Two Trans-sialidase Forms with Different Sialic Acid Transfer and Sialidase Activities from Trypanosoma congolense

Tiralongo, Evelin; Schrader, Silke; Lange, Hans; Lemke, Hilmar; Tiralongo, Joe; Schauer, Roland

doi:10.1074/jbc.m212909200

Cited by 33 publications

(53 citation statements)

References 54 publications

(46 reference statements)

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“…Despite this inhibition, TbTS RNAi knockdown parasites maintain a high level of sialidase activity, which is efficiently diminished by interference of the TbSA C gene, indicating the present of a novel sialidase on the surface membrane of procyclic T. brucei. Recently, the purification and characterization of two transsialidase forms from another African trypanosome species, T. congolense (27), has been reported and the partial sequences of their genes determined (21). The deduced amino acid sequences reported here are ϳ40% identical to T. brucei transsialidase and 32.4% identical to T. rangeli sialidase.…”

Section: Discussionmentioning

confidence: 68%

Procyclic Trypanosoma brucei Expresses Separate Sialidase and trans-Sialidase Enzymes on Its Surface Membrane

Montagna

Donelson

Frasch

2006

Journal of Biological Chemistry

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The procyclic stage of Trypanosoma brucei in the insect vector expresses a surface-bound trans-sialidase (TbTS) that transfers sialic acid from glycoconjugates in the environment to glycosylphosphatidylinositol-anchored proteins on its surface membrane. RNA interference against TbTS abolished transsialidase activity in procyclic cells but did not diminish sialidase activity, suggesting the presence of a separate sialidase enzyme for hydrolyzing sialic acid. A search of the T. brucei genome sequence revealed seven other putative genes encoding proteins with varying similarity to TbTS. RNA interference directed against one of these proteins, TbSA C, greatly decreased the sialidase activity but had no effect on trans-sialidase activity. The deduced amino acid sequence of TbSA C shares only 40% identity with TbTS but conserves most of the relevant residues required for catalysis. However, the sialidase has a tryptophan substitution for a tyrosine at position 170 that is crucial in binding the terminal galactose that accepts the transferred sialic acid. When this same tryptophan substitution in the sialidase was placed into the recombinant trans-sialidase, the mutant enzyme lost almost all of its trans-sialidase activity and increased its sialidase activity, further confirming that the gene and protein identified correspond to the parasite sialidase. Thus, in contrast to all other trypanosomes analyzed to date that express either a trans-sialidase or a sialidase but not both, T. brucei expresses these two enzymatic activities in two separate proteins. These results suggest that African trypanosomes could regulate the amount of critical sialic acid residues on their surface by modulating differential expression of each of these enzymes.African trypanosomes are protozoan parasites responsible for sleeping sickness in humans and a similar disease in domestic animals called nagana. Their life cycle alternates between the bloodstream of a mammalian host and the tsetse fly vector (Glossina sp.). The surface of the bloodstream form of the parasite is completely covered with 10 7 copies of a single variant surface glycoprotein (VSG) 3 bearing a glycosylphosphatidylinositol (GPI) anchor. These bloodstream trypanosomes elude the immune response of the mammalian host by periodically switching from one VSG to another immunologically distinct VSG. The bloodstream form of the parasite differentiates into the procyclic form when ingested by the insect vector. This differentiation involves a remodeling of the surface in which the VSG coat is rapidly shed and replaced with a new set of invariant GPI-anchored glycoproteins known as procyclins (1). Procyclins have an unusual GPI anchor that, unlike the GPI anchor of VSGs, is decorated with branched poly-N-acetyllactosamine repeats capped by sialic acid residues (2). Trypanosomes are unable to synthesize sialic acid, but the procyclic form of the African trypanosome Trypanosoma brucei expresses a specific enzyme, trans-sialidase (TbTS), that transfers sialic acid from sialylated glyco...

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Section: Discussionmentioning

confidence: 68%

Procyclic Trypanosoma brucei Expresses Separate Sialidase and trans-Sialidase Enzymes on Its Surface Membrane

Montagna

Donelson

Frasch

2006

Journal of Biological Chemistry

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“…T. cruzi transsialidase has also been shown to cause neuronal differentiation, stimulate interleukin-6 secretion from endothelial cells, and potentiate T-cell activation (29,114,138). In the African trypanosomes, trans-sialidase is expressed only in the insect form of the parasite and presumably protects it from gut proteases or complement components of an insect's blood meal (138). The function of the C. diphtheriae trans-sialidase either is unknown or has not been reported.…”

