{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T06:10:20Z","timestamp":1790230220203,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,5,23]],"date-time":"2016-05-23T00:00:00Z","timestamp":1463961600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003246","name":"Netherlands Organisation for Scientific Research","doi-asserted-by":"crossref","award":["NWO-VIDI 864.13.009"],"award-info":[{"award-number":["NWO-VIDI 864.13.009"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Max Planck Society and the European Community's Seventh Framework Program","award":["FP7\/2007;2013; Grant Agreement No. 242095"],"award-info":[{"award-number":["FP7\/2007;2013; Grant Agreement No. 242095"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Multidrug resistance (MDR) proteins belong to the B subfamily of the ATP Binding Cassette (ABC) transporters, which export a wide range of compounds including pharmaceuticals. In this study, we used reverse genetics to study the role of all seven <jats:italic>Plasmodium<\/jats:italic> MDR proteins during the life cycle of malaria parasites. Four <jats:italic>P. berghei<\/jats:italic> genes (encoding MDR1, 4, 6 and 7) were refractory to deletion, indicating a vital role during blood stage multiplication and validating them as potential targets for antimalarial drugs. Mutants lacking expression of MDR2, MDR3 and MDR5 were generated in both <jats:italic>P. berghei<\/jats:italic> and <jats:italic>P. falciparum<\/jats:italic>, indicating a dispensable role for blood stage development. Whereas <jats:italic>P. berghei<\/jats:italic> mutants lacking MDR3 and MDR5 had a reduced blood stage multiplication <jats:italic>in vivo<\/jats:italic>, blood stage growth of <jats:italic>P. falciparum<\/jats:italic> mutants <jats:italic>in vitro<\/jats:italic> was not significantly different. Oocyst maturation and sporozoite formation in <jats:italic>Plasmodium<\/jats:italic> mutants lacking MDR2 or MDR5 was reduced. Sporozoites of these <jats:italic>P. berghei<\/jats:italic> mutants were capable of infecting mice and life cycle completion, indicating the absence of vital roles during liver stage development. Our results demonstrate vital and dispensable roles of MDR proteins during blood stages and an important function in sporogony for MDR2 and MDR5 in both <jats:italic>Plasmodium<\/jats:italic> species.<\/jats:p>","DOI":"10.1111\/mmi.13373","type":"journal-article","created":{"date-parts":[[2016,3,19]],"date-time":"2016-03-19T01:13:46Z","timestamp":1458350026000},"page":"78-91","source":"Crossref","is-referenced-by-count":15,"title":["Vital and dispensable roles of <i>Plasmodium<\/i> multidrug resistance transporters during blood\u2010 and mosquito\u2010stage development"],"prefix":"10.1111","volume":"101","author":[{"given":"Sanna R.","family":"Rijpma","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology Radboud University Medical Center Geert\u2010Grooteplein 28 6525 GA Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten","family":"van der Velden","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Radboud University Medical Center Geert\u2010Grooteplein 28 6525 GA Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Annoura","sequence":"additional","affiliation":[{"name":"Department of Tropical Medicine The Jikei University School of Medicine Post code 105\u20108461 Nishi\u2010shinbashi 3\u201025\u20108 Minato\u2010ku Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim M.","family":"Matz","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology Radboud University Medical Center Geert\u2010Grooteplein 28 6525 GA Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanketha","family":"Kenthirapalan","sequence":"additional","affiliation":[{"name":"Parasitology Unit, Max Planck Institute for Infection Biology Charit\u00e9platz 1 10117 Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8547-7523","authenticated-orcid":false,"given":"Taco W. 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