Dual Role of Entamoeba histolytica KERP2 in Regulating Gene Expression and Modulating Host Cell Function for Intestinal Colonization

Entamoeba histolytica , the protozoan parasite responsible for amoebiasis, deploys a complex array of virulence factors to establish infection and evade host defenses. Here, we identify KERP2 as a dual-function effector that regulates both parasite homeostasis and host cell remodeling. Bioinformatic analyses, cellular localization assays, and functional studies show that KERP2 localizes to the parasite nucleus, associates with chromatin, and modulates transcription, particularly regulating cysteine protease expression and sulfur metabolism. Concurrently, KERP2 is translocated into host epithelial cells, where it manipulates the G1/S transition, interacts with cytoskeletal regulators, and promotes actin remodeling, ultimately compromising epithelial barrier function. Our results elucidate how E. histolytica harnesses KERP2 to coordinate intracellular processes in the parasite while orchestrating pathogenic alterations in host cells. These insights shed light on a broader mechanism by which extracellular pathogens deploy multifunctional effectors to optimize virulence and adapt to diverse host environments, providing a valuable framework for studies on pathogen-host interactions beyond amoebiasis.