Exploration of Sialic Acid Diversity and Biology Using Sialoglycan Microarrays

Deng, Lih‐Wen; Chen, Xi; Varki, Ajit

doi:10.1002/bip.22314

Cited by 49 publications

(35 citation statements)

References 229 publications

(336 reference statements)

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“…To further explore Rg NanH ligand specificity, Rg CBM40 and inactive mutant Rg GH33 D282A, were tested for binding to various sialoglycans, using a slide microarray 38 , 39 . This sialoglycan microarray presents over 60 synthetically recreated naturally occurring oligosaccharide structures with diverse sialic acid forms, glycosidic linkages, and underlying glycans, representing a broad range of such targets 38 , 39 . Both recombinant proteins exclusively bound to glycans terminated with sialic acids (Fig.…”

Section: Resultsmentioning

confidence: 99%

Unravelling the specificity and mechanism of sialic acid recognition by the gut symbiont Ruminococcus gnavus

et al. 2017

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Ruminococcus gnavus is a human gut symbiont wherein the ability to degrade mucins is mediated by an intramolecular trans-sialidase (RgNanH). RgNanH comprises a GH33 catalytic domain and a sialic acid-binding carbohydrate-binding module (CBM40). Here we used glycan arrays, STD NMR, X-ray crystallography, mutagenesis and binding assays to determine the structure and function of RgNanH_CBM40 (RgCBM40). RgCBM40 displays the canonical CBM40 β-sandwich fold and broad specificity towards sialoglycans with millimolar binding affinity towards α2,3- or α2,6-sialyllactose. RgCBM40 binds to mucus produced by goblet cells and to purified mucins, providing direct evidence for a CBM40 as a novel bacterial mucus adhesin. Bioinformatics data show that RgCBM40 canonical type domains are widespread among Firmicutes. Furthermore, binding of R. gnavus ATCC 29149 to intestinal mucus is sialic acid mediated. Together, this study reveals novel features of CBMs which may contribute to the biogeography of symbiotic bacteria in the gut.

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Section: Resultsmentioning

confidence: 99%

Unravelling the specificity and mechanism of sialic acid recognition by the gut symbiont Ruminococcus gnavus

et al. 2017

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“…Glutathione S -transferase (GST)-tagged BRs of GspB, Hsa, and SrpA (see Table S1 for details), were tested for binding to various sialoglycans, using a recently developed slide microarray. This unique sialoglycan microarray presents over 70 synthetically recreated naturally-occurring oligosaccharide structures with diverse sialic acid forms, glycosidic linkages, and underlying glycans, representing the broadest range of such targets available to date [23] , [29] . All three proteins exclusively bound to glycans terminated with sialic acids but not non-sialylated ones ( Figure 1A–1D ).…”

Section: Resultsmentioning

confidence: 99%

“…Glycan-mediated host-pathogen interactions are involved in various human disease processes [21] . Sialic acids (Sias) are a diverse group of α-keto acids with a shared nine-carbon backbone [22] , [23] . Given their presence at terminal positions of cell surface and secreted glycoconjugates, they mediate or modulate various biological interactions [24] , [25] .…”

Section: Introductionmentioning

confidence: 99%

Oral Streptococci Utilize a Siglec-Like Domain of Serine-Rich Repeat Adhesins to Preferentially Target Platelet Sialoglycans in Human Blood

et al. 2014

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Damaged cardiac valves attract blood-borne bacteria, and infective endocarditis is often caused by viridans group streptococci. While such bacteria use multiple adhesins to maintain their normal oral commensal state, recognition of platelet sialoglycans provides an intermediary for binding to damaged valvular endocardium. We use a customized sialoglycan microarray to explore the varied binding properties of phylogenetically related serine-rich repeat adhesins, the GspB, Hsa, and SrpA homologs from Streptococcus gordonii and Streptococcus sanguinis species, which belong to a highly conserved family of glycoproteins that contribute to virulence for a broad range of Gram-positive pathogens. Binding profiles of recombinant soluble homologs containing novel sialic acid-recognizing Siglec-like domains correlate well with binding of corresponding whole bacteria to arrays. These bacteria show multiple modes of glycan, protein, or divalent cation-dependent binding to synthetic glycoconjugates and isolated glycoproteins in vitro. However, endogenous asialoglycan-recognizing clearance receptors are known to ensure that only fully sialylated glycans dominate in the endovascular system, wherein we find these particular streptococci become primarily dependent on their Siglec-like adhesins for glycan-mediated recognition events. Remarkably, despite an excess of alternate sialoglycan ligands in cellular and soluble blood components, these adhesins selectively target intact bacteria to sialylated ligands on platelets, within human whole blood. These preferred interactions are inhibited by corresponding recombinant soluble adhesins, which also preferentially recognize platelets. Our data indicate that circulating platelets may act as inadvertent Trojan horse carriers of oral streptococci to the site of damaged endocardium, and provide an explanation why it is that among innumerable microbes that gain occasional access to the bloodstream, certain viridans group streptococci have a selective advantage in colonizing damaged cardiac valves and cause infective endocarditis.

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“…33,34 Indeed, by isolating cellular glycans from desired cells and enriching for sialylated species, it is feasible to design microarrays consisting of cell-specific sialylated glycans, which would be useful in studying how pathogenic neuraminidases interact with specific cells during infection. The method reported here has the potential to provide insight into neuraminidase specificities and how underlying glycans can contribute to that specificity, thereby increasing our understanding of how neuraminidase activity contributes to infection.…”

Section: Discussionmentioning

confidence: 99%

Glycan specificity of neuraminidases determined in microarray format

McCombs

Diaz

Luebke

et al. 2016

Carbohydrate Research

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Neuraminidases hydrolytically remove sialic acids from glycoconjugates. Neuraminidases are produced by both humans and their pathogens, and function in normal physiology and in pathological events. Identification of neuraminidase substrates is needed to reveal their mechanism of action, but high-throughput methods to determine glycan specificity of neuraminidases do not exist. Here we use two glycan labeling reactions to monitor neuraminidase activity toward glycan substrates. While both periodate oxidation and aniline-catalyzed oxime ligation (PAL) and galactose oxidase and aniline-catalyzed oxime ligation (GAL) can be used to monitor neuraminidase activity toward glycans in microtiter plates, only GAL accurately measured neuraminidase activity toward glycans displayed on a commercial glass slide microarray. Using GAL, we confirm known linkage specificities of three pneumococcal neuraminidases and obtain new information about underlying glycan specificity.

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Exploration of Sialic Acid Diversity and Biology Using Sialoglycan Microarrays

Cited by 49 publications

References 229 publications

Unravelling the specificity and mechanism of sialic acid recognition by the gut symbiont Ruminococcus gnavus

Unravelling the specificity and mechanism of sialic acid recognition by the gut symbiont Ruminococcus gnavus

Oral Streptococci Utilize a Siglec-Like Domain of Serine-Rich Repeat Adhesins to Preferentially Target Platelet Sialoglycans in Human Blood

Glycan specificity of neuraminidases determined in microarray format

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