P21 Ablation Unveils Strain-Specific Transcriptional Reprogramming in Trypanosoma cruzi Amastigotes

Trypanosoma cruzi is the causative agent of Chagas disease and is capable of invading any nucleated cell in the vertebrate host. The parasite utilizes various virulence factors during cell invasion, including the P21 protein. P21 is encoded by a single-copy, nonconserved gene expressed across all T. cruzi life cycle stages. Its sequence codes for a protein implicated in cell invasion and parasite multiplication. Given the significant differences in biological behavior between distinct strains of T. cruzi, we ablated the P21-coding gene in two phylogenetically distant strains (G and Y strains) and assessed its impact on the transcriptome profile of intracellular amastigotes. Our findings revealed that P21 depletion affected the transcription of different genes in the G and Y strains, with each strain exhibiting enrichment for distinct biological processes. Notably, protein translation was the major biological process impacted by P21 depletion, showing upregulation in the G strain and downregulation in the Y strain. In conclusion, our findings demonstrate that P21 gene ablation induces strain-specific transcriptional reprogramming in T. cruzi amastigotes, revealing divergent roles for P21 in modulating fundamental cellular processes like protein translation and potentially influencing host-parasite interactions, contingent upon the parasite's genetic background.