A perspective based on a 2020 NIH workshop, outlining where glycoscience intersects with infection and immunity and how new glycan tools and resources can advance research.

Using silica surfaces with seven different chemical coatings, the study shows that the amount of saliva and serum protein that adsorbs depends on the coating, but not in a way that simple surface properties such as wettability, surface energy, or charge can predict.

Introduces the Human Salivary Proteome Wiki, a public, community-curated database that collects and annotates information on the proteins found in human saliva.

To understand the glandular origins of proteins in saliva, we performed the hitherto most comprehensive investigation of gene expression in healthy human salivary glands. Our results revealed that each mature salivary gland type contributes a distinct repertoire of proteins to saliva. We provide evidence that these unique, gland-specific secreted protein profiles emerge late in gland development. Our results suggest that the origins of salivary proteins in whole mixed saliva can be parsed out only through an integrative analysis of both protein and RNA levels.

Chemically modified forms of sialic acid found on mucus, in saliva, and on red blood cells of different animals can inhibit binding and cleavage by influenza A virus hemagglutinin and neuraminidase.

Here, we compared the proteomes of human saliva and the saliva of our closest extant evolutionary relatives, chimpanzees and gorillas, using macaques as an outgroup, with the aim to uncover features in saliva protein composition that are unique to each species. We found that humans produce a waterier saliva, containing less than half total protein than great apes and Old World monkeys. For all major salivary proteins in humans, we could identify counterparts in chimpanzee and gorilla saliva. However, we discovered unique protein profiles in saliva of humans that were distinct from those of nonhuman primates. These findings open up the possibility that dietary differences and pathogenic pressures may have shaped a distinct salivary proteome in the human lineage.

Here, we present comprehensive evidence for AMY copy number expansions that independently occurred in several mammalian species which consume diets rich in starch. We also provide correlative evidence that AMY gene duplications may be an essential first step for amylase to be expressed in saliva. Our findings underscore the overall importance of gene copy number amplification as a flexible and fast evolutionary mechanism that can independently occur in different branches of the phylogeny.

Review article describing the important roles of salivary glycans in oral microbial ecology and host defense.

Our investigation revealed a significant association of MUC7 haplotypic variation with the composition of the oral microbiome. Furthermore, we conclude that a divergent MUC7 haplotype likely originated in an unknown African hominin population and introgressed into ancestors of modern Africans.

Traces how the gene for the salivary mucin MUC7 has changed in recent human and primate evolution, with a focus on variation in its glycosylated repeat region.

Shows that Streptococcus pneumoniae lacking its polysaccharide capsule binds the salivary mucin MUC7 through recognition of its glycans, a binding that the capsule normally masks.

Oral streptococci use the Siglec-like binding domain of their serine-rich repeat adhesins to selectively target sialic acid-containing glycans on platelets in human blood, with implications for infective endocarditis.

Describes an overlay method for screening the many species of dental plaque and other mixed biofilms for bacteria that adhere to one another (coadhesion partners).

Review of how saliva and its components interact with oral microbes, and how salivary gland dysfunction can disturb this balance.

Review of how salivary proteins bind to commensal and pathogenic bacteria, and what these interactions mean for oral and systemic health.

Examines which salivary proteins adsorb to different dental material surfaces and how this protein layer influences the adhesion of Streptococcus gordonii.

Identifies human salivary proteins with host-defense functions that bind to Staphylococcus aureus.

Review arguing that, with the salivary proteome now catalogued, research should return to the basic functions of saliva and its proteins.

Characterizes surfaces coated with PAMAM dendrimers carrying positively or negatively charged end groups, including how the coatings change under liquid interface stress.

Tests how grafting dendrimers onto model silicon surfaces affects protein adsorption and the subsequent adhesion of bacteria.

Assesses whether gamma irradiation can sterilize human saliva samples while keeping their proteins intact for research use.

Profiles the expression of outer membrane proteins, including adhesins, across clinical isolates of Helicobacter pylori.

Uses silicon wafers as a model to test how an adsorbed protein film alters the performance of antibacterial and bacteria-repellent surface coatings.

Compares salivary protein profiles of young children with and without early childhood caries.

Uses a fluorescence-based two-dimensional bacterial overlay to identify salivary glycoproteins that serve as receptors for the Helicobacter pylori adhesins BabA and SabA.

Investigates whether Helicobacter pylori found in the mouth relates to H. pylori infection of the stomach in the same patients.

Compares how human cells and Staphylococcus aureus adhere to silicon model surfaces with different chemical modifications.

Introduces a fluorescence-based overlay method for measuring bacteria attached to surfaces directly in place, for many samples at once.

Presents a chemiluminescence-based method to measure and compare the amounts of protein adsorbed on chemically modified silica surfaces.

Methods chapter on studying how Helicobacter pylori binds to host carbohydrates through its adhesins.

Compares the protein make-up of parotid and submandibular-sublingual gland secretions with whole saliva using two-dimensional gel electrophoresis.

Uses glycoconjugate arrays to identify and characterize the carbohydrate structures that Helicobacter pylori binds.

Follows how the protein composition of whole saliva changes during the first year of life.

Identifies the salivary molecules recognized by the proline-rich protein-binding and lectin-like adhesins of oral actinomyces and streptococci.

Examines salivary proteins and cytokines in patients with gingival overgrowth caused by medication.

Characterizes the binding of viridans group streptococci to receptors containing sialic acid, galactose, or N-acetylgalactosamine.

Identifies the receptors on neutrophils and HL-60 cells that are recognized by adhesins of Streptococcus gordonii and Actinomyces naeslundii.

Discusses specific inhibitors of bacterial adhesion, based on studies of the gram-positive bacteria that first colonize the tooth surface.

Links a specific cell surface antigen of Streptococcus gordonii to its ability to agglutinate red blood cells and bind α2-3-linked sialic acid receptors.

Shows that lectins of oral actinomyces and streptococci recognize the glycans of human IgA1.

Identifies candidate glycoprotein and glycolipid receptors on neutrophils for the lectin of Actinomyces naeslundii WVU45.

Shows that interferon-γ blocks the interleukin-6-induced expression of interleukin-4 receptors in mouse myeloid cells at the level of transcription.

Shows that mouse myeloid progenitor cells produce a soluble form of the interleukin-4 receptor when stimulated with interleukin-6 and interferon-γ.

Shows that interferon-γ and interleukin-6 can separate early and late markers of myeloid differentiation in mouse cells.

Shows that interleukin-1 increases interleukin-2 receptor expression on differentiating myeloid cells.

Shows that the brief appearance of the IL-2 receptor α-chain on IL-6-stimulated myeloid cells is controlled by prostaglandin E2 that the cells produce themselves.

Shows that interleukin-6 regulates interleukin-4 receptor expression on mouse myeloid progenitor cells.

Shows that interleukin-6 induces interferon-β and 2'5'-oligoadenylate synthetase mRNA as mouse myeloid cells differentiate.

Shows that adenosine and related compounds steer human monocytes toward becoming highly accessory cells rather than macrophages.

Describes the generation of veiled accessory cells from human blood monocytes.