{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:15:21Z","timestamp":1791296121686,"version":"4.1.0"},"reference-count":43,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T00:00:00Z","timestamp":1456790400000},"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":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            New strategies targeting\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Plasmodium falciparum<\/jats:named-content>\n            gametocytes, the sexual-stage parasites that are responsible for malaria transmission, are needed to eradicate this disease. Most commonly used antimalarials are ineffective against\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. falciparum<\/jats:named-content>\n            gametocytes, allowing patients to continue to be infectious for over a week after asexual parasite clearance. A recent screen for gametocytocidal compounds demonstrated that the carboxylic polyether ionophore maduramicin is active at low nanomolar concentrations against\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. falciparum<\/jats:named-content>\n            sexual stages. In this study, we showed that maduramicin has an EC\n            <jats:sub>50<\/jats:sub>\n            (effective concentration that inhibits the signal by 50%) of 14.8 nM against late-stage gametocytes and significantly blocks\n            <jats:italic>in vivo<\/jats:italic>\n            transmission in a mouse model of malaria transmission. In contrast to other reported gametocytocidal agents, maduramicin acts rapidly\n            <jats:italic>in vitro<\/jats:italic>\n            , eliminating gametocytes and asexual schizonts in less than 12 h without affecting uninfected red blood cells (RBCs). Ring stage parasites are cleared by 24 h. Within an hour of drug treatment, 40% of the normally crescent-shaped gametocytes round up and become spherical. The number of round gametocytes increases to &gt;60% by 2 h, even before a change in membrane potential as monitored by MitoProbe DiIC1 (5) is detectable. Maduramicin is not preferentially taken up by gametocyte-infected RBCs compared to uninfected RBCs, suggesting that gametocytes are more sensitive to alterations in cation concentration than RBCs. Moreover, the addition of 15.6 nM maduramicin enhanced the gametocytocidal activity of the pyrazoleamide PA21A050, which is a promising new antimalarial candidate associated with an increase in intracellular Na\n            <jats:sup>+<\/jats:sup>\n            concentration that is proposed to be due to inhibition of PfATP4, a putative Na\n            <jats:sup>+<\/jats:sup>\n            pump. These results underscore the importance of cation homeostasis in sexual as well as asexual intraerythrocytic-stage\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. falciparum<\/jats:named-content>\n            parasites and the potential of targeting this pathway for drug development.\n          <\/jats:p>","DOI":"10.1128\/aac.01928-15","type":"journal-article","created":{"date-parts":[[2015,12,29]],"date-time":"2015-12-29T03:23:15Z","timestamp":1451359395000},"page":"1492-1499","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":29,"title":["Maduramicin Rapidly Eliminates Malaria Parasites and Potentiates the Gametocytocidal Activity of the Pyrazoleamide PA21A050"],"prefix":"10.1128","volume":"60","author":[{"given":"Maxim I.","family":"Maron","sequence":"first","affiliation":[{"name":"Department of Biology, Loyola University, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Crystal T.","family":"Magle","sequence":"additional","affiliation":[{"name":"Department of Biology, Loyola University, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beata","family":"Czesny","sequence":"additional","affiliation":[{"name":"Department of Biology, Loyola University, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin A.","family":"Turturice","sequence":"additional","affiliation":[{"name":"Department of Biology, Loyola University, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruili","family":"Huang","sequence":"additional","affiliation":[{"name":"National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zheng","sequence":"additional","affiliation":[{"name":"National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akhil B.","family":"Vaidya","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Center for Molecular Parasitology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim C.","family":"Williamson","sequence":"additional","affiliation":[{"name":"Department of Biology, Loyola University, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1314981"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1358\/dof.2008.33.12.1287737"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.mi.44.100190.002241"},{"key":"e_1_3_1_5_2","doi-asserted-by":"crossref","first-page":"976827","DOI":"10.1155\/2010\/976827","article-title":"The coming-out of malaria gametocytes","volume":"2010","author":"Kuehn A","year":"2010","unstructured":"Kuehn A, Pradel G. 2010. The coming-out of malaria gametocytes. J Biomed Biotechnol 2010:976827.","journal-title":"J Biomed Biotechnol"},{"key":"e_1_3_1_6_2","doi-asserted-by":"crossref","first-page":"3743","DOI":"10.1038\/srep03743","article-title":"Chemical signatures and new drug targets for gametocytocidal drug development","volume":"4","author":"Sun W","year":"2014","unstructured":"Sun W, Tanaka TQ, Magle CT, Huang W, Southall N, Huang R, Dehdashti SJ, McKew JC, Williamson KC, Zheng W. 2014. Chemical signatures and new drug targets for gametocytocidal drug development. Sci Rep 4:3743.","journal-title":"Sci Rep"},{"key":"e_1_3_1_7_2","doi-asserted-by":"crossref","first-page":"343","DOI":"10.7164\/antibiotics.36.343","article-title":"Novel