Lactylation Dynamics in Myxozoan Proteins

Lactylation has recently emerged as a novel post-translational modification with critical implications for gene regulation and host–parasite interactions, as demonstrated for species of Plasmodium and Trypanosoma. Here, we applied an integrative approach combining in-silico and experimental analyses to detect protein lactylation in parasitic cnidarians in the class Myxozoa. In-silico analyses were conducted using data from seven myxozoan species, six obtained from public databases and one generated in this study. Experimental validation was based on Oxford Nanopore Technologies (ONT) genome sequencing and Western blotting of Myxobolus macroplasmodialis samples, a myxozoan parasite of the South American bryconid fish Salminus brasiliensis. This integrative approach enabled us to validate the in-silico analysis, to identify conserved lactylation sites in key stress-response proteins (including HSP70 and several metabolic enzymes), and to map electrochemical signatures of lactylation sites across the nanopore sequencing ONT dataset for M. macroplasmodialis. Comparative analyses across species demonstrated the predicted conserved regulatory roles and myxozoan species-specific variation in processes controlled by lactylation. Functional enrichment analyses further implicated lactylation in critical pathways, such as glycolysis, oxidative phosphorylation, and immune signaling, thus supporting its integration into core regulatory networks that underlie the functional biology of parasitism.