# Trypanosoma cruzi P21 Is a Pleiotropic Protein That Is Involved in Parasite Host Cell Invasion and Intracellular Parasitism

## TL;DR

This study shows that the P21 protein in the T. cruzi parasite is crucial for invading host cells and causing infection, especially in a low-virulence strain.

## Contribution

The study reveals that P21 is a pleiotropic protein with strain-specific roles in T. cruzi infection, particularly in the G strain.

## Key findings

- P21 knockout reduces parasite invasion and multiplication in Vero cells.
- P21 deficiency leads to reduced heart tissue parasitism in mice.
- P21 influences egress and persistence in the G strain differently than in the Y strain.

## Abstract

We characterized the secreted Trypanosoma cruzi P21 protein and hypothesized its role in parasite invasion and multiplication. To investigate the role of T. cruzi P21 protein in host‐parasite interactions, specifically focusing on the low‐virulence G strain. P21 knockout parasites were generated using CRISPR/Cas9. Cell invasion, multiplication, egress, and tissue parasitism were assessed in vitro and in vivo, comparing knockout and control parasites. P21 knockout significantly reduced parasite invasion and multiplication in Vero cells. In vivo, knockout parasites also showed reduced heart tissue parasitism in infected mice, despite no observable systemic parasitemia. Accordingly, P21 knockout trypomastigote egress was reduced in Vero cells. P21 plays a pleiotropic role in T. cruzi infection, differentially impacting parasite biology in the low‐virulent G strain. In the G strain, P21 promotes invasion and persistence, potentially through mechanisms distinct from its role in the Y strain previously described. This highlights its potential as a therapeutic target for Chagas disease, warranting further investigation into strain‐specific functions.

This study reveals the pleiotropic role of Trypanosoma cruzi P21 protein in the low‐virulence G strain. P21 knockout significantly impairs parasite invasion, intracellular multiplication, and egress in vitro. In vivo, P21 deficiency leads to reduced cardiac tissue parasitism, suggesting its role in establishing and maintaining silent infections. P21 influences parasite persistence and host‐pathogen interactions, highlighting its potential as a therapeutic target with strain‐specific implications.