Bacterial surfaces are rich in glycoconjugates that are mainly present in their outer layers and are of great importance for their interaction with the host innate immune system. The innate immune system is the first barrier against infection and recognizes pathogens via conserved pattern recognition receptors (PRRs). Lectins expressed by innate immune cells represent an important class of PRRs characterized by their ability to recognize carbohydrates. Among lectins in innate immunity, there are three major classes including the galectins, siglecs, and C-type lectin receptors. These lectins may contribute to initial recognition of bacterial glycans, thus providing an early defence mechanism against bacterial infections, but they may also be exploited by bacteria to escape immune responses. In this review, we will first exemplify bacterial glycosylation systems; we will then describe modes of recognition of bacterial glycans by lectins in innate immunity and, finally, we will briefly highlight how bacteria have found ways to exploit these interactions to evade immune recognition.

The extensive post-translational modifications of the envelope spikes of the human immunodeficiency virus (HIV) present considerable challenges and opportunities for HIV vaccine design. These oligomeric glycoproteins typically have over 30 disulfide bonds and around a 100 N-linked glycosylation sites, and are functionally dependent on protease cleavage within the secretory system. The resulting mature structure adopts a compact fold with the vast majority of its surface obscured by a protective shield of glycans which can be targeted by broadly neutralizing antibodies (bnAbs). Despite the notorious heterogeneity of glycosylation, rare B-cell lineages can evolve to utilize and cope with viral glycan diversity, and these structures therefore present promising targets for vaccine design. The latest generation of recombinant envelope spike mimetics contains re-engineered post-translational modifications to present stable antigens to guide the development of bnAbs by vaccination.

Glycosylation is a major form of enzymatic modification of organic molecules responsible for multiple biological processes in an organism. The biosynthesis of glycans is controlled by a series of glycosyltransferases, glycosidases and glycan-modifying enzymes that collectively assemble and process monosaccharide moieties into a diverse array of structures. Many studies have provided insight into various pathways of glycosylation at the ocular surface, such as those related to the biosynthesis of mucin-type O -glycans and N -glycans on proteins, but many others still remain largely unknown. This review provides an overview of the different classes of glycans described at the ocular surface focusing on their biosynthetic pathways and biological relevance. A precise understanding of these pathways under physiological and pathological conditions could help identify biomarkers and novel targets for therapeutic intervention.

The gastrointestinal mucosal surface is the primary interface between internal host tissues and the vast microbiota. Mucins, key components of mucus, are high-molecular-weight glycoproteins characterized by the presence of many O -linked oligosaccharides to the core polypeptide. They play many biological functions, helping to maintain cellular homeostasis and to establish symbiotic relationships with complex microbiota. Mucin O -glycans exhibit a huge variety of peripheral sequences implicated in the binding of bacteria to the mucosal tissues, thereby playing a key role in the selection of specific species and in the tissue tropism displayed by commensal and pathogenic bacteria. Bacteria have evolved numerous strategies to colonize host mucosae, and among these are modulation of expression of cell surface adhesins which allow bacteria to bind to mucins. However, despite well structurally characterized adhesins and lectins, information on the nature and structure of oligosaccharides recognized by bacteria is still disparate. This review summarizes the current knowledge on the structure of epithelial mucin O -glycans and the interaction between host and commensal or pathogenic bacteria mediated by mucins.

During the last 10 years it has become apparent that a significant subset of inherited muscular dystrophy is caused by errors in the glycosylation of α-dystroglycan. Many of these dystrophies are also associated with abnormalities of the central nervous system. Dystroglycan has to be fully glycosylated in order bind to its ligands. To date, six genes have been shown to be essential for functional dystroglycan glycosylation and most, if not all, of these genes act in the formation of O-mannosyl glycans. Genetic heterogeneity indicates that other genes are involved in this pathway. Identification of these additional genes would increase our understanding of this specific and essential glycosylation pathway.

Melanoma, which is one of the most aggressive human tumours, originates from melanin-producing melanocytes. As no effective systemic therapy exists for advanced-stage melanoma, the best chance of recovery remains surgical removal of thin early-stage melanoma. Aberrant glycosylation is a hallmark of malignancy and a well-studied class of β1,6-branched oligosaccharides is associated with malignant transformation of rodent and human cells, and poor prognosis in cancer patients. It is evident that increased β1,6 branching significantly contributes to the phenotype of melanoma cells, influencing the adhesion to extracellular matrix components and motility as well as invasive and metastatic potential. Despite the considerable success in establishing the role of β1,6-branched N-linked oligosaccharides in melanoma biology, there is virtually no progress in using these glycans as a screening tool for the early diagnosis of the disease, or a target-specific therapeutic agent.

