{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T21:12:06Z","timestamp":1789679526531,"version":"4.0.1"},"update-to":[{"DOI":"10.1371\/journal.ppat.1011517","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T00:00:00Z","timestamp":1691107200000}}],"reference-count":71,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2023,7,20]],"date-time":"2023-07-20T00:00:00Z","timestamp":1689811200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012539","name":"Research School of Biology, Australian National University","doi-asserted-by":"publisher","award":["Innovation Grant"],"award-info":[{"award-number":["Innovation Grant"]}],"id":[{"id":"10.13039\/501100012539","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GNT1182369"],"award-info":[{"award-number":["GNT1182369"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["DP180103212"],"award-info":[{"award-number":["DP180103212"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015539","name":"Australian Government","doi-asserted-by":"crossref","award":["Australian Government Research Training Program Scholarship"],"award-info":[{"award-number":["Australian Government Research Training Program Scholarship"]}],"id":[{"id":"10.13039\/100015539","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Apicomplexans are widespread parasites of humans and other animals, and include the causative agents of malaria (\n                    <jats:italic>Plasmodium<\/jats:italic>\n                    species) and toxoplasmosis (\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    ). Existing anti-apicomplexan therapies are beset with issues around drug resistance and toxicity, and new treatment options are needed. The mitochondrial electron transport chain (ETC) is one of the few processes that has been validated as a drug target in apicomplexans. To identify new inhibitors of the apicomplexan ETC, we developed a Seahorse XFe96 flux analyzer approach to screen the 400 compounds contained within the Medicines for Malaria Venture \u2018Pathogen Box\u2019 for ETC inhibition. We identified six chemically diverse, on-target inhibitors of the ETC in\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>gondii<\/jats:italic>\n                    , at least four of which also target the ETC of\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    . Two of the identified compounds (MMV024937 and MMV688853) represent novel ETC inhibitor chemotypes. MMV688853 belongs to a compound class, the aminopyrazole carboxamides, that were shown previously to target a kinase with a key role in parasite invasion of host cells. Our data therefore reveal that MMV688853 has dual targets in apicomplexans. We further developed our approach to pinpoint the molecular targets of these inhibitors, demonstrating that all target Complex III of the ETC, with MMV688853 targeting the ubiquinone reduction (Q\n                    <jats:sub>i<\/jats:sub>\n                    ) site of the complex. Most of the compounds we identified remain effective inhibitors of parasites that are resistant to Complex III inhibitors that are in clinical use or development, indicating that they could be used in treating drug resistant parasites. In sum, we have developed a versatile, scalable approach to screen for compounds that target the ETC in apicomplexan parasites, and used this to identify and characterize novel inhibitors.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1011517","type":"journal-article","created":{"date-parts":[[2023,7,20]],"date-time":"2023-07-20T14:11:35Z","timestamp":1689862295000},"page":"e1011517","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":16,"title":["A screen of drug-like molecules identifies chemically diverse electron transport chain inhibitors in apicomplexan parasites"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8228-8797","authenticated-orcid":true,"given":"Jenni A.","family":"Hayward","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8205-0268","authenticated-orcid":true,"given":"F. Victor","family":"Makota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Cihalova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel