Sweet impersonators: Molecular mimicry of host glycans by bacteria

Abstract

All bacteria display surface-exposed glycans that can play an important role in their interaction with the host and in select cases mimic the glycans found on host cells, an event called molecular or glycan mimicry. In this review, we highlight the key bacteria that display human glycan mimicry and provide an overview of the involved glycan structures. We also discuss the general trends and outstanding questions associated with human glycan mimicry by bacteria. Finally, we provide an overview of several techniques that have emerged from the discipline of chemical glycobiology, which can aid in the study of the composition, variability, interaction and functional role of these mimicking glycans.

Selective Exoenzymatic Labeling of Lipooligosaccharides of Neisseria gonorrhoeae with α2,6‐Sialoside Analogues

“…However, in case of host-microbe interactions, comprehending cell surface glycosylation and their biological functions extends not only to mammalian cells, but also to microbial glycans, as illustrated by the many glycan interactions between a host and microbe that influence processes like bacterial pathogenesis, interactions with host receptors, and sialylation to evade immune detection by mimicry of host glycans. [4,5] Currently, few glycoengineering techniques have been reported that can modify bacterial glycans. The most widely applied approach is metabolic oligosaccharide engineering (MOE), [6,7] which makes use of the cell's own metabolic pathways to incorporate monosaccharides with a chemical reporter group into sugar nucleotides that are eventually incorporated into bacterial glycans by native glycosyltransferases.…”

“…So far, many of the reported glycoengineering techniques have focused on mammalian cells and have contributed to a better understanding of the structure‐function relationship of glycans within the context of the glycocalyx. However, in case of host‐microbe interactions, comprehending cell surface glycosylation and their biological functions extends not only to mammalian cells, but also to microbial glycans, as illustrated by the many glycan interactions between a host and microbe that influence processes like bacterial pathogenesis, interactions with host receptors, and sialylation to evade immune detection by mimicry of host glycans [4,5] …”

“…Its lipooligosaccharides (LOS) contain a terminal N‐ acetyllactosamine, which can be α2,3‐sialylated by its native sialyltransferases that scavenge CMP‐sialic acid from the host [39,40] . The resulting sialylated terminal glycans on the bacterium resemble mammalian N‐ glycans and glycosphingolipids, and are thus a form of glycan mimicry that conceals the bacteria from immune detection [5] . The use of terminal sialic acids to display glycans that mimic the host extends to other pathogenic bacteria and raises questions about the role of this monosaccharide in the interaction with the immune system, making sialic acid on bacteria a prime target for glycoengineering [5] .…”

Synthetic Strategy towards a Carbocyclic N‐Acetylneuraminic Acid

“…The activity of sialidases directly impacts the level of sialic acid on cells, [4] allows the scavenging of sialic acid from other cells for use as an energy source [5] or is part of infection mechanisms of both viral and bacterial pathogens. [6] These various functions in health and disease, and the many different types of sialidases make this class of glycosidases an interesting target for study. The development of molecular tools that can perturb sialidase activity [7] and assist in their identification and quantification [8] is a key way to gain insight into their functional role(s).…”

“…Sialidases are the glycosyl hydrolase enzymes, also called glycosidases, responsible for cleaving sialic acids from the termini of glycans and are found in both vertebrates and various microbes. The activity of sialidases directly impacts the level of sialic acid on cells, [4] allows the scavenging of sialic acid from other cells for use as an energy source [5] or is part of infection mechanisms of both viral and bacterial pathogens [6] . These various functions in health and disease, and the many different types of sialidases make this class of glycosidases an interesting target for study.…”