{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T18:40:20Z","timestamp":1792089620086,"version":"4.4.0"},"reference-count":16,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T00:00:00Z","timestamp":1594944000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T00:00:00Z","timestamp":1594944000000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T00:00:00Z","timestamp":1594944000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["Project Grant APP1106213"],"award-info":[{"award-number":["Project Grant APP1106213"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["Project Grant APP1162550"],"award-info":[{"award-number":["Project Grant APP1162550"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["Laureate Fellowship FL170100008"],"award-info":[{"award-number":["Laureate Fellowship FL170100008"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["CJ Maritn Felowship APP1072217"],"award-info":[{"award-number":["CJ Maritn Felowship APP1072217"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    The antibiotic actinonin kills malaria parasites (\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    ) by interfering with apicoplast function. Early evidence suggested that actinonin inhibited prokaryote-like post-translational modification in the apicoplast; mimicking its activity against bacteria. However, Amberg Johnson et al. (2017) identified the metalloprotease\n                    <jats:italic>Tg<\/jats:italic>\n                    FtsH1 as the target of actinonin in the related parasite\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    and implicated\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    FtsH1 as a likely target in malaria parasites. The authors were not, however, able to recover actinonin resistant malaria parasites, leaving the specific target of actinonin uncertain. We generated actinonin resistant\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    by in vitro selection and identified a specific sequence change in\n                    <jats:italic>Pf<\/jats:italic>\n                    FtsH1 associated with resistance. Introduction of this point mutation using CRISPr-Cas9 allelic replacement was sufficient to confer actinonin resistance in\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    . Our data unequivocally identify\n                    <jats:italic>Pf<\/jats:italic>\n                    FtsH1 as the target of actinonin and suggests that actinonin should not be included in the highly valuable collection of \u2018irresistible\u2019 drugs for combatting malaria.\n                  <\/jats:p>","DOI":"10.7554\/elife.58629","type":"journal-article","created":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T08:00:30Z","timestamp":1594972830000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.58629","source":"Crossref","is-referenced-by-count":10,"title":["A single point mutation in the Plasmodium falciparum FtsH1 metalloprotease confers actinonin resistance"],"prefix":"10.7554","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8923-7594","authenticated-orcid":true,"given":"Christopher D","family":"Goodman","sequence":"first","affiliation":[{"name":"School of BioSciences, University of Melbourne, Parkville, 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