A.","family":"Leonard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8036-9531","authenticated-orcid":true,"given":"Esther","family":"Rajendran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2130-3820","authenticated-orcid":true,"given":"Soraya M.","family":"Zwahlen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Shuttleworth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursula","family":"Wiedemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8156-7070","authenticated-orcid":true,"given":"Christina","family":"Spry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3345-8440","authenticated-orcid":true,"given":"Kevin J.","family":"Saliba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7369-1058","authenticated-orcid":true,"given":"Alexander G.","family":"Maier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2455-9821","authenticated-orcid":true,"given":"Giel G.","family":"van Dooren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,7,20]]},"reference":[{"issue":"9425","key":"ppat.1011517.ref001","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1016\/S0140-6736(04)16412-X","article-title":"Toxoplasmosis","volume":"363","author":"JG Montoya","year":"2004","journal-title":"Lancet"},{"key":"ppat.1011517.ref002","author":"WHO","year":"2021","journal-title":"World Malaria Report 2021. Geneva"},{"key":"ppat.1011517.ref003","doi-asserted-by":"crossref","first-page":"273","DOI":"10.2147\/DDDT.S60973","article-title":"Drugs in development for toxoplasmosis: advances, challenges, and current status","volume":"11","author":"PH Alday","year":"2017","journal-title":"Drug Des Devel Ther"},{"issue":"3","key":"ppat.1011517.ref004","doi-asserted-by":"crossref","first-page":"EI10\u20130013","DOI":"10.1128\/microbiolspec.EI10-0013-2016","article-title":"Artemisinin-Resistant Plasmodium falciparum Malaria","volume":"4","author":"RM Fairhurst","year":"2016","journal-title":"Microbiol Spectr"},{"issue":"3","key":"ppat.1011517.ref005","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.pt.2016.10.002","article-title":"Is the Mitochondrion a Good Malaria Drug Target?","volume":"33","author":"CD Goodman","year":"2017","journal-title":"Trends Parasitol"},{"key":"ppat.1011517.ref006","doi-asserted-by":"crossref","first-page":"111204","DOI":"10.1016\/j.molbiopara.2019.111204","article-title":"Same same, but different: Uncovering unique features of the mitochondrial respiratory chain of apicomplexans","volume":"232","author":"JA Hayward","year":"2019","journal-title":"Mol Biochem Parasitol"},{"issue":"2","key":"ppat.1011517.ref007","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/0014-5793(75)80359-0","article-title":"The protonmotive Q cycle: a general formulation","volume":"59","author":"P. Mitchell","year":"1975","journal-title":"FEBS Lett"},{"issue":"9","key":"ppat.1011517.ref008","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1038\/nrm2959","article-title":"Mitochondrial protein import: from proteomics to functional mechanisms","volume":"11","author":"O Schmidt","year":"2010","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"7131","key":"ppat.1011517.ref009","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/nature05572","article-title":"Specific role of mitochondrial electron transport in blood-stage Plasmodium falciparum","volume":"446","author":"HJ Painter","year":"2007","journal-title":"Nature"},{"issue":"7","key":"ppat.1011517.ref010","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1016\/0006-2952(92)90213-3","article-title":"Site of action of the antimalarial hydroxynaphthoquinone, 2-[trans-4-(4\u2019-chlorophenyl) cyclohexyl]-3-hydroxy-1,4-naphthoquinone (566C80)","volume":"43","author":"M Fry","year":"1992","journal-title":"Biochem Pharmacol"},{"issue":"39","key":"ppat.1011517.ref011","doi-asserted-by":"crossref","first-page":"15936","DOI":"10.1073\/pnas.1208069109","article-title":"Endochin-like quinolones are highly efficacious against acute and latent experimental toxoplasmosis","volume":"109","author":"JS Doggett","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"ppat.1011517.ref012","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1128\/AAC.04149-14","article-title":"Subtle