epiglucan and Escherichia-coli-Infections

The effect of orally administered beta-glucans in protecting pigs against an ETEC infection after weaning was analysed in this study. Three beta-glucans that differed in origin (Saccharomyces cerevisiae (MCG (Macrogard) and G2) or Sclerotium rolfsii (G3)) and/or extraction procedure were tested. Pigs fed for 2 weeks after weaning with these glucans were less susceptible to an F4+ ETEC infection in comparison with the control group. This was evidenced by a reduction in the faecal excretion of F4+ Escherichia coli as well as a reduced F4-specific serum antibody response. This decrease in faecal excretion was statistically significant for pigs fed with the MCG glucan in a first experiment and with the G3 glucan in a second experiment; diarrhoea was milder in the glucan-supplemented groups and was significantly reduced in the MCG-supplemented group. Furthermore, a lower amount of F4-specific IgM antibody-secreting cells (ASC) was found in the lymphoid tissues of pigs fed with G2 or G3 glucans in comparison with the control pig, as well as lower F4-specific IgA ASC in G3-fed pigs in comparison with the control pig. This study showed that beta-glucans can protect against an ETEC infection. Both MCG from S. cerevisiae and G3 from S. rolfsii, resulted in significant effects. To our knowledge, this is the first in vivo study, in which the use of beta-glucans as feed ingredient for just-weaned piglets was tested for their protective effects against ETEC infection.

Topics: Animal Feed; Animals; beta-Glucans; Diarrhea; Diet; Dietary Supplements; Enterotoxigenic Escherichia coli; Escherichia coli Infections; Immunoglobulins; Swine; Swine Diseases; Weaning

The development of antibiotic-resistant bacteria has led to a need for alternatives to antibiotics for growth promotion and disease prevention in poultry production. The helical polysaccharide beta-1,3/1,6-glucan is derived from the cell wall of Saccharomyces cervisiae and has immunomodulating activities. The objective of this study was to determine the ability of 2 supplementation programs with a commercial beta-1,3/1,6-glucan product to protect broiler chicks from experimental respiratory challenge with Escherichia coli. Chicks were housed in battery-brooders from 1 d of age and fed a standard starter diet or the same diet containing 20 g/ton (22 ppm) of purified beta-1,3/1,6-glucan either continuously (BG25d) or for only the first 7 d prior to challenge (BG7d). At d 7 one-half of the birds were inoculated in the thoracic air sac with 800 cfu of a serotype O2, nonmotile strain of E. coli. All surviving birds were necropsied at d 25. Body weight of survivors and feed conversion efficiency were protected from the adverse effects of E. coli challenge by BG7d but not by BG25d. Mortality was nominally decreased from 63% (control) to 53% in BG25d and 47% in BG7d, but these decreases were not significant. The relative weights of the liver and heart were increased, and the bursa of Fabricius relative weights were decreased by E. coli challenge, and these effects were modulated by beta-glucan treatment. Despite positive effects of BG7d in E. coli-challenged birds, the BW of nonchallenged birds was decreased by BG7d and BG25d. These results suggest that supplementation of broiler diets with beta-1,3/1,6-glucan may be valuable for decreasing production losses due to E. coli respiratory disease, but that the immune stimulation provided may also result in decreased production values under experimental battery conditions or for birds raised in an environment with minimal disease challenges.

Topics: Animals; Chickens; Escherichia coli Infections; Female; Glucans; Male; Poultry Diseases

To explore the protective effect of dietary β-glucan (BGL) supplementation on intestinal epithelium exposure to enterotoxigenic Escherichia coli (ETEC), thirty-two weaned pigs were assigned to four groups. Pigs were fed with a basal diet or basal diet containing 500 mg/kg BGL, and were orally infused with ETEC or culture medium. Results showed BGL supplementation had no influence on growth performance in weaned pigs. However, BGL supplementation increased the absorption of D-xylose, and significantly decreased the serum concentrations of D-lactate and diamine oxidase (DAO) in the ETEC-challenged pigs (p < 0.05). Interestingly, BGL significantly increased the abundance of the zonula occludens-1-(ZO-1) in the jejunal epithelium upon ETEC challenge (p < 0.05). BGL supplementation also increased the number of S-phase cells and the number of sIgA-positive cells, but significantly decreased the number of total apoptotic cells in the jejunal epithelium upon ETEC challenge (p < 0.05). Moreover, BGL significantly increased the duodenal catalase (CAT) activity and the ileal total superoxide dismutase (T-SOD) activity in the ETEC-challenged pigs (p < 0.05). Importantly, BGL significantly decreased the expression levels of critical inflammation related proteins such as the tumor necrosis factor-α (TNF-α), interlukin-6 (IL-6), myeloid differentiation factor 88 (MyD88), and nuclear factor-κB (NF-κB) in the jejunal and ileal mucosa upon ETEC challenge (p < 0.05). BGL also elevated the propanoic acid content and the abundance of Lactobacillus and Bacillus in the colon upon ETEC challenge (p < 0.05). These results suggested BGL could alleviate the ETEC-induced intestinal epithelium injury, which may be associated with suppressed inflammation and improved intestinal immunity and antioxidant capacity, as well as the improved intestinal macrobiotic.

