Role of fibronectin in the process of human intestinal cell disruption during E. histolytica infection

Abstract

Entamoeba histolytica is a protozoan that causes amoebiasis in humans which in extreme cases can result in death. One of the virulence factors of E. histolytica is cysteine proteinase which is involved with disruption, inflammation, and apoptosis of the intestinal cell layers. This disruption facilitates the amoeba's penetration into the vascular system and hence to metastasize into other organs. Cysteine proteinase blocks activity of several human proteins in the extracellular matrix, such as mucin-2, collagen, fibronectin, and laminin. Inhibition of several protein activities are predicted to lead the disruption of intestinal mucus, but the detailed mechanism is still unclear. We examined the mechanism using topology networks and functional analysis and the result showed links to 765 proteins, of which fibronectin was predominant in the network. Fibronectin interacts with ubiquitin conjugate, insulin-like factor binding protein-3, and integrin alpha chain-2 which play pivotal roles in maintaining cell cycle, survival, and apoptosis. Therefore, inhibition of the protein results in intestinal cells losing the ability to maintain homeostasis mechanism by which the disruption of intestinal cell occurs.

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