g(m1)-ganglioside and Escherichia-coli-Infections

Enteric infections cause more than a billion episodes of diarrhoeal disease in humans each year killing many millions of people, especially young children, in developing countries. Recent progress, reviewed in this article, has enabled that a specific pathogen now can be isolated in the majority of patients with acute diarrhoea, and has also elucidated fundamental pathogenic mechanisms and their pathophysiological effects for several of these agents. Based on this understanding it now seems possible to devise new techniques for the treatment and prevention of diarrhoeal disease to complement those based on fluid replacement therapy and sanitation; prospects for the development of new or improved vaccines, receptor-prophylactic binding agents, and antisecretory drugs are discussed.. Enteric infections cause more than 1 billion episodes of diarrheal disease in humans each year killing many millions of people, especially young children, in developing countries. Recent progress, reviewed here, has enabled that a specific pathogen can now be isolated in the majority of patients with acute diarrhea, and has also elucidated fundamental pathogenic mechanisms and their pathophysiological effects for several of these agents. Based on this understanding, it now seems possible to devise new techniques for the treatment and prevention of diarrheal disease to complement those based on fluid replacement therapy and sanitation. Prospects for the development of new or improved vaccines, receptor-prophylactic binding agents, and antisecretory drugs are discussed.

Topics: Antidiarrheals; Bacterial Vaccines; Calcium; Cholera; Cyclic AMP; Cyclic GMP; Diarrhea; Dysentery, Amebic; Escherichia coli Infections; G(M1) Ganglioside; Humans; Reoviridae Infections; Rotavirus; Viral Vaccines

Enterotoxigenic Escherichia coli (ETEC) is a major cause of illness and death but has no effective therapy. The heat-labile enterotoxin LT is a significant virulence factor produced by ETEC. The heat-labile enterotoxin-B (LT-B) subunit may enter host cells by binding to monosialotetrahexosylganglioside-a (GM1a), a monosialoganglioside found on the plasma membrane surface of animal epithelial cells. This research was conducted to develop conformationally comparable peptides to the carbohydrate epitope of GM1a for the treatment of ETEC. We used the LT-B subunit to select LT-B-binding peptides that structurally resemble GM1a. The ganglioside microarray and docking simulations were used to identify three GM1a ganglioside-binding domain (GBD) peptides based on LT-B recognition. Peptides had an inhibiting effect on the binding of LT-B to GM1a. The binding capacity, functional inhibitory activity, and in vitro effects of the GBD peptides were evaluated using HCT-8 cells, a human intestinal epithelial cell line, to evaluate the feasibility of deploying GBD peptides to combat bacterial infections. KILSYTESMAGKREMVIIT was the most efficient peptide in inhibiting cellular absorption of LT-B in cells. Our findings offer compelling evidence that GM1a GBD-like peptides might act as new therapeutics to inhibit LT-B binding to epithelial cells and avoid the subsequent physiological consequences of LT.

Topics: Animals; Bacterial Toxins; Enterotoxigenic Escherichia coli; Enterotoxins; Escherichia coli Infections; Escherichia coli Proteins; G(M1) Ganglioside; Gangliosides; Humans; Peptides

Guillain-Barré Syndrome (GBS) is a prototype of post-infectious autoimmune disease. A 76-year-old woman was treated for a renal abscess and developed muscle weakness in all four extremities, 18 days after the onset of infection. She was diagnosed with GBS on the basis of acute flaccid paralysis, hyporeflexia, nerve conduction studies (reduced amplitude of compound muscle action potentials), and high titers of IgG antibodies to GM1 and GalNAc-GD1a. GBS rarely occurs after sepsis and this case represents the first report of rapidly progressive GBS following Escherichia coli urosepsis.

Topics: Abscess; Aged; Autoantibodies; Disease Progression; Escherichia coli Infections; Female; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Immunosorbent Techniques; Immunotherapy; Kidney Diseases; Neural Conduction; Paraplegia; Reflex, Abnormal; Time Factors

Serum samples from 43 cases of Guillain-Barré Syndrome (GBS), 32 non-GBS neurology patients, and 35 healthy persons from a medical institute in Kerala, India, were tested for antibody levels against a Campylobacter jejuni strain Penner serotype 0:19 by agglutination and ELISA. Twenty-six percent of samples from GBS cases showed high antibody levels in all assays. Of 8 stool samples of new GBS cases examined by culture, 38% were positive for C. jejuni/C. col1. The results suggest that at least a quarter of GBS cases studied were associated with Campylobacter infection.

