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To sustain progress in disease control made in the last decade, new antimalarial therapies are needed to combat emerging drug resistance. Malaria parasites contain a relict chloroplast called the apicoplast, which harbors new targets for drug discovery. Unfortunately, some drugs targeting apicoplast pathways exhibit a delayed-death phenotype, which results in a slow onset-of-action that precludes their use as fast-acting, frontline therapies. Identification of druggable apicoplast biogenesis factors that will avoid the delayed-death phenotype is an important priority. Here, we find that chemical stabilization of an apicoplast-targeted mDHFR domain disrupts apicoplast biogenesis and inhibits parasite growth after a single lytic cycle, suggesting a non-delayed-death target. Our finding indicates that further interrogation of the mechanism-of-action of this exogenous fusion protein may reveal novel therapeutic avenues.<\/jats:p>","DOI":"10.1128\/msphere.00710-18","type":"journal-article","created":{"date-parts":[[2019,1,22]],"date-time":"2019-01-22T05:41:23Z","timestamp":1548135683000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":17,"title":["Disruption of Apicoplast Biogenesis by Chemical Stabilization of an Imported Protein Evades the Delayed-Death Phenotype in Malaria Parasites"],"prefix":"10.1128","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5725-7219","authenticated-orcid":false,"given":"Michael J.","family":"Boucher","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA"},{"name":"Department of Biochemistry, Stanford University School of Medicine, Stanford, 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