polyether antibiotics X-14868A, B, C, and D produced by a Nocardia. Discovery, fermentation, biological as well as ionophore properties and taxonomy of the producing culture","volume":"36","author":"Liu C-M","year":"1983","unstructured":"Liu C-M, Hermann T, Downey A, Prosser BLT, Schildknecht E, Palleroni N, Westley J, Miller P. 1983. Novel polyether antibiotics X-14868A, B, C, and D produced by a Nocardia. Discovery, fermentation, biological as well as ionophore properties and taxonomy of the producing culture. J Antibiot 36:343\u2013350.","journal-title":"J Antibiot"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(86)90035-3"},{"key":"e_1_3_1_9_2","doi-asserted-by":"crossref","first-page":"447","DOI":"10.7164\/antibiotics.39.447","article-title":"Chemistry of maduramicin. I. Salt formation and normal ketalization","volume":"39","author":"Ellestad GA","year":"1986","unstructured":"Ellestad GA, Canfield N, Leese RA, Morton GO, James JC, Siegel MM, McGahren WJ. 1986. Chemistry of maduramicin. I. Salt formation and normal ketalization. J Antibiot (Tokyo) 39:447\u2013456.","journal-title":"J Antibiot (Tokyo)"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04332-14"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.3382\/ps.2010-00931"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2010.12.014"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4017(88)90013-1"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.45.070176.002441"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1645\/GE-783R.1"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1193225"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2012.12.006"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6521"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1414221111"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.12765"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01500-13"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0105817"},{"key":"e_1_3_1_23_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-12-408"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1315860"},{"key":"e_1_3_1_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.781840"},{"key":"e_1_3_1_26_2","doi-asserted-by":"publisher","DOI":"10.2307\/3280287"},{"key":"e_1_3_1_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01930-13"},{"key":"e_1_3_1_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep00118"},{"key":"e_1_3_1_29_2","doi-asserted-by":"publisher","DOI":"10.1124\/pr.58.3.10"},{"key":"e_1_3_1_30_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0115652"},{"key":"e_1_3_1_31_2","doi-asserted-by":"publisher","DOI":"10.1080\/02652039709374494"},{"key":"e_1_3_1_32_2","volume-title":"FOIA drug summaries\u2014NADA 139-075 CYGRO; 1% type A medicated article\u2014original approval","author":"US Food and Drug Administration","year":"2009","unstructured":"US Food and Drug Administration. 2009. FOIA drug summaries\u2014NADA 139-075 CYGRO; 1% type A medicated article\u2014original approval. US Food and Drug Adminstration, Washington, DC. http:\/\/www.fda.gov\/AnimalVeterinary\/Products\/ApprovedAnimalDrugProducts\/FOIADrugSummaries\/ucm111243.htm."},{"key":"e_1_3_1_33_2","doi-asserted-by":"publisher","DOI":"10.1136\/emj.2004.020883"},{"key":"e_1_3_1_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0020-7519(97)00079-9"},{"key":"e_1_3_1_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00212-06"},{"key":"e_1_3_1_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.9.3241-3245.2004"},{"key":"e_1_3_1_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/0020-7519(90)90056-S"},{"key":"e_1_3_1_38_2","doi-asserted-by":"crossref","first-page":"646534","DOI":"10.1155\/2012\/646534","article-title":"On programmed cell death in Plasmodium falciparum: status quo","volume":"2012","author":"Engelbrecht D","year":"2012","unstructured":"Engelbrecht D, Durand PM, Coetzer TL. 2012. On programmed cell death in Plasmodium falciparum: status quo. J Trop Med 2012:646534.","journal-title":"J Trop Med"},{"key":"e_1_3_1_39_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0060139"},{"key":"e_1_3_1_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00088-09"},{"key":"e_1_3_1_41_2","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12359"},{"key":"e_1_3_1_42_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0042107"},{"key":"e_1_3_1_43_2","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1042\/bj2740121","article-title":"Modification of host cell membrane lipid composition by the intra-erythrocytic human malaria parasite Plasmodium falciparum","volume":"274","author":"Hsiao LL","year":"1991","unstructured":"Hsiao LL, Howard RJ, Aikawa M, Taraschi TF. 1991. Modification of host cell membrane lipid composition by the intra-erythrocytic human malaria parasite Plasmodium falciparum. Biochem J 274(Part 1):121\u2013132.","journal-title":"Biochem J"},{"key":"e_1_3_1_44_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-1947"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01928-15","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01928-15","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:36:58Z","timestamp":1645475818000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.01928-15"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,3]]},"references-count":43,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2016,3]]}},"alternative-id":["10.1128\/AAC.01928-15"],"URL":"https:\/\/doi.org\/10.1128\/aac.01928-15","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,3]]},"assertion":[{"value":"2015-08-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-12-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-02-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}