Host Sialic Acids: A Delicacy for the Pathogen with Discerning Taste

Sialic acids (neuraminic acids) are a diverse family of nine carbon (nonulosonic) α-keto acidic carbohydrates. The canonical sialic acid, 2-keto-3-deoxy-5-acetamido-D-glycero-D-galacto-nonulosonic acid, also known as N-acetylneuraminic acid (Neu5Ac) is the backbone on which a large number of known modifications are made ( 1 ). The Neu5Ac structure is typified by a 6-carbon carboxylic acid ring structure with a glycerol tail, an acetamido at the C-5 position and hydroxyl groups present on C-4, C-7, C-8, and C-9. Modifications occur primarily on the hydroxyl groups, with O-acetylation being the most common alteration, and substitutions have been shown to occur after the completion of the core structure ( 2 ). Other modifications such as O-methylation, O-lactylation, and O-sulfation add to the diversity of this molecule in vivo. Two structurally similar sialic acids, N-glycolylneuraminic acid (Neu5Gc), which differs from Neu5Ac by the presence of a hydroxyl group on the N-5 acetyl moiety, and 2-keto-3-deoxyl-D-glycero-D-galacto-nonulosonic acid (KDN), a deaminated form of Neu5Ac, also occur in nature and similar modifications are made to their core structure ( 1 ). These three main structures (Neu5Ac, Neu5Gc, and KDN) encompass the family of sialic acids due to their retention of the same stereochemical configuration of the 9-carbon backbone.