{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T08:22:09Z","timestamp":1790670129362,"version":"4.1.0"},"reference-count":68,"publisher":"American Society for Microbiology","license":[{"start":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T00:00:00Z","timestamp":1690243200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T00:00:00Z","timestamp":1690243200000},"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":["mBio"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    For its replication within red blood cells, the malaria parasite depends on a highly active and regulated lipid metabolism. Enzymes involved in lipid metabolic processes such as phospholipases are, therefore, potential drug targets. Here, using reverse genetics approaches, we show that only 1 out of the 19 putative phospholipases expressed in asexual blood stages of\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    is essential for proliferation\n                    <jats:italic>in vitro<\/jats:italic>\n                    , pointing toward a high level of redundancy among members of this enzyme family. Using conditional mislocalization and gene disruption techniques, we show that this essential phosphoinositide-specific phospholipase C (PI-PLC, PF3D7_1013500) has a previously unrecognized essential role during intracellular parasite maturation, long before its previously perceived role in parasite egress and invasion. Subsequent lipidomic analysis suggests that PI-PLC mediates cleavage of phosphatidylinositol bisphosphate (PIP\n                    <jats:sub>2<\/jats:sub>\n                    ) in schizont-stage parasites, underlining its critical role in regulating phosphoinositide levels in the parasite.\n                  <\/jats:p>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      The clinical symptoms of malaria arise due to repeated rounds of replication of\n                      <jats:italic>Plasmodium<\/jats:italic>\n                      parasites within red blood cells (RBCs). Central to this is an intense period of membrane biogenesis. Generation of membranes not only requires\n                      <jats:italic>de novo<\/jats:italic>\n                      synthesis and acquisition but also the degradation of phospholipids, a function that is performed by phospholipases. In this study, we investigate the essentiality of the 19 putative phospholipase enzymes that the human malaria parasite\n                      <jats:italic>Plasmodium falciparum<\/jats:italic>\n                      expresses during its replication within RBCs. We not only show that a high level of functional redundancy exists among these enzymes but, at the same time, also identify an essential role for the phosphoinositide-specific phospholipase C in parasite development and cleavage of the phospholipid phosphatidylinositol bisphosphate.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.01413-23","type":"journal-article","created":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T09:00:29Z","timestamp":1690275629000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":10,"title":["Global analysis of putative phospholipases in\n                    <i>Plasmodium falciparum<\/i>\n                    reveals an essential role of the phosphoinositide-specific phospholipase C in parasite 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Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehar Nihal","family":"Singh","sequence":"additional","affiliation":[{"name":"Malaria Biochemistry Laboratory, The Francis Crick Institute , London, United Kingdom"},{"name":"Division of Infection and Immunity, University College London , London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6208-791X","authenticated-orcid":true,"given":"Jan","family":"Strauss","sequence":"additional","affiliation":[{"name":"Centre for Structural Systems Biology , Hamburg, Germany"},{"name":"Bernhard Nocht Institute for Tropical Medicine , Hamburg, Germany"},{"name":"University of Hamburg , Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Sait","sequence":"additional","affiliation":[{"name":"Electron Microscopy Science Technology Platform, The Francis Crick Institute , London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0260-613X","authenticated-orcid":true,"given":"Lucy M.","family":"Collinson","sequence":"additional","affiliation":[{"name":"Electron Microscopy Science Technology Platform, The Francis Crick Institute , London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1379-9451","authenticated-orcid":true,"given":"Dominik","family":"Schwudke","sequence":"additional","affiliation":[{"name":"Division of Bioanalytical Chemistry, Research Center Borstel, Leibniz Lung Center , Borstel, Germany"},{"name":"German Center for Infection Research, Thematic Translational Unit Tuberculosis, Partner Site Hamburg-L\u00fcbeck-Borstel-Riems , Borstel, Germany"},{"name":"German Center for Lung Research (DZL), Airway Research Center North (ARCN), Research Center Borstel, Leibniz Lung Center , Borstel, 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