Topics: Agrobacterium; Amine Oxidase (Copper-Containing); Animals; Antioxidants; beta-Glucans; Catalase; Enterotoxigenic Escherichia coli; Escherichia coli Infections; Immunoglobulin A, Secretory; Inflammation; Interleukin-6; Intestinal Mucosa; Lactates; Myeloid Differentiation Factor 88; NF-kappa B; Propionates; Superoxide Dismutase; Swine; Swine Diseases; Tumor Necrosis Factor-alpha; Xylose

Results indicated significant alteration of growth performance, serum biochemistry, and selected liver gene expression with pathological lesions, especially in the lymphoid organs due to E. coli infection. These alterations were mitigated by Mannan-oligosaccharide and β-Glucan supplementation.. It could be concluded, Mannan-oligosaccharide and β-Glucan supplementation in broiler's diet improved the immune response of broilers and mitigated pathological lesion resulted from E. coli infection.

Topics: Animal Feed; Animals; beta-Glucans; Chickens; Diet; Escherichia coli; Escherichia coli Infections; Female; Liver; Male; Mannans; NF-kappa B; Poultry Diseases; Probiotics; Tumor Necrosis Factor-alpha

Systemic infections caused by extraintestinal pathogenic Escherichia coli (ExPEC) have emerged as the most common community-onset bacterial infections and are major causes of nosocomial infections worldwide. The management of ExPEC infections has been complicated by the heterogeneity of ExPEC strains and the emergence of antibiotic resistance, thus their prevention through vaccination would be beneficial. The protective efficacy of four common ExPEC antigen candidates composed of common pilus antigens EcpA and EcpD and iron uptake proteins IutA and IroN, were tested by both active and passive immunization in lethal and non-lethal murine models of sepsis. Additionally, antibody raised to a synthetic form of a conserved surface polysaccharide, β-(1-6)-linked poly-N-acetylglucosamine (dPNAG) containing 9 monomers of (non-acetylated) glucosamine (9GlcNH2) conjugated to tetanus toxoid TT (9GlcNH2-TT) was tested in passive immunization protocols. Active immunization of mice with recombinant antigens EcpA, EcpD, IutA, or IroN elicited high levels of total IgG antibody of IgG1/IgG2a isotypes, and were determined to be highly protective against E. coli infection in lethal and non-lethal sepsis challenges. Moreover, passive immunization against these four antigens resulted in significant reductions of bacteria in internal organs and blood of the mice, especially when the challenge strain was grown in iron-restricted media. Inclusion of antibodies to PNAG increased the efficacy of the passive immunization under conditions where the challenge bacteria were grown in LB medium but not in iron-restricted media. The information and data presented are the first step toward the development of a broadly protective vaccine against sepsis-causing E. coli strains.

Topics: Animals; Antibodies, Bacterial; Antigens, Bacterial; beta-Glucans; Escherichia coli Infections; Escherichia coli Proteins; Escherichia coli Vaccines; Female; Fimbriae Proteins; Immunization, Passive; Immunoglobulin G; Mice; Molecular Chaperones; Rabbits; Receptors, Cell Surface; Sepsis; Vaccines, Conjugate

