Authors

A Prajapati¹;  ¹ National Institute of Animal Biotechnology (NIAB), Hyderabad, Telangana, 500032, India

Discussion

Theileria annulata is a tick-transmitted apicomplexan parasite spread by Hyalomma spp. that infects bovine leukocytes and causes bovine tropical theileriosis (BTT), a disease responsible for annual economic losses exceeding US$1.3 billion in India. Distinct from most protozoan pathogens, T. annulata induces a reversible oncogenic transformation of infected B cells, macrophages, and dendritic cells, promoting sustained proliferation and resistance to apoptosis. This cancer-like phenotype highlights parasite encoded signalling pathways, particularly protein kinases, as attractive therapeutic targets. Building on previous kinome profiling that identified 54 protein kinases encoded by T. annulata, the present study focuses on the systematic characterization of cyclin-dependent kinases (CDKs) and their regulatory cyclins central orchestrators of cell cycle progression and transcriptional control. In-silico analyses resolved eight TaCDKs and four TaCyclins, and their transcriptional expression was validated by quantitative RT-PCR. Yeast two-hybrid assays demonstrated that individual TaCyclins interact with multiple TaCDKs, suggesting the assembly of flexible and potentially stage-specific regulatory complexes. Stage-resolved immunolocalization using affinity-purified polyclonal antibodies revealed distinct spatial distributions of TaCDKs and TaCyclins in schizont and merozoite stages. Furthermore, colocalization analyses during synchronized S and G2/M phases uncovered dynamic CDK-cyclin associations, implicating these complexes in coordinated regulation of parasite proliferation and host cell transformation. Together, these findings establish the first integrated functional framework of CDK-cyclin networks in T. annulata. By defining kinase modules that underpin parasite-driven cellular reprogramming, this study positions CDK-cyclin complexes as high-value molecular targets for selective kinase-based interventions and advances translational strategies to combat tropical theileriosis worldwide, highlighting their relevance for next-generation antiparasitic drug discovery, rational target prioritization, and development of host-directed therapeutic approaches capable of disrupting parasite persistence, limiting disease severity, and improving sustainable livestock health