epiglucan and Bacterial-Infections

Poly-β-(1→6)-N-acetylglucosamine (PNAG) was first discovered as a major component of biofilms formed by Staphylococcus aureus and some other staphylococci but later this exopolysaccharide was also found to be produced by pathogens of various nature. This common antigen is considered as a promising target for construction of a broadly protective vaccine. Extensive studies of PNAG, its de-N-acetylated derivative (dPNAG, containing around 15% of residual N-acetates) and their conjugates with Tetanus Toxoid (TT) revealed the crucial role of de-N-acetylated glucosamine units for the induction of protective immunity. Conjugates of synthetic penta- (5GlcNH

Topics: Animals; Bacterial Infections; Bacterial Vaccines; beta-Glucans; Disease Models, Animal; Glycoconjugates; Humans; Immunogenicity, Vaccine; Polysaccharides, Bacterial; Tetanus Toxoid; Vaccines, Synthetic

Recent studies have shown that naturally occurring substances found in the food of the daily human diet are important for preventing chronic non-communicable diseases. One of them is beta-glucan, which is a natural polysaccharide, occurring in plant cell walls, mainly oats, barley and wheat. It is also present in baker’s yeast cells, fungal cell walls, and some microorganisms. Beta-glucan belongs to one of the dietary fiber fractions, which are attributed a number of beneficial health properties, including the prevention and treatment of certain digestive diseases and supporting the immune system. This compound has biological activity that depends on the size, molecular weight, conformation, frequency of bonds, solubility and changes in structure. Beta-glucan reduces cholesterol and glucose concentrations in the blood, which reduces the risk of cardiovascular disease and diabetes. In addition to its effects on lipid levels and glucose metabolism, beta-glucan also exhibits antioxidant properties by scavenging reactive oxygen species, thereby reducing the risk of diseases, including atherosclerosis, cardiovascular diseases, neurodegenerative diseases, diabetes, and cancer. Immunostimulatory and antitumor effects have also been reported. The immunostimulatory activity of beta-glucan occurs as a result of its attachment to specific receptors present on the immune cell surface. Beta-glucan belongs to the group of prebiotics which stimulate the growth and activity of the desired natural intestinal microbiota, while inhibiting the growth of pathogens. It plays an important role in the proper functioning of the gastrointestinal tract and preventing inflammation as well as colon cancer. Such a number of health benefits resulting from the properties of beta-glucan may play a key role in improving health and preventing chronic non-communicable diseases, such as diabetes, hypercholesterolemia, obesity, cardiovascular diseases, and cancer.

Topics: Bacterial Infections; beta-Glucans; Blood Glucose; Diabetes Mellitus, Type 2; Dietary Fiber; Heart Diseases; Humans; Immune System; Insulin; Nutritional Physiological Phenomena; Reactive Oxygen Species

Sepsis is a life-threatening response to systemic infection. In addition to frank gastrointestinal (GI) rupture/puncture, sepsis can also be exacerbated by translocation of pathogen-associated molecular patterns (PAMPs) from the GI tract to the systemic circulation (gut origin of sepsis). In the human gut, Gram-negative bacteria and Candida albicans are abundant, along with their major PAMP components, endotoxin (LPS) and (1 → 3)-β-D-glucan (BG). Whereas the influence of LPS in bacterial sepsis has been studied extensively, exploration of the role of BG in bacterial sepsis is limited. Post-translocation, PAMPs enter the circulation through lymphatics and the portal vein, and are detoxified and then excreted via the liver and the kidney. Sepsis-induced liver and kidney injury might therefore affect the kinetics and increase circulating PAMPs. In this article, we discuss the current knowledge of the impact of PAMPs from both gut mycobiota and microbiota, including epithelial barrier function and the "gut-liver-kidney axis," on bacterial sepsis severity.

