{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:11:52Z","timestamp":1791227512039,"version":"4.1.0"},"reference-count":48,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2013,2,1]],"date-time":"2013-02-01T00:00:00Z","timestamp":1359676800000},"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":["Eukaryot Cell"],"published-print":{"date-parts":[[2013,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The antimalarial agent fosmidomycin is a validated inhibitor of the nonmevalonate isoprenoid biosynthesis (methylerythritol 4-phosphate [MEP]) pathway in the malaria parasite,\n            <jats:named-content content-type=\"genus-species\">Plasmodium falciparum<\/jats:named-content>\n            . Since multiple classes of prenyltransferase inhibitors kill\n            <jats:named-content content-type=\"genus-species\">P. falciparum<\/jats:named-content>\n            , we hypothesized that protein prenylation was one of the essential functions of this pathway. We found that MEP pathway inhibition with fosmidomycin reduces protein prenylation, confirming that\n            <jats:named-content content-type=\"genus-species\">de novo<\/jats:named-content>\n            isoprenoid biosynthesis produces the isoprenyl substrates for protein prenylation. One important group of prenylated proteins is small GTPases, such as Rab family members, which mediate cellular vesicular trafficking. We have found that Rab5 proteins dramatically mislocalize upon fosmidomycin treatment, consistent with a loss of protein prenylation. Fosmidomycin treatment caused marked defects in food vacuolar morphology and integrity, consistent with a defect in Rab-mediated vesicular trafficking. These results provide insights to the biological functions of isoprenoids in malaria parasites and may assist the rational selection of secondary agents that will be useful in combination therapy with new isoprenoid biosynthesis inhibitors.\n          <\/jats:p>","DOI":"10.1128\/ec.00073-12","type":"journal-article","created":{"date-parts":[[2012,12,8]],"date-time":"2012-12-08T08:19:09Z","timestamp":1354954749000},"page":"215-223","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":76,"title":["Isoprenoid Biosynthesis Inhibition Disrupts Rab5 Localization and Food Vacuolar Integrity in Plasmodium falciparum"],"prefix":"10.1128","volume":"12","author":[{"given":"Ruth","family":"Howe","sequence":"first","affiliation":[{"name":"Departments of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Kelly","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Jimah","sequence":"additional","affiliation":[{"name":"Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Hodge","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey R.","family":"Odom","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA"},{"name":"Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/415680a"},{"key":"e_1_3_3_3_2","volume-title":"World malaria report 2010","author":"Aregawi M","year":"2010","unstructured":"AregawiM CibulskisR KitaY OttenH WilliamsR World HealthOrganization. 2010. 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