Sialic acid utilization by bacterial pathogens

Severi, Emmanuele; Hood, Derek W.; Thomas, Gavin H.

doi:10.1099/mic.0.2007/009480-0

Cited by 417 publications

(463 citation statements)

References 40 publications

(59 reference statements)

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“…Sialic acid is often found on pathogenic bacteria, such as C. jejuni, Haemophilus influenzae, Neisseria gonorrheae, Neisseria meningitidis, and Pasteurella multocida (27). The incorporation of host-derived α2,3-linked sialic acid into H. influenzae is a major virulence factor for experimental otitis (28).…”

Section: Discussionmentioning

confidence: 99%

Milk oligosaccharide sialyl(α2,3)lactose activates intestinal CD11c ⁺ cells through TLR4

Kurakevich

Hennet

Hausmann

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Breast milk oligosaccharides shape the intestinal environment by affecting mucosal immunity and bacterial colonization. To clarify the role of milk oligosaccharide sialyl(α2,3)lactose (3SL) in intestinal physiology and disease, we investigated colitis development in Il10 −/− mice exposed to normal or 3SL-deficient milk during lactation. Onset and progression of intestinal inflammation were delayed in Il10 −/− mice deficient for the α2,3 sialyltransferase 4 (ST3GAL4) responsible for 3SL biosynthesis. The proinflammatory role of 3SL was confirmed by showing that oral supplementation of newborn Il10 −/− ;St3gal4 −/− mice with 3SL increased colitis severity. Conversely, fostering of newborn Il10 −/− mice to lactating St3gal4 −/− mothers reduced colitis severity. 3SL directly stimulated mesenteric lymph node CD11c + dendritic cells and induced production of cytokines required for expansion of T H 1 and T H 17 T cells. The stimulatory effect of 3SL was attenuated in Tlr4-deficient CD11c + cells, demonstrating that 3SL induces inflammation through Toll-like receptor 4 (TLR4) signaling. Thus, 3SL directly modulates mucosal immunity, which increases susceptibility to colitis.carbohydrate | glycan | prebiotics | mouse innate immunity I nflammatory bowel disease (IBD) affects up to 0.8% of the Western population and this number is constantly growing worldwide (1). The etiology of IBD is not fully understood, although a number of genetic and environmental factors leading to aberrant mucosal immune responses have been identified (2). Nutrition and especially breastfeeding affects the risk for IBD (3). Breastfeeding for at least 3 mo, accordingly, contributes to a lower incidence for IBD (4); however, these data still are controversial. Oligosaccharides are major constituents of breast milk fulfilling various functions, such as promoting growth of beneficial bacteria, acting as soluble receptors preventing attachment of pathogens in the gastrointestinal tract, and reducing adhesion of leukocytes (4, 5). The exact functions of individual oligosaccharides remain however largely unknown.The limited structural diversity of mouse milk oligosaccharides, including only sialyl(α2,3)lactose (3SL) and sialyl(α2,6)lactose (6SL), enables assessing the specific functional contribution of these oligosaccharides to intestinal homeostasis (6). A recent study provided unique evidence that milk-derived 3SL, but not 6SL, increased susceptibility to dextran sulfate sodium (DSS)-induced acute colitis (6). These findings indicate that individual milk oligosaccharides may not only mediate protective effects, but may promote inflammation as well.Mucosal innate immunity has a pivotal role in regulating inflammatory responses (2). Dendritic cells (DCs) and macrophages sense luminal antigens and provide signals for induction of tolerance to ingested antigens and commensal bacteria or for initiation of inflammatory immune responses, facilitating activation of adaptive immunity (7,8). Intestinal DCs consist of two functionally distinct subsets based on e...

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Section: Discussionmentioning

confidence: 99%

Milk oligosaccharide sialyl(α2,3)lactose activates intestinal CD11c ⁺ cells through TLR4

Kurakevich

Hennet

Hausmann

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…Supporting the putative function of GT97 family members as NulO transferases, the genome sequences of all of the identified organisms were found to harbor homologs of other nonulosonic acid biosynthesis genes, specifically NulO synthases (32,30) and CMPNulO synthetase (33,30). Although the role of sialylated structures in commensal organisms and opportunistic pathogens is generally understood to be the avoidance of the immune system by molecular mimicry of host structures (34), the functional significance of GT97 family proteins in extreme halophiles is less clear. The phylogenetic tree for the new family revealed clustering that is largely at odds with the true phylogenetic relationships among these organisms (Fig.…”

