Structural and functional characterization of sialic acid uptake and metabolism in pathogenic bacteria

Abstract

Sialic acids are nine-carbon sugar acids, which play an important role in a wide range of biological phenomena. Based on differences in its side chains there are approximately 50 isoforms of this sugar and N-acetylneuraminic acid (Neu5Ac) is the most common sialic acid. N-Glycolylneuraminic acid (Neu5Gc) is another common sialic acid, which differs from Neu5Ac by having an extra hydroxyl group at the fifth position. During evolution, the gene Cytidine Monophosphate-N-Acetylneuraminic acid Hydroxylase (CMAH) that converts Neu5Ac to Neu5Gc lost its activity in humans due to a frameshift mutation. Thus, humans have lost the ability to make Neu5Gc. In general, eukaryotic cells are surrounded by glycocalyx, a sugar jacket composed of proteoglycans, glycosphingolipids, and glycoproteins. Most of these glycans have sialic acid as their outermost sugar that helps in cell adhesion and signaling. Sialic acids serve as an interface between host and commensal or pathogenic microorganisms. In order to evade the host immune response, these bacteria have evolved to express sugars similar to their human host cells (1). During the process of infection, pathogenic bacteria, such as Haemophilus influenzae form communities that are termed biofilms, where these bacteria are intimately associated with each other on the exopolymer matrix. A study by Swords et al., shows that lipooligosaccharides (LOS) containing sialic acids promote biofilm formation of H. influenzae (2). Given the fact that there is dense array of sugars on the outside of the eukaryotic cells, many pathogenic and symbiotic bacteria have taken advantage of these sugars. Most of the pathogenic bacteria, including Fusobacterium nucleatum, Pasteurella multocida, and Vibrio cholera, that cause different diseases in humans and animals reside in mucus rich regions and scavenge sialic acids from the host. Further, these bacteria incorporate these sialic acids as the outermost sugars on their LOS/Lipopolysaccharide (LPS) and escape the host immune system via a process called ‘molecular mimicry’. In addition, a part of the scavenged sialic acids are utilized by pathogenic bacteria as carbon, nitrogen, and energy sources (3)(4).