maltodextrin and Escherichia-coli-Infections

Trimethoprim is one of the most widely used antibiotics in the world. However, its efficacy is frequently limited by its poor water solubility and dose limiting toxicity. Prodrug strategies based on conjugation of oligosaccharides to trimethoprim have great potential for increasing the solubility of trimethoprim and lowering its toxicity, but they have been challenging to develop due to the sensitivity of trimethoprim to chemical modifications, and the rapid degradation of oligosaccharides in serum. In this report, we present a trimethoprim conjugate of maltodextrin termed TM-TMP, which increased the water solubility of trimethoprim by over 100 times, was stable to serum enzymes, and was active against urinary tract infections in mice. TM-TMP is composed of thiomaltose conjugated to trimethoprim, via a self-immolative disulfide linkage, and releases 4'-OH-trimethoprim (TMP-OH) after disulfide cleavage, which is a known metabolic product of trimethoprim and is as potent as trimethoprim. TM-TMP also contains a new maltodextrin targeting ligand composed of thiomaltose, which is stable to hydrolysis by serum amylases and therefore has the metabolic stability needed for in vivo use. TM-TMP has the potential to significantly improve the treatment of a wide number of infections given its high water solubility and the widespread use of trimethoprim.

Topics: Animals; Anti-Bacterial Agents; Escherichia coli; Escherichia coli Infections; Female; Maltose; Mice; Polysaccharides; Trimethoprim; Urinary Tract Infections

Crohn's disease (CD) is associated with intestinal dysbiosis evidenced by an altered microbiome forming thick biofilms on the epithelium. Additionally, adherent-invasive E. coli (AIEC) strains are frequently isolated from ileal lesions of CD patients indicating a potential role for these strains in disease pathogenesis. The composition and characteristics of the host microbiome are influenced by environmental factors, particularly diet. Polysaccharides added to food as emulsifiers, stabilizers or bulking agents have been linked to bacteria-associated intestinal disorders. The escalating consumption of polysaccharides in Western diets parallels an increased incidence of CD during the latter 20(th) century. In this study, the effect of a polysaccharide panel on adhesiveness of the CD-associated AIEC strain LF82 was analyzed to determine if these food additives promote disease-associated bacterial phenotypes. Maltodextrin (MDX), a polysaccharide derived from starch hydrolysis, markedly enhanced LF82 specific biofilm formation. Biofilm formation of multiple other E. coli strains was also promoted by MDX. MDX-induced E. coli biofilm formation was independent of polysaccharide chain length indicating a requirement for MDX metabolism. MDX exposure induced type I pili expression, which was required for MDX-enhanced biofilm formation. MDX also increased bacterial adhesion to human intestinal epithelial cell monolayers in a mechanism dependent on type 1 pili and independent of the cellular receptor CEACAM6, suggesting a novel mechanism of epithelial cell adhesion. Analysis of mucosa-associated bacteria from individuals with and without CD showed increased prevalence of malX, a gene essential for MDX metabolism, uniquely in the ileum of CD patients. These findings demonstrate that the ubiquitous dietary component MDX enhances E. coli adhesion and suggests a mechanism by which Western diets rich in specific polysaccharides may promote dysbiosis of gut microbes and contribute to disease susceptibility.

Topics: Animals; Antigens, CD; Bacterial Adhesion; Biofilms; Caco-2 Cells; Cell Adhesion; Cell Adhesion Molecules; Cell Line, Tumor; Crohn Disease; Diet; Disease Susceptibility; Epithelial Cells; Escherichia coli; Escherichia coli Infections; Fimbriae, Bacterial; Food Additives; GPI-Linked Proteins; HT29 Cells; Humans; Ileum; Intestinal Mucosa; Macrophages; Mice; Polysaccharides