Topics: Animals; Bacterial Infections; beta-Glucans; Candida; Gastrointestinal Tract; Humans; Intestinal Mucosa; Kidney; Lipopolysaccharides; Liver; Pathogen-Associated Molecular Pattern Molecules; Proteoglycans; Sepsis

β-glucans are known for their immune-modulating properties. However, the heterogeneity of these glucose polymers makes a distinction between the different sources and structures necessary-a fact that has been little allowed for in the literature. We have focused on β-glucans from cereals as they are already used as functional food ingredients due to their established cholesterol lowering effect. Cereal β-glucans have shown in vitro activity on cytokine secretion, phagocytic activity and cytotoxicity of isolated immune cells, and activation of the complement system. Animal studies suggest a possible protective effect against an intestinal parasite, against bacterial infection, and a synergistic effect in antibody-dependent cellular cytotoxicity. Animal studies have shown activity of orally applied cereal β-glucans indicating uptake or interaction with cells of the gastrointestinal tract. However, uptake is still debated, interaction with intestinal epithelial cells has been suggested but not clarified, and mechanisms of action remain largely unknown. So far, cereal β-glucans have not shown immune modulation in the few conducted human studies and further studies are needed to clarify their effect.

Topics: Animals; Anti-Bacterial Agents; Antineoplastic Agents; Bacterial Infections; beta-Glucans; Edible Grain; Humans; Immunologic Factors; Intestinal Diseases, Parasitic; Intestines

In our current world, antibiotic resistance among pathogenic microbes keeps getting worse with few new antibiotics being pursued by pharmaceutical companies. Modern-day immunotherapies, reminiscent of the serotherapy approaches used in the early days of antimicrobial treatments, are a potential counter-measure, but are usually limited by the narrow spectrum against target antigens. Surprisingly, many multidrug-resistant (MDR) bacteria share a common surface polysaccharide, poly-β-1,6-N-acetylglucosamine (PNAG). Natural antibodies to PNAG are present in normal human sera, but are not protective. However, human monoclonal antibodies (MAbs) or polyclonal antisera raised to a deacetylated glycoform of PNAG mediate opsonic killing and protect mice against infections due to all PNAG-positive MDR pathogens tested. An MAb is currently in Phase II clinical trials. These discoveries could lead to utilization of antibodies to PNAG for either therapeutic use in patients infected by PNAG-producing MDR bacteria or prophylactic use in patients at risk of developing MDR infections.

Topics: Animals; Antibodies, Bacterial; Antibodies, Monoclonal; Bacteria; Bacterial Infections; beta-Glucans; Clinical Trials as Topic; Disease Models, Animal; Humans; Immunotherapy; Treatment Outcome

This review summarizes the recent knowledge about the positive effect of betaglucans on human health. Beta-glucans are polysaccharides occurring in the bran of cereal grains (barley and oats and to a much lesser degree in rye and wheat, in amounts of about 7%, 5%, 2% and less than 1%, respectively), the cell wall of baker's yeast, certain types of fungi, and many kinds of mushrooms. The differences between soluble and insoluble beta-glucans are significant in regards to application, mode of action, and overall biological activity. A growing body of science indicates that beta-glucans promote health in a number of important ways. Beta-glucans have been studied for their hypocholesterolemic effects; these mechanisms include: reducing the intestinal absorption of cholesterol and bile acids by binding to glucans; shifting the liver from cholesterol syntheses to bile acid production; and fermentation by intestinal bacteria to short-chain fatty acids, which are absorbed and inhibit hepatic cholesterol syntheses. Several studies have also shown that oat beta-glucans blunt the glycemic and insulin response. Moreover, beta-1,3-glucans improve the body's immune system defense against foreign invaders by enhancing the ability of macrophages, neutrophils and natural killer cells to respond to and fight a wide range of challenges such as bacteria, viruses, fungi, and parasites. Finally, there is renewed interest in the potential usefulness of beta-glucan as a radioprotective drug for chemotherapy, radiation therapy and nuclear emergencies, particularly because glucan can be used not only as a treatment, but also as a prophylactic.

