Mammalian cell ganglioside-binding specificities of E. coli enterotoxins LT-IIb and variant LT-IIb(T13I)

Berenson, Charles S.; Nawar, Hesham F.; Yohe, Herbert C.; Castle, Sherry A.; Ashline, David J.; Reinhold, Vernon N.; Hajishengallis, George; Connell, Terry D.

doi:10.1093/glycob/cwp141

Cited by 21 publications

(42 citation statements)

References 42 publications

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“…Binding of LT-IIa, LT-IIb, and CT to different cell types is mediated by the enterotoxins' capacities to interact and avidly bind to different gangliosides (1,9). Each of the HLTs binds to a different array of gangliosides (5,6).…”

Section: Vol 78 2010 Lt-iic a New Type II Heat-labile Enterotoxin mentioning

confidence: 99%

LT-IIc, a New Member of the Type II Heat-Labile Enterotoxin Family Encoded by an Escherichia coli Strain Obtained from a Nonmammalian Host

Nawar

King-Lyons

et al. 2010

Infect Immun

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Infections caused by enterotoxigenic Escherichia coli (ETEC)are the leading cause of traveler's diarrhea and the major cause of diarrheal disease in underdeveloped nations, especially among children. ETEC, which is usually transmitted by food or water contaminated with animal or human feces, is estimated to be responsible annually for more than 650 million cases of enteric infections and nearly 800,000 deaths (29). Infection begins with ingestion of bacteria, followed by elaboration of enterotoxin and bacterial colonization of the gut, and presents as a profuse watery diarrhea which disseminates the bacteria back into the environment (10).ETEC strains are lactose-fermenting E. coli strains that produce a heat-labile enterotoxin (LT, hereafter referred to as LT-I), heat-stable enterotoxins (ST), or both and colonization factors which enable ETEC to colonize the small intestine (22). The pathogenesis of ETEC is dependent on the strains' capacity to produce LT-I and/or ST (10, 29). LT-I is closely related functionally, antigenically, and structurally to cholera toxin (CT), the heat-labile enterotoxin produced by Vibrio cholerae. Antiserum against CT neutralizes the toxicity of LT-I, and antiserum against LT-I neutralizes the toxicity of CT (15). Structurally, LT-I and CT are oligomeric proteins composed of an A polypeptide which is noncovalently coupled to a pentameric array of B polypeptides (15). The A polypeptide of LT-I and CT is enzymatically active and catalyzes an ADP-ribosylation of the G s ␣ regulatory protein in the intoxicated cell. Ribosylation of this regulatory protein constitutively activates adenylate cyclase, the enzyme which catalyzes production of cyclic AMP (cAMP) (3,20). Accumulation of cAMP induces the intoxicated cell to secrete electrolytes and chloride ions, thus generating the watery diarrhea, which is symptomatic of intoxication. Intracellular accumulation of cAMP modulates other cellular processes such as protein kinase activity, activation of calcium channels, etc. (15). Binding of LT-I and CT to ganglioside receptors is mediated by the B polypeptides. Gangliosides are members of a heterogeneous family of sialylated glycosphingolipids expressed on the surface of eukaryotic cells (9). Based on these characteristics, LT-I and CT have been designated as members of the large family of toxins known as the A 1 B 5 ADP-ribosylating heat-labile enterotoxins (HLTs).LT-IIa and LT-IIb, two new members of the A 1 B 5 family of HLTs produced by E. coli, were recently described (11,12,27). While it is clear that LT-IIa and LT-IIb are evolutionarily related to LT-I and CT, there are major differences between the two groups of enterotoxins. LT-IIa and LT-IIb are antigenically distinguishable from LT-I and CT and from each other (12). These antigenic differences are reflected in the low amino acid sequence similarity of the A polypeptides and the virtual absence of amino acid sequence homology of the B polypeptides between the two groups (LT-I and CT versus LT-IIa and LT-IIb) (35). To distinguish betwee...

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Section: Vol 78 2010 Lt-iic a New Type II Heat-labile Enterotoxin mentioning

confidence: 99%

LT-IIc, a New Member of the Type II Heat-Labile Enterotoxin Family Encoded by an Escherichia coli Strain Obtained from a Nonmammalian Host

Nawar

King-Lyons

et al. 2010

Infect Immun

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“…Gangliosides were isolated from peritoneal macrophages obtained from thioglycolate-treated C57BL/6J or Cmah-null mice (5,6).…”

Section: Methodsmentioning

confidence: 99%

“…Two-dimensional (2-D) thin-layer chromatography (TLC) was used to resolve gangliosides (5). Standard ganglioside markers (Matreya, LLC) were included in each dimension for reference.…”

Section: Methodsmentioning

confidence: 99%

“…Using thin-layer chromatography (TLC) and immunoblotting methods, the ganglioside receptors for LT-IIb and LT-IIb(T13I) on RAW 264.7 cells and on murine peritoneal macrophages were identified (5). These experiments revealed that LT-IIb had binding affinity for a broader range of gangliosides than had been reported previously (5,17). Moreover, LT-IIb(T13I) was shown to have preferential binding for NeuGc gangliosides while exhibiting diminished binding activity for NeuAc gangliosides (5).…”

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confidence: 86%

“…It was clear, therefore, that LT-IIb(T13I) interacted with one or more unknown receptors on those cells and that, in macrophages, those receptors had chemical characteristics compatible with a ganglioside (5). Using thin-layer chromatography (TLC) and immunoblotting methods, the ganglioside receptors for LT-IIb and LT-IIb(T13I) on RAW 264.7 cells and on murine peritoneal macrophages were identified (5). These experiments revealed that LT-IIb had binding affinity for a broader range of gangliosides than had been reported previously (5,17).…”

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confidence: 99%

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Binding to Gangliosides Containing N -Acetylneuraminic Acid Is Sufficient To Mediate the Immunomodulatory Properties of the Nontoxic Mucosal Adjuvant LT-IIb(T13I)

Nawar

Berenson

Hajishengallis

et al. 2010

Clin Vaccine Immunol

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Mucosal vaccines consisting solely of protein antigens (Ag) routinely induce only weak immune responses or tolerance at mucosal surfaces (50). Thus, to generate robust and long-lived immune responses to Ag at mucosal sites, an immune-stimulating agent(s) must be added to mucosal vaccines. These immune-stimulating agents are commonly referred to as mucosal adjuvants.The strongest mucosal adjuvants described are members of the family of bacterial heat-labile enterotoxins (HLTs). This family is divided into two major groups based on genetic, biochemical, and immunological characteristics (25). A number of heat-labile enterotoxins are members of the type I HLT subfamily; these include cholera toxin (CT), produced by Vibrio cholerae, and LT (referred to below as LT-I), produced by Escherichia coli (25).

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Investigation of substrate specificity of sialidases with membrane mimetic glycoconjugates

Tomar

Sun

2019

Glycoconj J

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Mammalian cell ganglioside-binding specificities of E. coli enterotoxins LT-IIb and variant LT-IIb(T13I)

Cited by 21 publications

References 42 publications

LT-IIc, a New Member of the Type II Heat-Labile Enterotoxin Family Encoded by an Escherichia coli Strain Obtained from a Nonmammalian Host

LT-IIc, a New Member of the Type II Heat-Labile Enterotoxin Family Encoded by an Escherichia coli Strain Obtained from a Nonmammalian Host

Binding to Gangliosides Containing N -Acetylneuraminic Acid Is Sufficient To Mediate the Immunomodulatory Properties of the Nontoxic Mucosal Adjuvant LT-IIb(T13I)

Investigation of substrate specificity of sialidases with membrane mimetic glycoconjugates

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