Stress-responsive Entamoeba topoisomerase II: a potential antiamoebic target

Abstract

Topoisomerases, the ubiquitous enzymes involved in all DNA processes across the biological world, are targets for various anticancer and antimicrobial agents. In Entamoeba histolytica, the causative agent of amebiasis, we found one of seven unexplored putative topoisomerases to be highly upregulated during heat shock and oxidative stress, and also during the late hours of encystation. Further analysis revealed the upregulated enzyme to be a eukaryotic type IIA topoisomerase (TopoII) with demonstrable activity in vitro. This enzyme is localized to newly forming nuclei during encystation. Gene silencing of the TopoII reduces viability and encystation efficiency. Notable susceptibility of Entamoeba TopoII to prokaryotic topoisomerase inhibitors opens up the possibility for exploring this enzyme as a new antiamoebic target.