{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:40:46Z","timestamp":1791178846870,"version":"4.1.0"},"reference-count":47,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2014,9,1]],"date-time":"2014-09-01T00:00:00Z","timestamp":1409529600000},"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":[[2014,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Bis-thiazolium salts constitute a new class of antihematozoan drugs that inhibit parasite phosphatidylcholine biosynthesis. They specifically accumulate in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Plasmodium<\/jats:named-content>\n            - and\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Babesia<\/jats:named-content>\n            -infected red blood cells (IRBC). Here, we provide new insight into the choline analogue albitiazolium, which is currently being clinically tested against severe malaria. Concentration-dependent accumulation in\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            -infected erythrocytes reached steady state after 90 to 120 min and was massive throughout the blood cycle, with cellular accumulation ratios of up to 1,000. This could not occur through a lysosomotropic effect, and the extent did not depend on the food vacuole pH, which was the case for the weak base chloroquine. Analysis of albitiazolium accumulation in\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            IRBC revealed a high-affinity component that was restricted to mature stages and suppressed by pepstatin A treatment, and thus likely related to drug accumulation in the parasite food vacuole. Albitiazolium also accumulated in a second high-capacity component present throughout the blood cycle that was likely not related to the food vacuole and also observed with\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Babesia divergens<\/jats:named-content>\n            -infected erythrocytes. Accumulation was strictly glucose dependent, drastically inhibited by H\n            <jats:sup>+<\/jats:sup>\n            \/K\n            <jats:sup>+<\/jats:sup>\n            and Na\n            <jats:sup>+<\/jats:sup>\n            ionophores upon collapse of ionic gradients, and appeared to be energized by the proton-motive force across the erythrocyte plasma membrane, indicating the importance of transport steps for this permanently charged new type of antimalarial agent. This specific, massive, and irreversible accumulation allows albitiazolium to restrict its toxicity to hematozoa-infected erythrocytes. The intraparasitic compartmentation of albitiazolium corroborates a dual mechanism of action, which could make this new type of antimalarial agent resistant to parasite resistance.\n          <\/jats:p>","DOI":"10.1128\/aac.00040-14","type":"journal-article","created":{"date-parts":[[2014,7,8]],"date-time":"2014-07-08T04:16:33Z","timestamp":1404792993000},"page":"5519-5527","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":13,"title":["New Insight into the Mechanism of Accumulation and Intraerythrocytic Compartmentation of Albitiazolium, a New Type of Antimalarial"],"prefix":"10.1128","volume":"58","author":[{"given":"Sharon","family":"Wein","sequence":"first","affiliation":[{"name":"Dynamique des Interactions Membranaires Normales et Pathologiques, CNRS UMR 5235, Universit\u00e9 Montpellier 2, Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Tran Van Ba","sequence":"additional","affiliation":[{"name":"Dynamique des Interactions Membranaires Normales et Pathologiques, CNRS UMR 5235, Universit\u00e9 Montpellier 2, Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjorie","family":"Maynadier","sequence":"additional","affiliation":[{"name":"Dynamique des Interactions Membranaires Normales et Pathologiques, CNRS UMR 5235, Universit\u00e9 Montpellier 2, Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yann","family":"Bordat","sequence":"additional","affiliation":[{"name":"Dynamique des Interactions Membranaires Normales et Pathologiques, CNRS UMR 5235, Universit\u00e9 Montpellier 2, Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Perez","sequence":"additional","affiliation":[{"name":"Dynamique des Interactions Membranaires Normales et Pathologiques, CNRS UMR 5235, Universit\u00e9 Montpellier 2, Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Peyrottes","sequence":"additional","affiliation":[{"name":"Institut des Biomol\u00e9cules Max Mousseron, CNRS UMR 5247, Universit\u00e9 Montpellier 2, Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Fraisse","sequence":"additional","affiliation":[{"name":"Sanofi, TSU Infectious Diseases Unit, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henri J.","family":"Vial","sequence":"additional","affiliation":[{"name":"Dynamique des Interactions Membranaires Normales et Pathologiques, CNRS UMR 5235, Universit\u00e9 Montpellier 2, Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0808859"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2331"},{"key":"e_1_3_3_4_2","volume-title":"World malaria report 2011","author":"WHO","year":"2011","unstructured":"WHO. 2011. 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Plasmodium lipids: metabolism and function, p 327\u2013352. In ShermanIW (ed), Molecular approaches to malaria. ASM Press, Washington, DC."},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-6851(02)00281-5"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1550-7408.1982.tb04023.x"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2010.05.008"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.20347"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm9911027"},{"key":"e_1_3_3_14_2","first-page":"137","volume-title":"Drug discovery in infectious diseases","author":"Vial HJ","year":"2011","unstructured":"VialHJPenareteDWeinSCaldarelliSFraisseLPeyrottesS. 2011. Lipids as drug targets for malaria therapy, p 137\u2013162. In BeckerK (ed), Drug discovery in infectious diseases, vol 2. Apicomplexan parasites: molecular approaches toward targeted drug development. 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