BdCDPK5 is an essential regulator of Babesia divergens intraerythrocytic progression

Calcium-dependent protein kinases (CDPKs) are central regulators of developmental transitions in apicomplexan parasites, yet their roles in tick-borne pathogen Babesia remain largely uncharacterized. Using Babesia divergens , a zoonotic parasite of growing medical and veterinary concern, we identify BdCDPK5 as an essential enzyme controlling intraerythrocytic parasite replication. Through comprehensive transcriptional profiling of the bdcdpk repertoire across synchronized blood-stages, combined with an animal-free Ixodes ricinus membrane feeding infection model, we show that bdcdpk5 is dominantly expressed during vector tissue colonization and significantly upregulated upon erythrocyte invasion. Genetic disruption of BdCDPK5 caused long-term growth arrest and pronounced morphological defects, whereas its ectopic expression promoted parasite replication. Localization analyses further revealed BdCDPK5 to be diffusely distributed throughout the parasite cytoplasm and associated with vesicle-like structures within infected erythrocytes. Together, these findings establish BdCDPK5 as a molecular determinant of B. divergens intraerythrocytic infection and highlight it as a promising target for selective therapeutic intervention.