Section: Volume 289 • Number 49 • December 5 2014mentioning

confidence: 99%

Dissection of Hexosyl- and Sialyltransferase Domains in the Bifunctional Capsule Polymerases from Neisseria meningitidis W and Y Defines a New Sialyltransferase Family

Romanow

Keys

Stummeyer

et al. 2014

Journal of Biological Chemistry

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Background: Capsule polymerases of Neisseria meningitidis serogroups W and Y comprise hexosyl-and sialyltransferase activity. Results: Hexosyltransferase activity is encoded by the predicted N-terminal GT-B fold. Sialyltransferase activity requires 168 additional amino acids upstream of the predicted C-terminal GT-B fold. Conclusion:The sialyltransferase domains of NmW/Y define a new glycosyltransferase (CAZy) family. Significance: The new CAZy family comprises sequences from distantly related species.

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“…They protect against hydrolysis of the glycosidic or peptide bonds of oligosaccharides, glycoproteins, glycolipids and gangliosides located on eukaryotic cell surfaces, and against degradation of the ECM. In addition, sialylated lipopolysaccharide and polysialic acid capsules are surface features of certain Gram-negative and Gram-positive bacteria [19].…”

Section: Introductionmentioning

confidence: 99%

Genetic variation in sialidase and linkage to N-acetylneuraminate catabolism in Mycoplasma synoviae

May

Brown

2008

Microbial Pathogenesis

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We explored the genetic basis for intraspecific variation in mycoplasmal sialidase activity that correlates with virulence, and its potentially advantageous linkage to nutrient catabolism. Polymorphism in N-acetylneuraminate scavenging and degradation genes (sialidase, Nacetylneuraminate lyase, N-acetylmannosamine kinase, N-acetylmannosamine-6-phosphate epimerase, N-acetylglucosamine-6-phosphate deacetylase, and glucosamine-6-phosphate deaminase) was evident among eight strains of the avian pathogen Mycoplasma synoviae. Most differences were single nucleotide polymorphisms, ranging from 0.34 ± 0.04 substitutions per 100 bp for N-acetylmannosamine kinase to 0.65 ± 0.03 for the single-copy sialidase gene nanI. Missense mutations were twice as common as silent mutations in nanI; 26% resulted in amino acids dissimilar to consensus; and there was a 12-base deletion near the nanI promoter in strain WVU1853 T , supporting a complex genetic basis for differences in sialidase activity. Two strains had identical frameshifts in the N-acetylneuraminate lyase gene nanA, resulting in nonsense mutations, and both had downstream deletions in nanA. Such genetic lesions uncouple extracellular liberation of sialic acid from generation of fructose-6-phosphate and pyruvate via intracellular N-acetylneuraminate degradation. Retention of nanI by such strains, but not others in the M. synoviae phylogenetic cluster, is evidence that sialidase has an important non-nutritional role in the ecology of M. synoviae and certain other mycoplasmas.

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Sialic acid utilization by bacterial pathogens

Cited by 417 publications

References 40 publications

Milk oligosaccharide sialyl(α2,3)lactose activates intestinal CD11c ⁺ cells through TLR4

Milk oligosaccharide sialyl(α2,3)lactose activates intestinal CD11c ⁺ cells through TLR4

Dissection of Hexosyl- and Sialyltransferase Domains in the Bifunctional Capsule Polymerases from Neisseria meningitidis W and Y Defines a New Sialyltransferase Family

Genetic variation in sialidase and linkage to N-acetylneuraminate catabolism in Mycoplasma synoviae

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Sialic acid utilization by bacterial pathogens

Cited by 417 publications

References 40 publications

Milk oligosaccharide sialyl(α2,3)lactose activates intestinal CD11c + cells through TLR4

Milk oligosaccharide sialyl(α2,3)lactose activates intestinal CD11c + cells through TLR4

Dissection of Hexosyl- and Sialyltransferase Domains in the Bifunctional Capsule Polymerases from Neisseria meningitidis W and Y Defines a New Sialyltransferase Family

Genetic variation in sialidase and linkage to N-acetylneuraminate catabolism in Mycoplasma synoviae

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Milk oligosaccharide sialyl(α2,3)lactose activates intestinal CD11c ⁺ cells through TLR4

Milk oligosaccharide sialyl(α2,3)lactose activates intestinal CD11c ⁺ cells through TLR4