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Program","award":["RC210291"],"award-info":[{"award-number":["RC210291"]}]},{"name":"Shenyang Young and middle-aged Scientific and technological Innovation Talent Support Program","award":["YDWS202209"],"award-info":[{"award-number":["YDWS202209"]}]},{"name":"Key Laboratory for prevention and control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, P.R. China and Key Laboratory of Livestock Disease Prevention of Guangdong Province","award":["2022YFD1800200"],"award-info":[{"award-number":["2022YFD1800200"]}]},{"name":"Key Laboratory for prevention and control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, P.R. China and Key Laboratory of Livestock Disease Prevention of Guangdong Province","award":["32072891"],"award-info":[{"award-number":["32072891"]}]},{"name":"Key Laboratory for prevention and control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, P.R. China and Key Laboratory of Livestock Disease Prevention of Guangdong Province","award":["31672546"],"award-info":[{"award-number":["31672546"]}]},{"name":"Key Laboratory for prevention and control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, P.R. China and Key Laboratory of Livestock Disease Prevention of Guangdong Province","award":["31902297"],"award-info":[{"award-number":["31902297"]}]},{"name":"Key Laboratory for prevention and control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, P.R. China and Key Laboratory of Livestock Disease Prevention of Guangdong Province","award":["LSNQN202003"],"award-info":[{"award-number":["LSNQN202003"]}]},{"name":"Key Laboratory for prevention and control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, P.R. China and Key Laboratory of Livestock Disease Prevention of Guangdong Province","award":["LJKZ0673"],"award-info":[{"award-number":["LJKZ0673"]}]},{"name":"Key Laboratory for prevention and control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, P.R. China and Key Laboratory of Livestock Disease Prevention of Guangdong Province","award":["RC210291"],"award-info":[{"award-number":["RC210291"]}]},{"name":"Key Laboratory for prevention and control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, P.R. China and Key Laboratory of Livestock Disease Prevention of Guangdong Province","award":["YDWS202209"],"award-info":[{"award-number":["YDWS202209"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Toxoplasma gondii is an obligate protozoon that can infect all warm-blooded animals including humans. T. gondii afflicts one-third of the human population and is a detriment to the health of livestock and wildlife. Thus far, traditional drugs such as pyrimethamine and sulfadiazine used to treat T. gondii infection are inadequate as therapeutics due to relapse, long treatment period, and low efficacy in parasite clearance. Novel, efficacious drugs have not been available. Lumefantrine, as an antimalarial, is effective in killing T. gondii but has no known mechanism of action. We combined metabolomics with transcriptomics to investigate how lumefantrine inhibits T. gondii growth. We identified significant alternations in transcripts and metabolites and their associated functional pathways that are attributed to lumefantrine treatment. RH tachyzoites were used to infect Vero cells for three hours and subsequently treated with 900 ng\/mL lumefantrine. Twenty-four hours post-drug treatment, we observed significant changes in transcripts associated with five DNA replication and repair pathways. Metabolomic data acquired through liquid chromatography-tandem mass spectrometry (LC-MS) showed that lumefantrine mainly affected sugar and amino acid metabolism, especially galactose and arginine. To investigate whether lumefantrine damages T. gondii DNA, we conducted a terminal transferase assay (TUNEL). TUNEL results showed that lumefantrine significantly induced apoptosis in a dose-dependent manner. Taken together, lumefantrine effectively inhibited T. gondii growth by damaging DNA, interfering with DNA replication and repair, and altering energy and amino acid metabolisms.<\/jats:p>","DOI":"10.3390\/ijms24054902","type":"journal-article","created":{"date-parts":[[2023,3,3]],"date-time":"2023-03-03T03:32:52Z","timestamp":1677814372000},"page":"4902","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A Metabolomic and Transcriptomic Study Revealed the Mechanisms of Lumefantrine Inhibition of Toxoplasma gondii"],"prefix":"10.3390","volume":"24","author":[{"given":"Meiqi","family":"Li","sequence":"first","affiliation":[{"name":"Key Laboratory of Livestock Infectious Diseases in Northeast China, Ministry of Education, Key Laboratory of Zoonosis, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Dongling Road 120, Shenyang 110866, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyu","family":"Sang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Livestock Infectious Diseases in Northeast China, Ministry of Education, Key Laboratory of Zoonosis, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Dongling Road 120, Shenyang 110866, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Livestock Infectious Diseases in Northeast China, Ministry of Education, Key Laboratory of Zoonosis, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Dongling Road 120, Shenyang 110866, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Livestock Infectious Diseases in Northeast China, Ministry of Education, Key Laboratory of Zoonosis, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Dongling Road 120, Shenyang 110866, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Feng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Livestock Infectious Diseases in Northeast China, Ministry of Education, Key Laboratory of Zoonosis, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Dongling Road 120, Shenyang 110866, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Livestock Infectious Diseases in Northeast China, Ministry of Education, Key Laboratory of Zoonosis, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Dongling Road 120, Shenyang 110866, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiantian","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, School of Medicine, University of California, La Jolla, San Diego, CA 92122, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,3]]},"reference":[{"key":"ref_1","first-page":"898","article-title":"Global status of Toxoplasma gondii infection: Systematic review and prevalence snapshots","volume":"36","author":"Molan","year":"2019","journal-title":"Trop Biomed."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1186\/1756-3305-4-165","article-title":"Toxoplasma gondii infection in humans in China","volume":"4","author":"Zhou","year":"2011","journal-title":"Parasit Vectors"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1186\/1756-3305-6-273","article-title":"Toxoplasma gondii prevalence in food animals 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