changes in endochin-like quinolone structure alter the site of inhibition within the cytochrome bc1 complex of Plasmodium falciparum","volume":"59","author":"AM Stickles","year":"2015","journal-title":"Antimicrob Agents Chemother"},{"issue":"4","key":"ppat.1011517.ref013","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.cbpa.2010.05.005","article-title":"Inhibiting Plasmodium cytochrome bc1: a complex issue","volume":"14","author":"V Barton","year":"2010","journal-title":"Curr Opin Chem Biol"},{"issue":"1","key":"ppat.1011517.ref014","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0166-6851(93)90088-F","article-title":"Structural features of Plasmodium cytochrome b that may underlie susceptibility to 8-aminoquinolines and hydroxynaphthoquinones","volume":"58","author":"AB Vaidya","year":"1993","journal-title":"Mol Biochem Parasitol"},{"issue":"13","key":"ppat.1011517.ref015","doi-asserted-by":"crossref","first-page":"9731","DOI":"10.1074\/jbc.M111.324319","article-title":"Cytochrome b mutation Y268S conferring atovaquone resistance phenotype in malaria parasite results in reduced parasite bc1 catalytic turnover and protein expression","volume":"287","author":"N Fisher","year":"2012","journal-title":"J Biol Chem"},{"issue":"18","key":"ppat.1011517.ref016","doi-asserted-by":"crossref","first-page":"2935","DOI":"10.1002\/1873-3468.13868","article-title":"The cytochrome bc(1) complex as an antipathogenic target","volume":"594","author":"N Fisher","year":"2020","journal-title":"FEBS Lett"},{"issue":"3","key":"ppat.1011517.ref017","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.parint.2014.09.011","article-title":"Direct evidence for the atovaquone action on the Plasmodium cytochrome bc1 complex","volume":"64","author":"JE Siregar","year":"2015","journal-title":"Parasitol Int"},{"issue":"177","key":"ppat.1011517.ref018","doi-asserted-by":"crossref","first-page":"177ra37","DOI":"10.1126\/scitranslmed.3005029","article-title":"Quinolone-3-diarylethers: a new class of antimalarial drug","volume":"5","author":"A Nilsen","year":"2013","journal-title":"Sci Transl Med"},{"issue":"1","key":"ppat.1011517.ref019","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0166-6851(00)00184-5","article-title":"Characterization of cytochrome b from Toxoplasma gondii and Q(o) domain mutations as a mechanism of atovaquone-resistance","volume":"108","author":"DC McFadden","year":"2000","journal-title":"Mol Biochem Parasitol"},{"issue":"4","key":"ppat.1011517.ref020","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1046\/j.1365-2958.1999.01515.x","article-title":"Resistance mutations reveal the atovaquone-binding domain of cytochrome b in malaria parasites","volume":"33","author":"IK Srivastava","year":"1999","journal-title":"Mol Microbiol"},{"issue":"5","key":"ppat.1011517.ref021","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1128\/AAC.48.5.1803-1806.2004","article-title":"Simple and inexpensive fluorescence-based technique for high-throughput antimalarial drug screening","volume":"48","author":"M Smilkstein","year":"2004","journal-title":"Antimicrob Agents Chemother"},{"issue":"7296","key":"ppat.1011517.ref022","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1038\/nature09107","article-title":"Thousands of chemical starting points for antimalarial lead identification","volume":"465","author":"FJ Gamo","year":"2010","journal-title":"Nature"},{"issue":"2","key":"ppat.1011517.ref023","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s00436-017-5698-1","article-title":"Screening of chemical compound libraries identified new anti-Toxoplasma gondii agents","volume":"117","author":"OS Adeyemi","year":"2018","journal-title":"Parasitol Res"},{"issue":"2","key":"ppat.1011517.ref024","doi-asserted-by":"crossref","first-page":"e01640","DOI":"10.1128\/AAC.01640-17","article-title":"Discovery of New Inhibitors of Toxoplasma gondii via the Pathogen Box","volume":"62","author":"J Spalenka","year":"2018","journal-title":"Antimicrob Agents Chemother"},{"issue":"12","key":"ppat.1011517.ref025","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1016\/j.chembiol.2011.09.016","article-title":"Identification