Topics: Animals; Bacterial Infections; beta-Glucans; Blood Glucose; Cholesterol, LDL; Humans; Hyperlipidemias; Immune System; Insulin; Mice; Neoplasms; Radiation Injuries, Experimental; Triglycerides

Postoperative infections remain common after high-risk gastrointestinal procedures. PGG-glucan (Betafectin; Alpha Beta Technology Inc, Worcester, Mass), derived from yeast cell walls, promotes phagocytosis and intracellular killing of bacterial pathogens by leukocytes, prevents infection in an animal model of wound infection, and acts synergistically with antibiotics to reduce mortality in rat peritonitis.. We hypothesized that infectious complications in these patients might be reduced by the administration of a nonspecific immune-enhancing agent.. Multicenter, prospective, randomized, double-blind, placebo-controlled trial of 1249 patients prospectively stratified into colorectal or noncolorectal strata.. Thirty-nine medical centers throughout the United States.. Aged 18 years or older, scheduled for gastrointestinal procedure lasting 2 to 8 hours, with 2 or more defined risk factors.. PGG-glucan, 0.5 mg/kg or 1.0 mg/kg, or placebo once preoperatively and 3 times postoperatively. All patients received standardized antibiotic prophylaxis.. Serious infection or death within 30 days.. All randomized patients revealed no difference in serious infections and deaths in the treated groups compared with placebo groups (15% vs 14%, P>.90). In the prospectively defined noncolorectal stratum (n = 391), PGG-glucan administration was associated with a statistically significant relative reduction (39%) in serious infections and death (placebo, 46 [36%] of 129 vs either PGG-glucan group, 29 [21%] of 132 and 28 [22%] of 130, P<.02). PGG-glucan reduced postoperative infection or death in malnourished patients having noncolorectal procedures (31 [44%] of 70, placebo group; 16 [24%] of 68, 0.5-mg/kg PGG-glucan group; 12 [17%] of 72, 1.0-mg/kg PGG-glucan group; P<.001). Study drug was stopped owing to adverse effects more frequently for patients receiving PGG-glucan than placebo (2%, 4%, and 7% for the placebo group, 0.5-mg/kg PGG-glucan group, and 1.0-mg/kg PGG-glucan group, respectively, P<.003).. Perioperative administration of PGG-glucan reduced serious postoperative infections or death by 39% after high-risk noncolorectal operations.

Topics: Adjuvants, Immunologic; Adult; Bacterial Infections; beta-Glucans; Digestive System Surgical Procedures; Glucans; Humans; Middle Aged; Postoperative Complications; Prospective Studies; Risk Factors

To examine the safety and efficacy of multiple doses of PGG-glucan (poly-[1-6]-B-D-glucopyranosyl-[1-3]-B-D-glucopyranose) in high-risk patients undergoing major thoracic or abdominal surgery.. An interventional, multicenter, double-blind, randomized, placebo-controlled study.. Four university-affiliated medical centers.. Sixty-seven high-risk patients undergoing major thoracic or abdominal surgery.. Patients were randomized in a 1:1:1:1 ratio to receive saline placebo or PGG-glucan at a dose of 0.1 mg/kg, 0.5 mg/kg, and 1.0 mg/kg or 2.0 mg/kg. One dose was administered before surgery and three doses were administered after surgery.. To examine the safety and efficacy of PGG-glucan infusion and to identify potentially important factors for a planned phase III study.. A dose-response trend with regard to infection incidence among patients who received PGG-glucan was observed. Serious infections occurred in four patients who received placebo and in three patients who received PGG-glucan at a dose of 0.1 mg/kg. However, only one patient who received PGG-glucan at a high dose had a serious infection. The incidence and severity of adverse events was comparable in all groups.. PGG-glucan was generally safe and well tolerated, may decrease postoperative infection rates, and warrants further investigation in a planned phase III trial.

