The Entamoeba histolytica serum-inducible transmembrane kinase EhTMKB1-9 is involved in intestinal amebiasis

Abstract

Entamoeba histolytica possesses a family of approximately 100 putative transmembrane kinases (TMKs), indicating that the parasite has an extensive means of environmental sensing. The TMKs have been divided into nine sub-groups based on the sequence composition of their intracellular kinase as well as extracellular cysteine-rich domains. EhTMKB1-9 has been recently shown to be expressed in proliferating trophozoites and induced by serum. Interference with EhTMKB1-9 by antisense RNA knockdown or expression of a truncated protein diminished proliferation, adhesion and cytotoxicity. Here we report the involvement of EhTMKB1-9 in phagocytosis and its virulence function in the formation of amebic colitis. Trophozoites induced to express higher levels of wild type EhTMKB1-9 showed increased capacity for endocytosis. In contrast, cells compromised for the EhTMKB1-9 expression through antisense inhibition showed significantly lower levels of phagocytosis and endocytosis under the experimental conditions. The role of EhTMKB1-9 as a virulence factor was studied using animal models of amebiasis. Trophozoites expressing high levels of mutant protein lacking the kinase domain showed a competitive disadvantage with regard to survival as well as invasive phenotype in the murine model of amebic colitis. The same parasites however, were not compromised in their ability to generate abscess in the gerbil model of invasive liver amebiasis. EhTMKB1-9 is the second member from the "B" group of EhTMKs which seems to be deployed by the parasite during intestinal infection. TMKs are attractive targets for drug development because of their requirement in virulence and proliferation.