and validation of tetracyclic benzothiazepines as Plasmodium falciparum cytochrome bc1 inhibitors","volume":"18","author":"CK Dong","year":"2011","journal-title":"Chem Biol"},{"issue":"2","key":"ppat.1011517.ref026","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.ijpddr.2018.04.007","article-title":"Functional screening of selective mitochondrial inhibitors of Plasmodium","volume":"8","author":"MG Gomez-Lorenzo","year":"2018","journal-title":"Int J Parasitol Drugs Drug Resist"},{"key":"ppat.1011517.ref027","doi-asserted-by":"crossref","first-page":"e38131","DOI":"10.7554\/eLife.38131","article-title":"Elucidating the mitochondrial proteome of Toxoplasma gondii reveals the presence of a divergent cytochrome c oxidase","volume":"7","author":"A Seidi","year":"2018","journal-title":"eLife"},{"issue":"1","key":"ppat.1011517.ref028","doi-asserted-by":"crossref","first-page":"e4288","DOI":"10.21769\/BioProtoc.4288","article-title":"Real-time analysis of mitochondrial electron transport chain function in Toxoplasma gondii parasites using a Seahorse XFe96 extracellular flux analyzer","volume":"12","author":"JA Hayward","year":"2022","journal-title":"Bio-protocol"},{"issue":"2","key":"ppat.1011517.ref029","doi-asserted-by":"crossref","first-page":"e1009211","DOI":"10.1371\/journal.ppat.1009211","article-title":"Divergent features of the coenzyme Q:cytochrome c oxidoreductase complex in Toxoplasma gondii parasites","volume":"17","author":"JA Hayward","year":"2021","journal-title":"PLoS Pathog"},{"issue":"7","key":"ppat.1011517.ref030","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1002\/ps.520","article-title":"The strobilurin fungicides","volume":"58","author":"DW Bartlett","year":"2002","journal-title":"Pest Manag Sci"},{"issue":"10","key":"ppat.1011517.ref031","doi-asserted-by":"crossref","first-page":"e1805","DOI":"10.1371\/journal.pntd.0001805","article-title":"Agrochemicals against malaria, sleeping sickness, leishmaniasis and Chagas disease","volume":"6","author":"M Witschel","year":"2012","journal-title":"PLoS Negl Trop Dis"},{"issue":"8","key":"ppat.1011517.ref032","doi-asserted-by":"crossref","first-page":"e71726","DOI":"10.1371\/journal.pone.0071726","article-title":"Reconstructing the Qo site of Plasmodium falciparum bc 1 complex in the yeast enzyme","volume":"8","author":"C Vallieres","year":"2013","journal-title":"PLoS One"},{"issue":"1","key":"ppat.1011517.ref033","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1021\/ml400315s","article-title":"Potent and selective inhibitors of CDPK1 from T. gondii and C. parvum based on a 5-aminopyrazole-4-carboxamide scaffold","volume":"5","author":"Z Zhang","year":"2014","journal-title":"ACS Med Chem Lett"},{"issue":"12","key":"ppat.1011517.ref034","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1021\/acsmedchemlett.5b00319","article-title":"SAR Studies of 5-Aminopyrazole-4-carboxamide Analogues as Potent and Selective Inhibitors of Toxoplasma gondii CDPK1","volume":"6","author":"W Huang","year":"2015","journal-title":"ACS Med Chem Lett"},{"issue":"1","key":"ppat.1011517.ref035","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s12936-019-2642-0","article-title":"Application of the automated haematology analyzer XN-30 for discovery and development of anti-malarial drugs","volume":"18","author":"T Tougan","year":"2019","journal-title":"Malar J"},{"issue":"5","key":"ppat.1011517.ref036","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1093\/rheumatology\/36.5.560","article-title":"Auranofin","volume":"36","author":"WF Kean","year":"1997","journal-title":"Br J Rheumatol"},{"key":"ppat.1011517.ref037","doi-asserted-by":"crossref","first-page":"618994","DOI":"10.3389\/fcimb.2021.618994","article-title":"Auranofin Resistance in Toxoplasma gondii Decreases the Accumulation of Reactive Oxygen Species but Does Not Target Parasite Thioredoxin Reductase","volume":"11","author":"CI Ma","year":"2021","journal-title":"Front Cell Infect Microbiol"},{"issue":"6","key":"ppat.1011517.ref038","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1016\/j.febslet.2008.02.028","article-title":"New uses for old drugs. Auranofin, a clinically established