A novel anti-Toxoplasma peptide suppresses parasite invasion and rescues host autophagic defenses.

Toxoplasma gondii, a ubiquitous intracellular protozoan parasite, poses life-threatening risks to immunocompromised hosts. Current first-line treatments for toxoplasmosis are limited by significant toxicity and high post-treatment recurrence rates. In this study, we employed phage display technology to identify peptides targeting TgMIC6 and disrupting its immune evasion function. Among these, the C8 peptide exhibited dual efficacy: it not only inhibited T. gondii invasion in vitro but also restored host autophagy, countering the parasite's immune escape mechanisms. Furthermore, in vivo studies confirmed the potent parasiticidal activity of C8 against multiple T. gondii strains. These findings highlight C8 as a promising therapeutic candidate for toxoplasmosis.IMPORTANCEThe study identifies the C8 peptide as a novel anti-Toxoplasma agent with dual efficacy: it directly inhibits parasite invasion and restores host autophagy compromised by T. gondii immune evasion. Demonstrating potent parasiticidal activity in vitro and in vivo, C8 significantly prolongs survival in acute infection models across multiple strains without cytotoxicity. Its multi-target mechanism and favorable safety profile address critical limitations of current therapies. While stability and chronic infection efficacy require optimization, C8 represents a promising peptide-based therapeutic candidate, offering a foundation for developing next-generation anti-toxoplasmosis drugs with enhanced specificity and reduced side effects. This work highlights the potential of peptide biologics in combating apicomplexan infections.