Topics: Adolescent; Adult; Antibodies, Bacterial; Autoantibodies; Campylobacter Infections; Campylobacter jejuni; Child; Escherichia coli; Escherichia coli Infections; Feces; Female; G(M1) Ganglioside; Humans; Male; Middle Aged; Polyradiculoneuropathy

A fusion protein, comprising the B subunit of the heat-labile enterotoxin and a portion of the precursor to the heat-stable enterotoxin of Escherichia coli, has been created by recombinant genetic techniques. It is exported successfully to the bacterial periplasm and assembles into pentamers which retain the ability to bind to GM1 ganglioside. Native toxin epitopes are displayed and the molecule can be easily purified from periplasmic extracts of cells expressing the gene fusion. Although the protein carries the natural sequence of the heat-stable enterotoxin, it is greatly attenuated in toxicity. Systemic immunization of mice or oral administration of the fusion elicits antibody responses against both classes of E. coli enterotoxin.

Topics: Administration, Oral; Amino Acid Sequence; Animals; Antibodies, Bacterial; Bacterial Toxins; Bacterial Vaccines; Base Sequence; Diarrhea; Enterotoxins; Escherichia coli Infections; Escherichia coli Proteins; Escherichia coli Vaccines; Female; G(M1) Ganglioside; Injections, Subcutaneous; Mice; Molecular Sequence Data; Protein Precursors; Recombinant Fusion Proteins; Vaccines, Synthetic

A GM1 ganglioside erythroimmunoassay for the detection of heat-labile Escherichia coli enterotoxin (LT) was developed for use in poorly equipped laboratories in developing countries. This assay is based on the immunological similarity between Vibrio cholerae toxin and LT and uses cholera toxin antiserum and sheep anti-rabbit immunoglobulin covalently coupled to sheep erythrocytes as conjugate. This assay has the following advantages over other currently available techniques: the reagents it uses are stable, in particular, tanned and sensitized sheep erythrocytes; GM1 ganglioside is commercially available; erythro-adsorption can be read with the naked eye; the test can be completed in 1 day; and as little as 4 ng of V. cholerae toxin or LT per ml can be detected accurately. The GM1 ganglioside erythroimmunoassay showed good quantitative and qualitative correlation with the Vero cell assay and the conventional GM1 enzyme-linked immunosorbent assay. The GM1 ganglioside erythroimmunoassay was somewhat less sensitive than the GM1 enzyme-linked immunosorbent assay but more sensitive than the Vero cell assay. Results obtained for 12 LT-positive and 138 LT-negative E. coli strains correlated with results obtained with GM1 enzyme-linked immunosorbent and Vero cell assays.

Topics: Animals; Bacterial Toxins; Cholera Toxin; Enterotoxins; Erythrocytes; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; G(M1) Ganglioside; Humans; Immunoassay; Sheep

A ganglioside enzyme-linked immunosorbent assay (ELISA) was used to study and attempt to differentiate between antitoxin responses in persons infected with either Vibrio cholerae or Escherichia coli producing heat-labile enterotoxin. In most cases (69%-94%), experimentally infected North Americans and naturally infected Bangladeshis responded to either infection with significant (greater than twofold) increases in serum antibody titer to both heat-labile enterotoxin and cholera toxin. In all but one instance, the response was higher to the homologous than to the heterologous toxin, and for the Americans the homologous antitoxin titers remained significantly higher for at least one year. Determination of levels of antibodies to purified subunits A and B of cholera toxin by an ELISA showed that V. cholerae infection in most instances induced a significant response to subunit B but rarely to subunit A. E. coli infection, on the other hand, induced only slight increases in antibody titer to either subunit.

Topics: Adolescent; Adult; Aged; Antibodies, Bacterial; Antitoxins; Bacterial Toxins; Bangladesh; Child; Child, Preschool; Cholera; Cholera Toxin; Enterotoxins; Enzyme-Linked Immunosorbent Assay; Escherichia coli Infections; Escherichia coli Proteins; Female; G(M1) Ganglioside; Humans; Infant; Male; Middle Aged; North America