Glycan recognition at the saliva – oral microbiome interface

Cross, Benjamin; Rühl, Stefan

doi:10.1016/j.cellimm.2018.08.008

Cited by 82 publications

(70 citation statements)

References 300 publications

(328 reference statements)

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“…4A,B). While the proteins in saliva differ from those found in 215 respiratory mucus, they do contain some of the same heavily glycosylated proteins including mucins like MUC5B (49)(50)(51). Human saliva was similar to the secreted mucus from NHBE and A549 cells in containing primarily Neu5Ac with little 9-O-Ac Sia, and the composition of dog saliva showed a similar profile.…”

Section: Analysis Of Modified Sia In Saliva Mucus and On Erythrocytmentioning

confidence: 85%

“…To define the variation of modified Sia present in secreted mucus across different animals, we examined saliva as it contains many of the same 355 heavily glycosylated proteins and mucins, including MUC5B, that are present in respiratory mucus (49)(50)(51). We found a great deal of variability in both the amounts and types of modified has been proposed to be a potent inhibitor of many types of viral and bacterial neuraminidases, and to be the γ-inhibitor of horse serum, where it may be present at high levels on the α-2 macroglobulin protein (56,65,68).…”

Section: Variation In Saliva and Other Mucinsmentioning

confidence: 99%

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The effects of modified sialic acids on mucus and erythrocytes on influenza A virus HA and NA functions

Barnard

Alford-Lawrence

Buchholz

et al. 2019

Preprint

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25Sialic acids (Sia) are the primary receptors for influenza viruses, and are widely displayed on cell surfaces and in secreted mucus. Sia may be present in variant forms that include O-acetyl modifications at C4, C7, C8, and C9 positions, and N-acetyl or N-glycolyl at C5. They can also vary in their linkages, including α2-3 or α2-6-linkages. Here, we analyzed the distribution of modified Sia in cells and tissues of wild-type mice, or in mice lacking cytidine 5'-30 monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) enzyme that synthesizes Nglycolyl modifications (Neu5Gc). We also examined the variation of Sia forms on erythrocytes and saliva from different animals. To determine the effect of Sia modifications on influenza A virus (IAV) infection, we tested for effects on hemagglutinin (HA) binding and neuraminidase (NA) cleavage. We confirmed that 9-O-acetyl, 7,9-O-acetyl, 4-O-acetyl, and Neu5Gc 35 modifications are widely but variably expressed in mouse tissues, with the highest levels detected in the respiratory and gastrointestinal tracts. Secreted mucins in saliva and surface proteins of erythrocytes showed a great degree of variability in display of modified Sia between different species. IAV HA from different virus strains showed consistently reduced binding to both Neu5Gc and O-acetyl modified Sia; however, while IAV NA were inhibited by Neu5Gc and 40 O-acetyl modifications, there was significant variability between NA types. The modifications of Sia in mucus may therefore have potent effects on the functions of IAV, and may affect both pathogens and the normal flora of different mucosal sites. (241 words) IMPORTANCE 45Sialic acids (Sia) are involved in many different cellular functions and are receptors for many pathogens. Sia come in many chemically modified forms but we lack a clear understanding of how they alter the interactions with microbes. Here we examine the expression of modified Sia in mouse tissues, on secreted mucus in saliva, and on erythrocytes, including those from IAV host species and animals used in IAV research. These Sia forms varied considerably between

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Section: Analysis Of Modified Sia In Saliva Mucus and On Erythrocytmentioning

confidence: 85%

Section: Variation In Saliva and Other Mucinsmentioning

confidence: 99%

The effects of modified sialic acids on mucus and erythrocytes on influenza A virus HA and NA functions

Barnard

Alford-Lawrence

Buchholz

et al. 2019

Preprint

Self Cite

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“…The mucins protein evolution is driven by a "Red Queen" effect, in which hosts are constantly in a race to evade the more rapidly evolving pathogens that infect them 35,36 .…”

