the parasitic microsporidian Enterocytozoon bieneusi lacks genes for core carbon metabolism. Genome Biol. Evol. 2, 304\u2013309 (2010).","journal-title":"Genome Biol. Evol."},{"key":"e_1_3_4_45_2","doi-asserted-by":"crossref","first-page":"3194","DOI":"10.1016\/S0021-9258(18)94050-0","article-title":"Metabolic interconnection between the human malarial parasite Plasmodium falciparum and its host erythrocyte. Regulation of ATP levels by means of an adenylate translocator and adenylate kinase","volume":"264","author":"Kanaani J.","year":"1989","unstructured":"J. Kanaani, H. Ginsburg, Metabolic interconnection between the human malarial parasite Plasmodium falciparum and its host erythrocyte. Regulation of ATP levels by means of an adenylate translocator and adenylate kinase. J. Biol. Chem. 264, 3194\u20133199 (1989).","journal-title":"J. Biol. Chem."},{"key":"e_1_3_4_46_2","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with Burrows-Wheeler transform","volume":"25","author":"Li H.","year":"2009","unstructured":"H. Li, R. Durbin, Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25, 1754\u20131760 (2009).","journal-title":"Bioinformatics"},{"key":"e_1_3_4_47_2","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1101\/gr.107524.110","article-title":"The genome analysis toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data","volume":"20","author":"McKenna A.","year":"2010","unstructured":"A. McKenna ., The genome analysis toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 20, 1297\u20131303 (2010).","journal-title":"Genome Res."},{"key":"e_1_3_4_48_2","doi-asserted-by":"crossref","first-page":"1804","DOI":"10.1128\/AAC.02460-12","article-title":"Drug repurposing screen reveals FDA-approved inhibitors of human HMG-CoA reductase and isoprenoid synthesis that block Cryptosporidium parvum growth","volume":"57","author":"Bessoff K.","year":"2013","unstructured":"K. Bessoff, A. Sateriale, K. K. Lee, C. D. Huston, Drug repurposing screen reveals FDA-approved inhibitors of human HMG-CoA reductase and isoprenoid synthesis that block Cryptosporidium parvum growth. Antimicrob. Agents Chemother. 57, 1804\u20131814 (2013).","journal-title":"Antimicrob. Agents Chemother."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.1908239116","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1908239116","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T17:04:16Z","timestamp":1654621456000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1908239116"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,30]]},"references-count":48,"journal-issue":{"issue":"42","published-print":{"date-parts":[[2019,10,15]]}},"alternative-id":["10.1073\/pnas.1908239116"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1908239116","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,30]]},"assertion":[{"value":"2019-09-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}