Theileria annulata Hijacks Host Signaling: Integrated Phosphoproteomics and transcriptomics Unveils ERK1/2 as a Central Regulator of Host Transcription Factors

This study elucidates Theileria annulata’s manipulation of host cell signaling using phosphoproteomic and transcriptomic approaches. We unveil the parasite's control over multiple cellular processes, including apoptosis, calcium/calmodulin-dependent protein kinase (CAMK) regulation, and telomere maintenance. A central finding of our study is the parasite's targeted manipulation of the ERK1/2 pathway, a key regulator of cellular proliferation and survival. By orchestrating the phosphorylation of essential transcription factors, T. annulata ensures its persistence within the host cell. Importantly, our data demonstrate that pharmacological inhibition of ERK signaling triggers apoptosis in infected cells, establishing this pathway as a promising therapeutic target. Beyond host manipulation, we characterize parasite phosphoproteins and transcription factors, revealing insights into Theileria's complex lifecycle and adaptive mechanisms. These findings collectively contribute to a more comprehensive understanding of the Theileria -host interaction, paving the way for the development of innovative therapeutic interventions to combat this economically significant disease.