Section: Trans-sialidasementioning

confidence: 99%

“…Endogenous trans-sialidase acceptors are mucin-like molecules that when sialylated may protect bloodstream trypanosomes from innate (antibody-independent) immunity, whereas host cell surface remodeling of glycoproteins facilitates parasite adhesion and invasion (121,122). T. cruzi transsialidase has also been shown to cause neuronal differentiation, stimulate interleukin-6 secretion from endothelial cells, and potentiate T-cell activation (29,114,138). In the African trypanosomes, trans-sialidase is expressed only in the insect form of the parasite and presumably protects it from gut proteases or complement components of an insect's blood meal (138).…”

Section: Trans-sialidasementioning

confidence: 99%

Diversity of Microbial Sialic Acid Metabolism

Vimr

Kalivoda

Deszo

et al. 2004

Microbiol Mol Biol Rev

508

663

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Sialic acids are structurally unique nine-carbon keto sugars occupying the interface between the host and commensal or pathogenic microorganisms. An important function of host sialic acid is to regulate innate immunity, and microbes have evolved various strategies for subverting this process by decorating their surfaces with sialylated oligosaccharides that mimic those of the host. These subversive strategies include a de novo synthetic pathway and at least two truncated pathways that depend on scavenging host-derived intermediates. A fourth strategy involves modification of sialidases so that instead of transferring sialic acid to water (hydrolysis), a second active site is created for binding alternative acceptors. Sialic acids also are excellent sources of carbon, nitrogen, energy, and precursors of cell wall biosynthesis. The catabolic strategies for exploiting host sialic acids as nutritional sources are as diverse as the biosynthetic mechanisms, including examples of horizontal gene transfer and multiple transport systems. Finally, as compounds coating the surfaces of virtually every vertebrate cell, sialic acids provide information about the host environment that, at least in Escherichia coli, is interpreted by the global regulator encoded by nanR. In addition to regulating the catabolism of sialic acids through the nan operon, NanR controls at least two other operons of unknown function and appears to participate in the regulation of type 1 fimbrial phase variation. Sialic acid is, therefore, a host molecule to be copied (molecular mimicry), eaten (nutrition), and interpreted (cell signaling) by diverse metabolic machinery in all major groups of mammalian pathogens and commensals

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“…For trans-sialidases, the nucleophiles are the hydroxyls of carbohydrates. Such enzymes, which occur in pathogenic trypanosomes [40], transfer sialic acids from one glycosidic linkage to the C(3) hydroxyl of a terminal b-linked galactose or N-acetylgalactosamine of oligosaccharides and glycoconjugates. The intramolecular transsialidase (IT-sialidase), found in the leech [36,41], uses as nucleophile the 7-hydroxyl of the same sialic acid molecule, which is released from the glycosidic linkage in this manner.…”

Section: Sialidase and Trans-sialidasementioning

confidence: 99%

Ab initio calculations on various sialic acids provide valuable information about sialic acid-specific enzymes

Lenthe

Boer

Havenith

et al. 2004

Journal of Molecular Structure: THEOCHEM

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This study presents ab initio calculations on six sialic acid derivatives (N-acetylneuraminic acid, 2-deoxy-2,3-didehydro-Nacetylneuraminic acid, N-acetyl-4-O-acetylneuraminic acid, N-glycolylneuraminic acid, N-glycolyl-4-O-acetylneuraminic acid and N-acetyl-9-O-acetylneuraminic acid). The calculations were carried out using the GAMESS-UK-Program. Since the charge distribution of a ligand has an essential impact on the specific interaction with an enzyme or a receptor, the precise results of ab initio calculations lead to significant information concerning possible roles of the different functional groups occurring on sialic acids. In correlation to this, valuable conclusions about the activities of different sialic acid-specific enzymes, such as sialidases, trans-sialidases, lyases and O-acetyl-or O-methyltransferases can be drawn, since these activities strongly depend on the presence or absence of the various functional groups. q 2004 Published by Elsevier B.V.

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Two Trans-sialidase Forms with Different Sialic Acid Transfer and Sialidase Activities from Trypanosoma congolense

Cited by 33 publications

References 54 publications

Procyclic Trypanosoma brucei Expresses Separate Sialidase and trans-Sialidase Enzymes on Its Surface Membrane

Procyclic Trypanosoma brucei Expresses Separate Sialidase and trans-Sialidase Enzymes on Its Surface Membrane

Diversity of Microbial Sialic Acid Metabolism

Ab initio calculations on various sialic acids provide valuable information about sialic acid-specific enzymes

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