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Here, we characterised a new epigenetic mark, histone lactylation, for the first time in\n                    <jats:italic>Plasmodium<\/jats:italic>\n                    : it was found in two human malaria parasites,\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    and\n                    <jats:italic>P. knowlesi<\/jats:italic>\n                    , and also\n                    <jats:italic>in vivo<\/jats:italic>\n                    in two rodent malaria models,\n                    <jats:italic>P. yoelii<\/jats:italic>\n                    and\n                    <jats:italic>P. berghei<\/jats:italic>\n                    . Histones were increasingly lactylated in response to elevated lactate levels\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    , making this mark uniquely well-placed to act as a metabolic sensor, since severe falciparum malaria characteristically leads to hyperlactataemia in the human host. Mass spectrometry showed that lysines on several parasite histones could be lactylated, as well as many non-histone chromatin proteins. Histone lactylation was less abundant and less inducible in\n                    <jats:italic>P. knowlesi<\/jats:italic>\n                    than\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    , suggesting that\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    may have evolved particular epigenetic responses to this characteristic feature of its pathology. Finally, in the rodent model\n                    <jats:italic>P. yoelii<\/jats:italic>\n                    , hyperlactataemia correlated with parasite transcriptomic programmes that suggested metabolic \u2018dormancy\u2019.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1011991","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T18:43:07Z","timestamp":1766169787000},"page":"e1011991","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Histone lactylation: A new epigenetic mark in the malaria parasite Plasmodium"],"prefix":"10.1371","volume":"21","author":[{"given":"Ibtissam","family":"Jabre","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nana 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