How bacteria utilize sialic acid during interactions with the host: snip, snatch, dispatch, match and attach

Abstract

N -glycolylneuraminic acid (Neu5Gc), and its precursor N-acetylneuraminic acid (Neu5Ac), commonly referred to as sialic acids, are two of the most common glycans found in mammals. Humans carry a mutation in the enzyme that converts Neu5Ac into Neu5Gc, and as such, expression of Neu5Ac can be thought of as a ‘human specific’ trait. Bacteria can utilize sialic acids as a carbon and energy source and have evolved multiple ways to take up sialic acids. In order to generate free sialic acid, many bacteria produce sialidases that cleave sialic acid residues from complex glycan structures. In addition, sialidases allow escape from innate immune mechanisms, and can synergize with other virulence factors such as toxins. Human-adapted pathogens have evolved a preference for Neu5Ac, with many bacterial adhesins, and major classes of toxin, specifically recognizing Neu5Ac containing glycans as receptors. The preference of human-adapted pathogens for Neu5Ac also occurs during biosynthesis of surface structures such as lipo-oligosaccharide (LOS), lipo-polysaccharide (LPS) and polysaccharide capsules, subverting the human host immune system by mimicking the host. This review aims to provide an update on the advances made in understanding the role of sialic acid in bacteria-host interactions made in the last 5–10 years, and put these findings into context by highlighting key historical discoveries. We provide a particular focus on ‘molecular mimicry’ and incorporation of sialic acid onto the bacterial outer-surface, and the role of sialic acid as a receptor for bacterial adhesins and toxins.

Nutritional Interactions between Bacterial Species Colonising the Human Nasal Cavity: Current Knowledge and Future Prospects

“…Bacterial manipulation of sialylated eukaryotic receptors or secreted molecules has been recognised as an immune evasion strategy [43,[58][59][60]. The secreted sialidase NanA of Strep.…”

“…Sialic acid is either synthesised de novo or acquired from the human host. It is an energy source for bacteria but can also mimic sialylated molecules on the host cell surfaces to subvert the host immune response [58,60]. The Strep.…”

Bacterial neuraminidase inhibitory linarin from Dendranthema zawadskii

“…BNA also known as acyl-neuraminyl hydrolase cleaves terminal α-ketosidic linkage between N-acetylneuraminic acid and the adjacent sugar moieties such as oligosaccharides, polysaccharides, mucopolysaccharides, glycoproteins, and glycolipids [9]. Through these processes, the fragmented sialic acid enables entry of pathogens into the host to cause inflammation [10]. It can be a clue to control of biofilm formation and anti-inflammation effects by inhibition the activity of BNA.…”

Synthesis of Neuraminidase‐Resistant Sialyllactose Mimetics from N‐Acyl Mannosamines using Metabolically Engineered Escherichia coli

“…[2] On the other hand, it is a hallmark of several cancers and a target for pathogen infection. [3,4] Highly contagious viruses exploit the wide occurrence of sialylated structures in the human respiratory tract for infection. Influenza and coronaviruses, which represent two of the most important zoonotic threats, use sialic-acid-binding proteins present on their surface to target host cells.…”