Section: Lately Developedmentioning

confidence: 99%

Conservation motifs - a novel evolutionary-based classification of proteins

Beer

Sherill-Rofe

Unterman

et al. 2020

Preprint

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Cross-species protein conservation patterns, as directed by natural selection, are indicative of the interplay between protein function, protein-protein interaction and evolution. Since the beginning of the genomic era, proteins were characterized as either conserved or not conserved. This simple classification became archaic and cursory once data on protein orthologs became available for thousands of species.To enrich the language used to describe protein conservation patterns, and to understand their biological significance, we classified 20,294 human proteins against 1096 species. Analyses of the conservation patterns of human proteins in different eukaryotic clades yielded extremely variable and rich patterns that had never been characterized or studied before. Using mathematical classifications, we defined seven conservation motifs: Steps, Critical, Lately Developed, Plateau, Clade Loss, Trait Loss and Gain, which describe the evolution of human proteins.One type of motif, which we termed Gain, describes the human proteins that are highly conserved in a small number of organisms but are not found in most other species.Interestingly, this pattern predicts 73 possible instances of horizontal gene transfer in eukaryotes.Overall, our work offers novel terms for conservation patterns and defines a new language intended to classify proteins based on evolution, reveal aspects of protein evolution, and improve the understanding of protein functions.

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“…These functions include the breakdown of dietary starch by the salivary enzyme amylase (Ragunath et al, 2008) , the provision of calcium phosphate to maintain mineralization of tooth enamel (Moreno et al, 1979) , and host defense against pathogenic microorganisms while maintaining a beneficial commensal microbiome in the mouth (Cross and Ruhl, 2018;Heo et al, 2013) . Saliva also possesses physicochemical properties keeping the oral cavity moist and well lubricated, which are equally provided by saliva proteins, especially mucins (Frenkel and Ribbeck, 2015;Tabak et al, 1982) .…”

Section: Introductionmentioning

confidence: 99%

Functional specialization of human salivary glands and origins of proteins intrinsic to human saliva

Saitou

Gaylord²,

et al. 2020

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Salivary proteins facilitate food perception and digestion, maintain the integrity of the mineralized tooth and oral epithelial surfaces, and shield the oro-digestive tract from environmental hazards and invading pathogens. Saliva, as one of the easiest to collect body fluids, also serves in diagnostic applications, with its proteins providing a window to body health. However, despite the availability of the human saliva proteome, the origins of individual proteins remain unclear. To bridge this gap, we analyzed the transcriptomes of 27 tissue samples derived from the three major types of human adult and fetal salivary glands and integrated these data with the saliva proteome and the proteomes and transcriptomes of 28+ other human organs, with tissue expression confirmed by 3D microscopy. Using these tools, we have linked saliva proteins to their source for the first time, an outcome with significant implications for basic research and diagnostic applications. Furthermore, our study represents the first comparative transcriptomic analysis of human adult and fetal exocrine organs, providing evidence that functional specialization occurs late in salivary gland development, and is driven mainly by the transcription of genes encoding secreted saliva proteins. Moreover, we found that dosage of abundant saliva proteins secreted by the salivary glands is primarily regulated at the transcriptional level, and that secreted proteins can be synthesized by distinct subsets of serous acinar cells, revealing hitherto unrecognized heterogeneity in the acinar cell lineage. Our results reveal the functional underpinnings of these secretory organs, paving the way for future investigations into saliva biology and pathology. SIGNIFICANCE STATEMENTSaliva facilitates the perception and digestion of food while regulating the homeostasis of microbes in the mouth and their transduction to the digestive tract. Proteins in saliva fluid are responsible for these diverse and important functions. 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.

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Glycan recognition at the saliva – oral microbiome interface

Cited by 82 publications

References 300 publications

The effects of modified sialic acids on mucus and erythrocytes on influenza A virus HA and NA functions

The effects of modified sialic acids on mucus and erythrocytes on influenza A virus HA and NA functions

Conservation motifs - a novel evolutionary-based classification of proteins

Functional specialization of human salivary glands and origins of proteins intrinsic to human saliva

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