Research Projects

Entamoeba histolytica is a global pathogen that causes intestinal and extraintestinal amebiasis in humans. Amoebic trophozoites have a strong migration ability, crossing the intestinal barrier to establish cellular niches in various organs. The lysosomotropic drug chloroquine has been used in treating invasive extraintestinal amoebiasis and malaria. Treatment with lysosomotropic agents like chloroquine, bafilomycin, concanamycin, and ammonium chloride has been found to decrease pinocytic, phagocytic, and trogocytic abilities in amoebic trophozoites. These agents are also effective against numerous cancers. Bafilomycin and concanamycin are selective inhibitors of V-ATPase, a proton pump responsible for ATP hydrolysis and proton translocation. Recent findings suggest that concanamycin and bafilomycin control the migration pattern in amoebic trophozoites. In higher eukaryotes, V1 domain subunits are implicated for binding cytoskeleton proteins and playing a role in cell migration. The proposed research will provide the first evidence that V-ATPase subunits directly regulate cell migration in E. histolytica. The V-ATPase pump is conserved throughout eukaryotes, improving understanding of cell migration in eukaryotes and contributing to designing amoebic V-ATPase-specific drugs or inhibitors for treating extraintestinal amoebiasis.