Schematic of <i>Entamoeba histolytica</i> activities leading to mucus layer depletion and invasion of the human colon.

<p>During its vegetative life style (A), <i>E. histolytica</i> exploits lipids (from lipid-rich food particles, bacteria, and shed epithelial cells) and carbohydrates (undigested glycan-rich food particles provided by the bolus or shed mucus fragment) present in the colonic environment. (B) When dietary polysaccharides are scarce, we hypothesize that <i>E. histolytica</i> turns to host mucus by first deploying a set of polysaccharide hydrolases that depletes the protective oligosaccharide side chains of mucin which can be then targeted by cysteine proteases leading to the depletion of the protective mucus barrier and allowing subsequent invasion of the mucosa. This adaptive foraging could reflect the coevolved functional versatility of <i>E. histolytica</i> glycobiome and the structural diversity of host mucus glycans involved in the interaction.