antiarthritic metallodrug, exhibits potent antimalarial effects in vitro: Mechanistic and pharmacological implications","volume":"582","author":"AR Sannella","year":"2008","journal-title":"FEBS Lett"},{"key":"ppat.1011517.ref039","doi-asserted-by":"crossref","first-page":"14455","DOI":"10.1038\/ncomms14455","article-title":"Cationic amino acid transporters play key roles in the survival and transmission of apicomplexan parasites","volume":"8","author":"E Rajendran","year":"2017","journal-title":"Nat Commun"},{"issue":"7296","key":"ppat.1011517.ref040","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/nature09022","article-title":"Calcium-dependent protein kinase 1 is an essential regulator of exocytosis in Toxoplasma","volume":"465","author":"S Lourido","year":"2010","journal-title":"Nature"},{"issue":"1","key":"ppat.1011517.ref041","doi-asserted-by":"crossref","first-page":"62","DOI":"10.4269\/ajtmh.1996.54.62","article-title":"Clinical studies of atovaquone, alone or in combination with other antimalarial drugs, for treatment of acute uncomplicated malaria in Thailand","volume":"54","author":"S Looareesuwan","year":"1996","journal-title":"Am J Trop Med Hyg"},{"issue":"8","key":"ppat.1011517.ref042","doi-asserted-by":"crossref","first-page":"4504","DOI":"10.1128\/AAC.02550-13","article-title":"Emergence of resistance to atovaquone-proguanil in malaria parasites: insights from computational modeling and clinical case reports","volume":"58","author":"G Cottrell","year":"2014","journal-title":"Antimicrob Agents Chemother"},{"issue":"2","key":"ppat.1011517.ref043","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/S0166-6851(99)00148-6","article-title":"Mutations in the cytochrome b gene of Plasmodium berghei conferring resistance to atovaquone","volume":"104","author":"D Syafruddin","year":"1999","journal-title":"Mol Biochem Parasitol"},{"issue":"2","key":"ppat.1011517.ref044","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.01866-16","article-title":"Genetic Evidence for Cytochrome b Qi Site Inhibition by 4(1H)-Quinolone-3-Diarylethers and Antimycin in Toxoplasma gondii","volume":"61","author":"PH Alday","year":"2017","journal-title":"Antimicrob Agents Chemother"},{"issue":"11","key":"ppat.1011517.ref045","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1021\/acsinfecdis.8b00133","article-title":"Targeted Structure-Activity Analysis of Endochin-like Quinolones Reveals Potent Qi and Qo Site Inhibitors of Toxoplasma gondii and Plasmodium falciparum Cytochrome bc1 and Identifies ELQ-400 as a Remarkably Effective Compound against Acute Experimental Toxoplasmosis","volume":"4","author":"EV McConnell","year":"2018","journal-title":"ACS Infect Dis"},{"issue":"2\u20133","key":"ppat.1011517.ref046","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/S0014-5793(00)01082-6","article-title":"The effect of reactive oxygen species generated from the mitochondrial electron transport chain on the cytochrome c oxidase activity and on the cardiolipin content in bovine heart submitochondrial particles","volume":"466","author":"G Paradies","year":"2000","journal-title":"FEBS Lett"},{"issue":"4","key":"ppat.1011517.ref047","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1128\/AAC.00895-06","article-title":"Growth inhibition of Toxoplasma gondii and Plasmodium falciparum by nanomolar concentrations of 1-hydroxy-2-dodecyl-4(1H)quinolone, a high-affinity inhibitor of alternative (type II) NADH dehydrogenases","volume":"51","author":"A Saleh","year":"2007","journal-title":"Antimicrob Agents Chemother"},{"issue":"7","key":"ppat.1011517.ref048","doi-asserted-by":"crossref","first-page":"3739","DOI":"10.1128\/AAC.00486-12","article-title":"HDQ, a potent inhibitor of Plasmodium falciparum proliferation, binds to the quinone reduction site of the cytochrome bc1 complex","volume":"56","author":"C Vallieres","year":"2012","journal-title":"Antimicrob Agents Chemother"},{"issue":"1","key":"ppat.1011517.ref049","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.molbiopara.2013.05.008","article-title":"Identification of dihydroorotate dehydrogenase as a relevant drug target for 1-hydroxyquinolones in Toxoplasma