Many pathogens produce the β-(1-6)-linked poly-N-acetylglucosamine (PNAG) surface polysaccharide that is being developed as a broadly protective antimicrobial vaccine. However, it is unknown whether systemically injected PNAG vaccines or antibodies would provide protective immunity against pathogens confined to the gastrointestinal tract such as Shiga toxin (Stx)-producing Escherichia coli (STEC), an important group of gastrointestinal (GI) pathogens for which effective immunotherapeutics are lacking. To ascertain whether systemic IgG antibody to PNAG impacts this infectious situation, a vaccine consisting of a synthetic nonamer of nonacetylated PNAG, 9GlcNH2, conjugated to the Shiga toxin 1b subunit (9GlcNH2-Stx1b) was produced. Rabbit antibodies raised to the conjugate vaccine were tested for bacterial killing and toxin neutralization in vitro and protection against infection in infant mice. Cell surface PNAG was detected on all 9 STEC isolates tested, representing 6 STEC serogroups, including E. coli O157:H7. Antibody to the 9GlcNH2-Stx1b conjugate neutralized Stx1 potently and Stx2 modestly. For O157:H7 and O104:H4 STEC strains, antibodies elicited by the 9GlcNH2-Stx1b conjugate possessed opsonic killing and bactericidal activity. Following intraperitoneal injection, antibodies to both PNAG and Stx were needed for infant mouse protection against O157 STEC. These antibodies also mediated protection against the Stx2-producing O104:H4 strain that was the cause of a recent outbreak in Germany, although sufficient doses of antibody to PNAG alone were protective against this strain in infant mice. Our observations suggest that vaccination against both PNAG and Stx, using a construct such as the 9GlcNH2-Stx1b conjugate vaccine, would be protective against a broad range of STEC serogroups. IMPORTANCE The presence of poly-N-acetylglucosamine (PNAG) on many pathogens presents an opportunity to target this one structure with a multispecies vaccine. Whether antibodies to PNAG can protect against pathogens confined to the gastrointestinal tract is not known. As Shiga toxin (Stx)-producing Escherichia coli (STEC) bacteria are serious causes of infection whose virulence is dependent on elaboration of Stx, we prepared a vaccine containing a synthetic nonamer of PNAG (9GlcNH2) conjugated to Shiga toxin 1b subunit (9GlcNH2-Stx1b) to evaluate bacterial killing, toxin neutralization, and protective efficacy in infant mice. All nine (100%) clinical strains of STEC from di

Topics: Animals; Animals, Newborn; Antibodies, Bacterial; Antibodies, Neutralizing; Antitoxins; beta-Glucans; Disease Models, Animal; Escherichia coli Infections; Escherichia coli Vaccines; Mice; Microbial Viability; Opsonin Proteins; Rabbits; Shiga Toxin; Shiga-Toxigenic Escherichia coli; Vaccines, Conjugate

Vaccines for pathogens usually target strain-specific surface antigens or toxins, and rarely is there broad antigenic specificity extending across multiple species. Protective antibodies for bacteria are usually specific for surface or capsular antigens. beta-(1-->6)-Poly-N-acetyl-d-glucosamine (PNAG) is a surface polysaccharide produced by many pathogens, including Staphylococcus aureus, Escherichia coli, Yersinia pestis, Bordetella pertussis, Acinetobacter baumannii, and others. Protective antibodies to PNAG are elicited when a deacetylated glycoform (deacetylated PNAG [dPNAG]; <30% acetate) is used in conjugate vaccines, whereas highly acetylated PNAG does not induce such antibodies. Chemical derivation of dPNAG from native PNAG is imprecise, so we synthesized both beta-(1-->6)-d-glucosamine (GlcNH(2)) and beta-(1-->6)-d-N-acetylglucosamine (GlcNAc) oligosaccharides with linkers on the reducing termini that could be activated to produce sulfhydryl groups for conjugation to bromoacetyl groups introduced onto carrier proteins. Synthetic 5-mer GlcNH(2) (5GlcNH(2)) or 9GlcNH(2) conjugated to tetanus toxoid (TT) elicited mouse antibodies that mediated opsonic killing of multiple S. aureus strains, while the antibodies that were produced in response to 5GlcNAc- or 9GlcNAc-TT did not mediate opsonic killing. Rabbit antibodies to 9GlcNH(2)-TT bound to PNAG and dPNAG antigens, mediated killing of S. aureus and E. coli, and protected against S. aureus skin abscesses and lethal E. coli peritonitis. Chemical synthesis of a series of oligoglucosamine ligands with defined differences in N acetylation allowed us to identify a conjugate vaccine formulation that generated protective immune responses to two of the most challenging bacterial pathogens. This vaccine could potentially be used to engender protective immunity to the broad range of pathogens that produce surface PNAG.

Topics: Acetylation; Animals; Antibodies, Bacterial; Bacterial Capsules; beta-Glucans; Enzyme-Linked Immunosorbent Assay; Escherichia coli Infections; Humans; Mice; Peritonitis; Rabbits; Staphylococcal Skin Infections; Vaccines, Conjugate

The results of translam chemical structure and biological activity investigation are presented. Translam is a new original semisynthetic polysaccharide of marine origin. The preparation demonstrated potent treatment effect in experimental radiation disease. It had preventing effect at experimental bacterial infections, stimulated hematopoiesis, had effect on humoral and cell immunity and on factors of nonspecific organism resistance.

