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

Abstract

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 inhibitedinvasionbut also restored host autophagy, countering the parasite's immune escape mechanisms. Furthermore,studies confirmed the potent parasiticidal activity of C8 against multiplestrains. These findings highlight C8 as a promising therapeutic candidate for toxoplasmosis.IMPORTANCEThe study identifies the C8 peptide as a novel anti-agent with dual efficacy: it directly inhibits parasite invasion and restores host autophagy compromised byimmune evasion. Demonstrating potent parasiticidal activityand, 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.