Ribosomal Architecture and rRNA Modification Landscape in the Tick-Borne Parasite Babesia divergens.

Babesia is a tick-borne intracellular apicomplexan parasite responsible for diseases ranging from mild to fatal, with a broadening geographic distribution. Due to the complex life cycle of Babesia species, their survival depends on the precise control of gene expression, which is primarily regulated by epigenetic, transcriptional, and post-transcriptional mechanisms. High-resolution structural information on key components of the translation machinery, such as ribosomes, could aid in the development of antiparasitic drugs. Here, we report cryo-EM ribosome structures (2.6 Å) from the tick-borne apicomplexan pathogen Babesia divergens, showing associated tRNAs, an mRNA fragment, and RACK1, a signaling scaffold crucial to translation regulation. Density map analysis displays ribosome regions at atomic resolution (1.7 Å), which, when combined with nanopore sequencing, enabled the comprehensive identification of rRNA modifications, including modifications unreported in other organisms. The new rRNA modifications localize not only to the reduced Babesia rRNA expansion segments but also to functionally essential ribosomal sites, uncovering new avenues for therapeutic intervention against babesiosis.