Topics: Acute Disease; Adjuvants, Immunologic; Animals; Antibody-Producing Cells; Cells, Cultured; Dogs; Escherichia coli Infections; Glucans; Guinea Pigs; Hematopoiesis; Hypersensitivity, Delayed; Macrophages; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Phagocytosis; Radiation Injuries, Experimental; Yersinia pseudotuberculosis Infections

Effect of translam--beta-1,3;1,6-D-glucan on some of naturally occurring host protective mechanisms was investigated. It was shown that translam has potent biological activity: it has preventive effect on experimental bacterial infections, it stimulates absorbtion and digestion activity of mononuclear phagocytes, it effects on humoral and cell immunity. Translam had mitogenic activity.

Topics: Adjuvants, Immunologic; Animals; Antibody Formation; Cells, Cultured; Drug Evaluation, Preclinical; Escherichia coli Infections; Glucans; Guinea Pigs; Immunity, Cellular; Laminaria; Macrophages; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Mitogens; Spleen; Yersinia pseudotuberculosis Infections

It is demonstrated that the biological effects of the immunomodulator beta 1-3D polyglucose, when covalently linked to polymethacrylate or biodegradable albumin microbeads, are strongly potentiated. The potentiation is recorded as an increased protection effect of the conjugates in Escherichia coli sepsis in mice, and as increased IL-1 production by murine macrophages in vitro.

Topics: Adjuvants, Immunologic; Animals; beta-Glucans; Biocompatible Materials; Biotransformation; Drug Synergism; Escherichia coli Infections; Female; Glucans; Immunologic Factors; Interleukin-1; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Microspheres

The emergence of multiple antibiotic-resistant microorganisms has led to a search for alternatives to traditional therapeutic regimens. PGG glucan is a soluble beta-glucan immunomodulator that selectively enhances the microbicidal activities of neutrophils and macrophages without stimulating proinflammatory cytokine production. In the present studies, we examined the ability of PGG glucan to act in concert with antibiotics to decrease mortality in a rat model of intraabdominal sepsis using antibiotic-resistant bacteria as infectious inocula. Results of these studies demonstrated that prophylaxis with PGG glucan in combination with antibiotics provided enhanced protection against lethal challenge with Esherichia coli or Staphylococcus aureus as compared with the use of antibiotics alone.

Topics: Adjuvants, Immunologic; Animals; Anti-Bacterial Agents; beta-Glucans; Drug Resistance, Microbial; Drug Therapy, Combination; Escherichia coli; Escherichia coli Infections; Glucans; Rats; Sepsis; Staphylococcal Infections; Staphylococcus aureus

In order to correctly diagnose and treat severe postoperative infections, it may be critical to detect and differentiate between endotoxin derived from Gram-negative bacteria and/or beta-glucan derived from fungi. In addition to the chromogenic assay, the turbidimetric kinetic assay has been performed for the quantification of endotoxin in plasma using Limulus amebocyte lysate as previously reported. However, it is also known that beta-glucan triggers the coagulation of Limulus amebocyte lysate. In the present study, the differentiation of beta-glucan from endotoxin and its clinical application were studied. Endotoxin was able to be inactivated in plasma using one-tenth dilution by 10 per cent ethanol or distilled water, followed by heating at 100 degrees C for 120 min, without affecting the activity of coexisting beta-glucan. The treated sample was then subjected to the turbidimetric kinetic assay using Toxinometer ET-201. Using this method, as little as 30 pg/ml of beta-glucan in the plasma may be assayed separately, with the amount of circulating beta-glucan in the plasma of normal subjects being less than 50 pg/ml. On the other hand, in patients with a fungal infection, the amount of beta-glucan in their plasma was elevated significantly. Clinically, beta-glucanemia may often occur in severe postoperative infection even if fungi are not detected.

