Histone lactylation: a new epigenetic mark in the malaria parasite Plasmodium
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Epigenetic processes play important roles in the biology of the malaria parasite Plasmodium falciparum. Here, we characterised a new epigenetic mark, histone lactylation, for the first time in Plasmodium: it was found in two human malaria parasites, P. falciparum and P. knowlesi, and also in vivo in two rodent malaria models, P. yoelii and P. berghei. Histones were increasingly lactylated in response to elevated lactate levels in vitro and in vivo, 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 P. knowlesi than P. falciparum, suggesting that P. falciparum may have evolved particular epigenetic responses to this characteristic feature of its pathology. Finally, in the rodent model P. yoelii, hyperlactataemia correlated with parasite transcriptomic programmes that suggested metabolic ‘dormancy’.
Editor(s)
Greally, John M
Date Issued
2025-12-19
Date Acceptance
2025-12-12
Citation
PLoS Genetics, 2025, 21 (12)
ISSN
1553-7390
Publisher
Public Library of Science (PLoS)
Journal / Book Title
PLoS Genetics
Volume
21
Issue
12
Copyright Statement
© 2025 Jabre et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Subjects
Genetics & Heredity
Publication Status
Published
Article Number
e1011991
Date Publish Online
2025-12-19