Topics: Adjuvants, Immunologic; Adult; Aged; Bacterial Infections; beta-Glucans; Dose-Response Relationship, Drug; Double-Blind Method; Female; Glucans; Humans; Incidence; Male; Middle Aged; Postoperative Complications; Premedication

In a effect to prevent nosocomial pneumonia and sepsis, we treated patients with severe multiple trauma with an immunomodulator--beta 1-3 polyglucose (glucan). Forty-one patients with no infection at admission were stratified using Trauma Score and included in a randomized double-blind controlled trial. They were divided into a control group (n = 20) and a glucan group (n = 21). Pneumonia occurred in 11 of 20 patients in the control group and in two of 21 recipients of glucan (p < 0.01). Sepsis occurred in seven of 20 patients in the control group and in two of 21 patients treated with glucan (p < 0.05). Considering patients with pneumonia and sepsis, a decrease was observed in nosocomial infection from 65.0 to 14.4 percent (p < 0.001). The mortality rate related to infection was 30.0 percent in patients in the control group and 4.8 percent in the group treated with glucan (p < 0.05). The general mortality rate, cerebral deaths excluded, was 42.1 percent in the control group and 23.5 percent in the glucan group.

Topics: Adjuvants, Immunologic; Adult; Bacterial Infections; beta-Glucans; Craniocerebral Trauma; Cross Infection; Double-Blind Method; Female; Glucans; Humans; Incidence; Male; Multiple Trauma; Pneumonia

Many microbial pathogens produce a β-(1→6)-linked poly-

Topics: Animals; Antibodies, Bacterial; Antigens, Surface; Bacteria; Bacterial Infections; Bacterial Vaccines; beta-Glucans; Female; Immunization; Mice; Mice, Inbred BALB C; Transport Vesicles; Vaccines, Conjugate

β-glucan has been shown to increase non-specific immunity and resistance against infections or pathogenic bacteria in several fish species, but information regarding its trans-generational immune-enhancing effects is still rather limited. Lysozyme is a maternal immune factor playing an important role in the developing embryos of zebrafish. Here we clearly showe that β-glucan enhanced the level of C-type lysozyme in eggs of zebrafish, and the embryos derived from β-glucan-treated zebrafish were more resistant to bacterial challenge than control embryos. Moreover, the transferred lysozyme was apparently linked with the antimicrobial defense of early embryos. In addition, we also showed that β-glucan induced a significant increase in the synthesis of C-type lysozyme in previtellogenetic oocytes. Therefore, we show for the first time that β-glucan can enhance the lysozyme level in offspring via both inducing the transfer of the molecule from mothers to eggs and stimulating its endogenous production in oocytes.

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; beta-Glucans; Cells, Cultured; Diet; Eggs; Female; Fish Diseases; Gene Expression Regulation, Developmental; Immunity, Innate; Muramidase; Oocytes; Up-Regulation; Zebrafish; Zebrafish Proteins

Bacterial infections in cirrhotic patients with ascites are associated with a severe prognosis and an increased risk of death. The microbiological standard tests for the diagnosis of suspected infection, based on culture test of blood and ascitic fluid, are, in many cases (30-40 %), negative, even when patients show symptoms of infection. A multiple culture-independent protocol was applied and evaluated as a diagnostic and prognostic tool for the detection of bacterial infection in cirrhotic patients. Sixty-four culture-negative samples obtained from 34 cirrhotic patients, with PMN < 250 cells/μl of ascitic fluid, were screened for the presence of bacterial DNA, endotoxin, peptidoglycan/β-glucan and microscopically visible bacterial cells. Correlations between the presence of multiple markers and various clinical and laboratory parameters were evaluated. Bacterial DNA was detected in 23 samples collected from 16 patients; a large part of these samples also showed the presence of other bacterial markers, which was associated with a worsening of liver functionality, a higher incidence of infections during the follow-up and a higher mortality rate in our cohort of cirrhotic patients. We believe that the detection of additional bacterial markers in bacterial DNA-positive clinical samples makes the bacterial presence and its clinical significance more realistic and might be useful as early markers of an ongoing bacterial infection and in establishing a clinical prognosis.

