{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T13:16:45Z","timestamp":1753881405088,"version":"3.41.2"},"reference-count":44,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2017,9,19]],"date-time":"2017-09-19T00:00:00Z","timestamp":1505779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,11,8]],"date-time":"2017-11-08T00:00:00Z","timestamp":1510099200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2017,11,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>African trypanosomiasis is caused by infection with the protozoan parasite<jats:italic>Trypanosoma brucei<\/jats:italic>. During infection, this pathogen divides rapidly to high density in the bloodstream of its mammalian host in a manner similar to that of leukemia. Like all eukaryotes,<jats:italic>T.\u00a0brucei<\/jats:italic>has a cell cycle involving the<jats:italic>de novo<\/jats:italic>synthesis of DNA regulated by ribonucleotide reductase (RNR), which catalyzes the conversion of ribonucleotides into their deoxy form. As an essential enzyme for the cell cycle, RNR is a common target for cancer chemotherapy. We hypothesized that inhibition of RNR by genetic or pharmacological means would impair parasite growth<jats:italic>in vitro<\/jats:italic>and prolong the survival of infected animals. Our results demonstrate that RNR inhibition is highly effective in suppressing parasite growth both<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>. These results support drug discovery efforts targeting the cell cycle, not only for African trypanosomiasis but possibly also for other infections by eukaryotic pathogens.<\/jats:p><jats:p><jats:bold>IMPORTANCE<\/jats:bold>The development of drugs to treat infections with eukaryotic pathogens is challenging because many key virulence factors have closely related homologues in humans. Drug toxicity greatly limits these development efforts. For pathogens that replicate at a high rate, especially in the blood, an alternative approach is to target the cell cycle directly, much as is done to treat some hematologic malignancies. The results presented here indicate that targeting the cell cycle via inhibition of ribonucleotide reductase is effective at killing trypanosomes and prolonging the survival of infected animals.<\/jats:p>","DOI":"10.1128\/mbio.01427-17","type":"journal-article","created":{"date-parts":[[2017,9,20]],"date-time":"2017-09-20T00:10:27Z","timestamp":1505866227000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Cell Cycle Inhibition To Treat Sleeping Sickness"],"prefix":"10.1128","volume":"8","author":[{"given":"Conrad L.","family":"Epting","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Northwestern University, Chicago, Illinois, USA"},{"name":"Department of Pathology, Northwestern University, Chicago, Illinois, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian T.","family":"Emmer","sequence":"additional","affiliation":[{"name":"Department of Pathology, Northwestern University, Chicago, Illinois, USA"},{"name":"Department of Microbiology-Immunology, Northwestern University, Chicago, Illinois, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nga Y.","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Northwestern University, Chicago, Illinois, USA"},{"name":"Department of Pathology, Northwestern University, Chicago, Illinois, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joann M.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Northwestern University, Chicago, Illinois, USA"},{"name":"Department of Pathology, Northwestern University, Chicago, Illinois, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming Y.","family":"Makanji","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Northwestern University, Chicago, Illinois, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheryl L.","family":"Olson","sequence":"additional","affiliation":[{"name":"Department of Pathology, Northwestern University, Chicago, Illinois, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David M.","family":"Engman","sequence":"additional","affiliation":[{"name":"Department of Pathology, Northwestern University, Chicago, Illinois, USA"},{"name":"Department of Microbiology-Immunology, Northwestern University, Chicago, Illinois, USA"},{"name":"Department of Pathology and Laboratory Medicine, Cedars Sinai Medical Center, Los Angeles, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"doi-asserted-by":"publisher","key":"e_1_3_3_2_2","DOI":"10.1371\/journal.pntd.0000333"},{"key":"e_1_3_3_3_2","volume-title":"Trypanosomiasis, human African (sleeping sickness)","author":"World Health Organization","year":"2017","unstructured":"World Health Organization . 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