Histone lactylation: A new epigenetic axis for host-parasite signalling in malaria?

Abstract

Epigenetic marks such as histone acetylation and methylation play important roles in the biology and virulence of malaria parasites. Here I report that histone lactylation is also found in these parasites, and speculate on its potential functions. Lactylation is a new epigenetic modification, discovered only in 2019 in human cells. This nascent field has since focussed largely on human biology, but lactyl epigenetic marks could be particularly important in malaria parasites, which are exposed to high and fluctuating lactate levels in their host environment. This is because parasites in the bloodstream respire by glycolysis, producing lactate, and hyperlactataemia is characteristic of severe malarial disease. Therefore, blood lactate could be a signal for the status of the infected host, which could be directly translated to virulence responses via histone lactylation and modulation of parasite gene expression. Responses could include the rate of conversion into sexual transmission stages, the expression of cytoadherence genes - which enhance immune evasion by the parasite but can exacerbate pathology in the host - and the modulation of parasite stress-resistance. Lactylation may soon join acetylation and methylation as a key tool in the epigenetic arsenal of Plasmodium.