Topics: Adult; Aged; Ascites; Ascitic Fluid; Bacteria; Bacterial Infections; beta-Glucans; Biomarkers; DNA, Bacterial; Endotoxins; Female; Humans; Liver Cirrhosis; Male; Middle Aged; Polymerase Chain Reaction; Prognosis; Severity of Illness Index

Clinical trials with biological modifiers targeting specific inflammatory mediators associated with severe sepsis have shown no or limited survival benefit. The approach taken in studies reported here was to limit the point source of intra-abdominal infection by potentiating innate immune function, thereby lessening the severity of sepsis and improving survival. Soluble beta-glucans, glucose polymers of the fungal cell wall, have been shown to stimulate innate immune host defense in animal and human studies when administered prior to an infectious challenge. We evaluated the effects of poly-(1,6)-β-d-glucopyranosyl-(1,3)-β-d-glucopyranose glucan (PGG glucan) on overall survival when administered intraperitoneally after the onset of polymicrobial infection by cecal ligation and puncture (CLP). Since gender-dependent differences in host immune response to infection have been reported, male and female mice were prospectively stratified for PGG glucan treatment. Outbred CD-1 mice were administered 10 mg/kg of body weight PGG glucan or the polysaccharide control, dextran, 1 h after CLP. Six hours after CLP, blood samples were obtained for cytokine measurements. Surprisingly, a gender-dependent effect on the response to PGG glucan was revealed. PGG glucan enhanced survival in female mice over a 10-day period, but survival in males was improved for only 24 h. In female mice, PGG glucan reduced interleukin-6 (IL-6) and IL-10 levels and reduced the bacterial burden in the liver. Ovariectomy abrogated the response to PGG glucan. Together, the translational potential of these findings is the indicated use of PGG glucan given locally, rather than intravenously, for improved source control during the management of sepsis. This therapy does not require prophylactic beta-glucan administration.

Topics: Animals; Bacterial Infections; Bacterial Load; beta-Glucans; Female; Immunologic Factors; Injections, Intraperitoneal; Interleukin-10; Interleukin-6; Liver; Male; Mice; Sepsis; Sex Factors; Survival Analysis; Time Factors

To evaluate the value of plasma 1, 3-β-D-glucan (G), serum mannan, galactomannan (GM) and cryptococcus capsular antigen assays for diagnosis of invasive fungal infections (IFI) in non-neutropenic adult patients.. This was a prospective case control study. Plasma and serum samples from 25 patients with IFI (candidiasis, aspergillosis, cryptococcosis, zygomycosis, pneumocystis carinii pneumonia), 27 patients with bacterial infections, and 25 healthy adults were collected from February 2007 to February 2009 in Beijing Hospital. The serum antigenic assays were performed and their sensitivity and specificity were analyzed. Optimal cut-off level of G test and mannan was established with receiver operating characteristic curve (ROC).. The concentration of G test in plasma of patients with IFI [89.4 (25.8, 336.9) ng/L] was significantly higher than that of patients with bacterial infection [8.1 (5.0, 34.9) ng/L, U = 120.5, P < 0.001] and healthy adults [3.8 (3.8, 26.0) ng/L, U = 76.5, P < 0.001]. The area under curve (AUC) was 0.858, and the optimal cut-off value was 71.7 ng/L. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 65.0% (13/20), 92.3% (48/52), 76.5% (13/17) and 87.2% (48/55) respectively. The concentration of mannan in serum from patients with candidiasis [1.13 (0.44, 1.22) µg/L] was significantly higher than that from patients with non-candidiasis IFI [0.21 (0.14, 0.27) µg/L, U = 19, P < 0.05], bacterial infection [0.26 (0.22, 0.32) µg/L, U = 36.5, P < 0.001] and healthy adults [0.25 (0.22, 0.30) µg/L, U = 29.5, P < 0.001]. The AUC was 0.894, and the optimal cut-off value was 0.41 µg/L. The sensitivity, specificity, PPV and NPV were 83.3% (10/12), 90.4% (47/52), 66.7% (10/15) and 96.0% (47/49) respectively. The sensitivity, specificity, PPV and NPV of GM antigen to diagnose aspergillosis were 25.0% (1/4), 96.1% (50/52), 33.3% (1/3) and 92.6% (50/54) respectively. The sensitivity, specificity, PPV and NPV of cryptococcus capsular antigen to diagnose cryptococcosis were all 100%.. 1,3-β-D-glucan, mannan and cryptococcus capsular antigen were useful for diagnosis of IFI in non-neutropenic adult patients. GM antigen did not show a good sensitivity for diagnosis of aspergillosis in non-neutropenic adult patients.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Fungal; Bacterial Infections; beta-Glucans; Case-Control Studies; Female; Galactose; Humans; Male; Mannans; Middle Aged; Mycoses; Predictive Value of Tests; Prospective Studies; Proteoglycans; Sensitivity and Specificity