A common phenotypic change in cancer is a dramatic transformation of cellular glycosylation. Functional studies of particular tumour-associated oligosaccharides are difficult to interpret conclusively, but carbohydrate-binding proteins are likely to contribute to progression of the tumour. This review discusses the potential role of CLRs (C-type lectin receptors), expressed by antigen-presenting cells of the immune system, in tumour recognition and immune modulation. Studies in recent years have provided significant insight into the immunomodulatory function of CLR during infections, but their role in cancer remains elusive; some strongly bind tumour cells and antigens, indicating participation in malignancy. The potential to use recombinant CLR as diagnostic tools will also be discussed.

Glycans stand out from all classes of biomolecules because of their unsurpassed structural complexity. This is generated by variability in anomeric status of the glycosidic bond and its linkage points, ring size, potential for branching and introduction of diverse site-specific substitutions. What poses an enormous challenge for analytical processing is, at the same time, the basis for the fingerprint-like glycomic profiles of glycoconjugates and cells. What's more, the glycosylation machinery is sensitive to disease manifestations, earning glycan assembly a reputation as a promising candidate to identify new biomarkers. Backing this claim for a perspective in clinical practice are recent discoveries that even seemingly subtle changes in the glycan structure of glycoproteins, such as a N-glycan core substitution by a single sugar moiety, have far-reaching functional consequences. They are brought about by altering the interplay between the glycan and (i) its carrier protein and (ii) specific receptors (lectins). Glycan attachment thus endows the protein with a molecular switch and new recognition sites. Co-ordinated regulation of glycan display and presentation of the cognate lectin, e.g. in cancer growth regulation exerted by a tumour suppressor, further exemplifies the broad functional dimension inherent to the non-random shifts in glycosylation. Thus studies on glycobiomarkers converge with research on how distinct carbohydrate determinants are turned into bioactive signals.

Glycosylation modifications have been reported in a number of disease states and, as a result, there is significant focus on the discovery and development of glycan-based biomarkers. Glyco-biomarkers have the potential to enhance the efficacy and efficiency of the diagnostic procedures for these diseases.

The development of glycoanalytical HPLC-based high-throughput technology has greatly enhanced the study of glycobiology, facilitating the discovery of disease-related solutions and providing an informative view of glycosylation and its relationship with other biological disciplines in a systems biology approach.

With glycosylation now firmly established across both Archaeal and bacterial proteins, a wide array of glycan diversity has become evident from structural analysis and genomic data. These discoveries have been built in part on the development and application of mass spectrometric technologies to the bacterial glycoproteome. This review highlights recent findings using high sensitivity MS of the large variation of glycans that have been reported on flagellin and pilin proteins of bacteria, using both ‘top down’ and ‘bottom up’ approaches to the characterization of these glycoproteins. We summarize current knowledge of the sugar modifications that have been observed on flagellins and pilins, in terms of both the diverse repertoire of monosaccharides observed, and the assemblage of moieties that decorate many of these sugars.

The glycan part of cellular glycoconjugates affords a versatile means to build biochemical signals. These oligosaccharides have an exceptional talent in this respect. They surpass any other class of biomolecule in coding capacity within an oligomer (code word). Four structural factors account for this property: the potential for variability of linkage points, anomeric position and ring size as well as the aptitude for branching (first and second dimensions of the sugar code). Specific intermolecular recognition is favoured by abundant potential for hydrogen/co-ordination bonds and for C–H/π-interactions. Fittingly, an array of protein folds has developed in evolution with the ability to select certain glycans from the natural diversity. The thermodynamics of this reaction profits from the occurrence of these ligands in only a few energetically favoured conformers, comparing favourably with highly flexible peptides (third dimension of the sugar code). Sequence, shape and local aspects of glycan presentation (e.g. multivalency) are key factors to regulate the avidity of lectin binding. At the level of cells, distinct glycan determinants, a result of enzymatic synthesis and dynamic remodelling, are being defined as biomarkers. Their presence gains a functional perspective by co-regulation of the cognate lectin as effector, for example in growth regulation. The way to tie sugar signal and lectin together is illustrated herein for two tumour model systems. In this sense, orchestration of glycan and lectin expression is an efficient means, with far-reaching relevance, to exploit the coding potential of oligosaccharides physiologically and medically.

The TSEs (transmissible spongiform encephalopathies) are not only devastating neurological diseases but also provide a biochemical conundrum; how can a disease agent replicate in the apparent absence of genetic material? The prion hypothesis proposes that the TSE agent is a misfolded form of the host glycoprotein PrP (prion protein). However, a number of questions regarding the hypothesis remain to be addressed. We are using gene-targeted PrP transgenics models to investigate these issues. Here we discuss our recent results that examine the importance of PrP's N-glycans to the misfolding of the protein.

β-Amyloid, a neurotoxic peptide deposited in the brains of Alzheimer's disease patients, is released by a series of membrane-limited proteolytic events. β-Secretase activity is enhanced by cellular targeting into intracellular cholesterol-rich microdomains, which are dispersed by statins.