Topics: beta-Glucans; Candidiasis; Endotoxins; Escherichia coli Infections; Glucans; Humans; Mycoses; Pseudomonas aeruginosa; Pseudomonas Infections; Reference Values; Salmonella Infections; Surgical Wound Infection

The influences of pretreatment with beta-1,3-D-polyglucose derivatives on levels of cytokines and arachidonic acid metabolites in body fluids in experimental peritonitis in mice are reported. Peritonitis was induced by an intraperitoneal injection of 10(8) live Escherichia coli. Pretreated animals survived the infection, untreated animals died about 12 h after inoculation with E. coli. Levels of IL-1 in plasma and peritoneal fluid, measured by cytotoxicity assay of the HT-2 cell line, increased significantly during the first 48 h after intraperitoneal treatment with beta-1,3-D-polyglucose-derivatized microbeads (GDM) or soluble, aminated beta-1,3-D-polyglucose (AG). After subsequent challenge with E. coli, the levels of IL-1 were significantly lower than in untreated animals. There was no increase in levels of TNF after treatment with GDM or AG, measured by cytotoxicity assay of the WEHI clone 13 cell line. After challenge with E. coli, TNF in plasma and peritoneal fluid was significantly lower compared with untreated animals. Both PGE2 and LTB4, measured by radioimmunoassay kits, were increased in peritoneal fluid after treatment with GDM and AG. After challenge with E. coli, PGE2 and LTB4 in peritoneal fluid increased to about half the concentration of infected control animals. Intraperitoneal injection of indomethacin to pretreated animals resulted in increased levels of IL-1 and TNF and decreased levels of PGE2 following challenge with E. coli. The levels of IL-1 and TNF remained elevated until the animals died after about 12 h. These studies demonstrate that the raised levels of arachidonic acid metabolites after pretreatment with GDM or AG seem to inhibit the otherwise lethal elevation of IL-1 and TNF in body fluids which is seen in untreated animals.

Topics: Animals; Arachidonic Acids; Ascitic Fluid; beta-Glucans; Cytokines; Dinoprostone; Escherichia coli Infections; Female; Glucans; Indomethacin; Interleukin-1; Leukocyte Count; Leukotriene B4; Mice; Mice, Inbred CBA; Sepsis; Tumor Necrosis Factor-alpha

Beta-1,3-D-polyglucose derivatives protect mice against otherwise lethal bacterial infections. This protective effect has previously been considered to be mediated through mononuclear phagocytes. We have now investigated the cellular composition in blood and peritoneal fluid after administration of the beta-1,3-D-polyglucose before and after challenge with Escherichia coli. In animals treated with beta-1,3-D-polyglucose derivatives, the total white cell number was significantly increased in both blood and peritoneal fluid before and after challenge with E. coli. The increased total cell number was mainly the result of raised levels of granulocytes. The effects of beta-1,3-D-polyglucose-derivatized microbeads (GDM) and soluble aminated beta-1,3-D-polyglucose (AG) were similar. Bacterial counts in peripheral blood in GDM- and AG-treated animals increased with 6 h after challenge and approached zero after 24 h. In untreated animals the bacterial counts increased gradually until the animals died after about 12 h. Bacterial counts in peritoneal fluid of GDM- and AG-treated animals declined to zero after 24 h. In untreated animals there was a slight increase in bacterial counts until the animals died after about 12 h. By using radioactive labelling, we localized the bacterial as well as the beta-1,3-D-polyglucose derivatives during the period following injection. Particle-bound beta-1,3-D-polyglucose was recovered mainly in the milky spots of the omentum. A conspicuous number of bacteria were also recovered in the milky spots. The soluble aminated beta-1,3-D-polyglucose was recovered mainly in the liver. However, on a weight basis, the greatest concentration of radioactivity was in the milky spots.

Topics: Animals; Ascitic Fluid; beta-Glucans; Colony Count, Microbial; Escherichia coli Infections; Female; Glucans; Immunity, Innate; Leukocyte Count; Mice; Mice, Inbred C3H; Mice, Inbred CBA; Microspheres; Omentum; Peritoneal Diseases; Sepsis

Pretreatment with beta-1,3-D-glucan-derivatized plastic beads conferred strong protection against Escherichia coli infection in mice. The protective effect showed a dose-response relationship to the amount of beads injected and was dependent on the time point of the injection relative to the infection with E. coli. A similar protection could be obtained in nude mice. Experiments with radioactively labelled bacteria as well as beads indicated a systemic effect of the beads. Macrophages extracted from animals treated with glucan plastic beads appeared highly stimulated. This was also true of cells that did not contain beads and presumably therefore not glucan, which seems to indicate a soluble stimulatory factor.

Topics: Animals; beta-Glucans; Escherichia coli Infections; Female; Glucans; Injections, Intraperitoneal; Macrophage Activation; Mice; Mice, Inbred C3H; Mice, Inbred DBA; Mice, Nude; Microspheres; Tissue Distribution