gondii","volume":"190","author":"J Hegewald","year":"2013","journal-title":"Mol Biochem Parasitol"},{"issue":"4","key":"ppat.1011517.ref050","doi-asserted-by":"crossref","first-page":"e0214023","DOI":"10.1371\/journal.pone.0214023","article-title":"Mitochondrial type II NADH dehydrogenase of Plasmodium falciparum (PfNDH2) is dispensable in the asexual blood stages","volume":"14","author":"H Ke","year":"2019","journal-title":"PLoS One"},{"issue":"8","key":"ppat.1011517.ref051","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1007\/s00417-010-1379-9","article-title":"Does atovaquone prolong the disease-free interval of toxoplasmic retinochoroiditis?","volume":"248","author":"S Winterhalter","year":"2010","journal-title":"Graefes Arch Clin Exp Ophthalmol"},{"issue":"9","key":"ppat.1011517.ref052","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1086\/339551","article-title":"Randomized phase II trial of atovaquone with pyrimethamine or sulfadiazine for treatment of toxoplasmic encephalitis in patients with acquired immunodeficiency syndrome: ACTG 237\/ANRS 039 Study. AIDS Clinical Trials Group 237\/Agence Nationale de Recherche sur le SIDA, Essai 039","volume":"34","author":"K Chirgwin","year":"2002","journal-title":"Clin Infect Dis"},{"issue":"3","key":"ppat.1011517.ref053","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1080\/09273940600659740","article-title":"Reactivation of Toxoplasma retinochoroiditis under atovaquone therapy in an immunocompetent patient","volume":"14","author":"H Baatz","year":"2006","journal-title":"Ocul Immunol Inflamm"},{"issue":"1","key":"ppat.1011517.ref054","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1017\/S0031182000049003","article-title":"Novel anti-malarial hydroxynaphthoquinones with potent broad spectrum anti-protozoal activity","volume":"90","author":"AT Hudson","year":"1985","journal-title":"Parasitology"},{"issue":"7","key":"ppat.1011517.ref055","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1093\/infdis\/jiu565","article-title":"Diversity-oriented synthesis probe targets Plasmodium falciparum cytochrome b ubiquinone reduction site and synergizes with oxidation site inhibitors","volume":"211","author":"AK Lukens","year":"2015","journal-title":"J Infect Dis"},{"issue":"8","key":"ppat.1011517.ref056","doi-asserted-by":"crossref","first-page":"2100","DOI":"10.1128\/AAC.44.8.2100-2108.2000","article-title":"Mutations in Plasmodium falciparum cytochrome b that are associated with atovaquone resistance are located at a putative drug-binding site","volume":"44","author":"M Korsinczky","year":"2000","journal-title":"Antimicrob Agents Chemother"},{"issue":"11","key":"ppat.1011517.ref057","doi-asserted-by":"crossref","first-page":"e01053","DOI":"10.1128\/AAC.01053-18","article-title":"Screening the Pathogen Box for Molecules Active against Plasmodium Sexual Stages Using a New Nanoluciferase-Based Transgenic Line of P. berghei Identifies Transmission-Blocking Compounds","volume":"62","author":"J Calit","year":"2018","journal-title":"Antimicrob Agents Chemother"},{"issue":"4","key":"ppat.1011517.ref058","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/S0092-8674(04)00449-0","article-title":"Calcium and a calcium-dependent protein kinase regulate gamete formation and mosquito transmission in a malaria parasite","volume":"117","author":"O Billker","year":"2004","journal-title":"Cell"},{"issue":"3","key":"ppat.1011517.ref059","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1093\/jb\/mvs058","article-title":"Critical roles of the mitochondrial complex II in oocyst formation of rodent malaria parasite Plasmodium berghei","volume":"152","author":"A Hino","year":"2012","journal-title":"J Biochem"},{"issue":"3","key":"ppat.1011517.ref060","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.immuni.2008.07.012","article-title":"Dynamics of neutrophil migration in lymph nodes during infection","volume":"29","author":"T Chtanova","year":"2008","journal-title":"Immunity"},{"issue":"3","key":"ppat.1011517.ref061","doi-asserted-by":"crossref","first-page":"e01114","DOI":"10.1128\/mBio.01114-14","article-title":"Efficient gene disruption in diverse