Periodontal disease is the consequence of a mixed Gram-negative infection in the gingival sulcus and has been associated with deficits in the neutrophil response. A novel, and heretofore untested, alternative approach to therapy is the use of biological-response modulators that enhance the neutrophil response. Poly-beta1-6-glucotriosyl-beta1-3-glucopyranose glucan (PGG-glucan) is an immunomodulator, derived from yeast, which specifically enhances neutrophil priming, phagocytosis and bacterial killing while failing to induce inflammatory cytokine expression. The hypothesis tested was that PGG-glucan could enhance host resistance to a Gram-negative periodontal pathogen, Porphyromonas gingivalis. Chambers were implanted subcutaneously in the dorsolumbar region of C57BL/6J mice and allowed to heal for 14 days. PGG-glucan was administered subcutaneously to one-half of the animals and saline to the other half. In the first set of experiments the chambers were inoculated with P. gingivalis (A7436) at 4 x 10 (6), 4 x 10 (7), and 4 x 10 (8) colony-forming units (CFU). In the second set of experiments the chambers were inoculated with 5 x 10 (8) CFU of either P. gingivalis or Streptococcus sanguis, a Gram-positive oral microbe that is not periodontopathic. Chambers were sampled over the following 2 weeks. The results demonstrated that: (1). bacterial CFU and neutrophils increased with increasing bacterial inoculum (P<0.02); (2). bacterial CFU were lower in the PGG-glucan-treated animals than in the saline controls (P<0.02); and (3). neutrophil counts were higher in the PGG-glucan-treated animals than in the saline controls (P<0.01). These results indicate that PGG-glucan significantly enhances neutrophil emigration and bacterial killing, thus decreasing the bacterial infection in this model system.

Topics: Adjuvants, Immunologic; Analysis of Variance; Animals; Bacterial Infections; beta-Glucans; Cell Movement; Dose-Response Relationship, Drug; Female; Gingivitis; Glucans; Mice; Mice, Inbred C57BL; Models, Animal; Neutrophil Infiltration; Neutrophils; Porphyromonas gingivalis; Specific Pathogen-Free Organisms; Time Factors

Since beta-1,3-glucan is a common component of fungal cell wall, its detection might be useful in diagnosing invasive candidiasis. Not only endotoxin but beta-1,3-glucan activates proclotting enzyme contained in a conventional chromogenic limulus test (CCLT). Endotoxin activates this enzyme through factor C, while the beta-1,3-glucan activates through factor G. Since endotoxin specific test (EST) contains factor C, endotoxin would be quantified. By subtracting EST value from CCLT value, beta-1,3-glucan would be quantified. We named this value Fungal Index (FI), and examined if it actually reflects the candidal infection. Ninety-two patients were tested for CCLT and EST prospectively. FI increased significantly in candidal infection (p less than 0.05) but remained low in GNR infection. Moreover, FI increased proportionally to the severity of candidal infection. Elevated FI decreased when antifungal therapy was successful. Thus FI was a useful index not only in the diagnosis of invasive candidiasis but also in the evaluation of antifungal therapy.

Topics: Antifungal Agents; Bacterial Infections; beta-Glucans; Candidiasis; Chromogenic Compounds; Endotoxins; Escherichia coli; Glucans; Humans; Limulus Test; Mycology; Prospective Studies