strains of Toxoplasma gondii using CRISPR\/CAS9","volume":"5","author":"B Shen","year":"2014","journal-title":"MBio"},{"key":"ppat.1011517.ref062","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1016\/B978-0-12-815041-2.00020-7","volume-title":"Toxoplasma gondii the model apicomplexan\u2014perspectives and methods.","author":"S. Jacot DL","year":"2020"},{"issue":"8","key":"ppat.1011517.ref063","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1021\/ml400180d","article-title":"Structural modification of pantothenamides counteracts degradation by pantetheinase and improves antiplasmodial activity","volume":"4","author":"M de Villiers","year":"2013","journal-title":"ACS Med Chem Lett"},{"issue":"1","key":"ppat.1011517.ref064","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.molbiopara.2009.09.005","article-title":"Plasmodium falciparum culture: the benefits of shaking","volume":"169","author":"RJ Allen","year":"2010","journal-title":"Mol Biochem Parasitol"},{"issue":"6283","key":"ppat.1011517.ref065","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1126\/science.aad9279","article-title":"Parasites resistant to the antimalarial atovaquone fail to transmit by mosquitoes","volume":"352","author":"CD Goodman","year":"2016","journal-title":"Science"},{"key":"ppat.1011517.ref066","doi-asserted-by":"crossref","first-page":"37502","DOI":"10.1038\/srep37502","article-title":"Identification of inhibitors that dually target the new permeability pathway and dihydroorotate dehydrogenase in the blood stage of Plasmodium falciparum","volume":"6","author":"BK Dickerman","year":"2016","journal-title":"Sci Rep"},{"issue":"2","key":"ppat.1011517.ref067","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1177\/108705719900400206","article-title":"A Simple Statistical Parameter for Use in Evaluation and Validation of High Throughput Screening Assays","volume":"4","author":"JH Zhang","year":"1999","journal-title":"J Biomol Screen"},{"issue":"12","key":"ppat.1011517.ref068","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1021\/acsinfecdis.6b00101","article-title":"A Novel Methodology for Bioenergetic Analysis of Plasmodium falciparum Reveals a Glucose-Regulated Metabolic Shift and Enables Mode of Action Analyses of Mitochondrial Inhibitors","volume":"2","author":"T Sakata-Kato","year":"2016","journal-title":"ACS Infect Dis"},{"issue":"2","key":"ppat.1011517.ref069","doi-asserted-by":"crossref","first-page":"e54974","DOI":"10.1371\/journal.pone.0054974","article-title":"Pantothenamides are potent, on-target inhibitors of Plasmodium falciparum growth when serum pantetheinase is inactivated","volume":"8","author":"C Spry","year":"2013","journal-title":"PLoS One"},{"issue":"6","key":"ppat.1011517.ref070","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1038\/nprot.2012.058","article-title":"Assessment of mitochondrial respiratory chain enzymatic activities on tissues and cultured cells","volume":"7","author":"M Spinazzi","year":"2012","journal-title":"Nat Protoc"},{"issue":"2","key":"ppat.1011517.ref071","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.molbiopara.2004.04.004","article-title":"Synchronous invasion of host cells by Toxoplasma gondii","volume":"136","author":"BF Kafsack","year":"2004","journal-title":"Mol Biochem Parasitol"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1011987","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000}},{"DOI":"10.1371\/journal.ppat.1011517","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T00:00:00Z","timestamp":1691107200000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1011517","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T13:38:27Z","timestamp":1691156307000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1011517"}},"subtitle":[],"editor":[{"given":"Dominique","family":"Soldati-Favre","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,7,20]]},"references-count":71,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,7,20]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1011517","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2022.02.13.480284","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,20]]}}}