Mutant screens and transcriptome studies led us to consider whether the metabolism of glucose polymers, i.e., maltose, maltodextrin, and glycogen, is important for Escherichia coli colonization of the intestine. By using the streptomycin-treated mouse model, we found that catabolism of the disaccharide maltose provides a competitive advantage in vivo to pathogenic E. coli O157:H7 and commensal E. coli K-12, whereas degradation of exogenous forms of the more complex glucose polymer, maltodextrin, does not. The endogenous glucose polymer, glycogen, appears to play an important role in colonization, since mutants that are unable to synthesize or degrade glycogen have significant colonization defects. In support of the hypothesis that E. coli relies on internal carbon stores to maintain colonization during periods of famine, we found that by providing a constant supply of a readily metabolized sugar, i.e., gluconate, in the animal's drinking water, the competitive disadvantage of E. coli glycogen metabolism mutants is rescued. The results suggest that glycogen storage may be widespread in enteric bacteria because it is necessary for maintaining rapid growth in the intestine, where there is intense competition for resources and occasional famine. An important implication of this study is that the sugars used by E. coli are present in limited quantities in the intestine, making endogenous carbon stores valuable. Thus, there may be merit to combating enteric infections by using probiotics or prebiotics to manipulate the intestinal microbiota in such a way as to limit the availability of sugars preferred by E. coli O157:H7 and perhaps other pathogens.

Topics: Animals; Drug Resistance, Bacterial; Escherichia coli Infections; Escherichia coli O157; Gluconates; Glycogen; Intestines; Male; Maltose; Mice; Mutation; Phenotype; Polysaccharides; Streptomycin; Time Factors

The influence of the administration of Lactobacillus plantarum, maltodextrin Maldex 150 and Raftifeed IPX fructooligosaccharides on the inhibition of adhesion of E. coli O8:K88 to the mucosa of the jejunum, ileum and colon as well as on the organic acid levels was investigated in 33 conventional piglets. The counts of E. coli K88 adhering to the jejunal mucosa were significantly decreased (p < 0.05) in Lact. plantarum + Maldex 150 and Lact. plantarum + Maldex 150 + Raftifeed IPX groups. The counts of E. coli K88 adhering to the colonic mucosa of Lact. plantarum + Maldex 150 + Raftifeed IPX and Lact. plantarum + Raftifeed IPX groups were significantly lower (p < 0.05) than in Lact. plantarum and Lact. plantarum + Maldex 150 animals. The acetic acid levels in the ileum and colon of the Lact. plantarum + Maldex 150 + Raftifeed IPX group and Lact. plantarum + Raftifeed IPX group were significantly higher (p < 0.05) than in the Lact. plantarum and Lact. plantarum + Maldex 150 group. The combination of Lact. plantarum, maltodextrin Maldex 150 and Raftifeed IPX proved to be the most effective one to inhibit the counts of E. coli O8:K88 adhering to the intestinal mucosa of the jejunum and colon of conventional piglets.

Topics: Acetic Acid; Animals; Animals, Suckling; Bacterial Adhesion; Chromatography, Thin Layer; Colony Count, Microbial; Dietary Carbohydrates; Escherichia coli; Escherichia coli Infections; Gastrointestinal Contents; Intestinal Mucosa; Lactic Acid; Lactobacillus plantarum; Oligosaccharides; Polysaccharides; Probiotics; Swine; Swine Diseases

The influence of preventive administration of Lactobacillus casei subsp. casei and maltodextrin KMS X-70 on Escherichia coli 08: K88 adhesion in the gastrointestinal tract of 11 conventional and 6 gnotobiotic piglets was investigated. The preventive administration of L. casei alone had almost no inhibitory effect on the adherence of E. coli to the jejunal mucosa of gnotobiotic and conventional piglets while the lactobacilli administered together with maltodextrin decreased the number of E. coli colonising jejunal mucosa of gnotobiotic piglets by 1 logarithm (4.95 log 10/cm2) in comparison with the control group (5.96 log 10/cm2). L. casei administered in combination with maltodextrin decreased the number of E. coli colonising the jejunum of conventional piglets by more than two and half logarithm (4.75 log 10/cm2, p < 0.05) in comparison with the control (7.42 log 10/cm2). The inhibitory effect of Lactobacillus casei and maltodextrin KMS X-70 on the adhesion of E. coli to the intestinal mucosa of conventional and gnotobiotic pigs was probably mediated by Lactobacillus--produced antibacterial substances and stimulation of immunity.

Topics: Animals; Bacterial Adhesion; Colon; Diarrhea; Escherichia coli; Escherichia coli Infections; Germ-Free Life; Ileum; Intestinal Mucosa; Jejunum; Lactic Acid; Lacticaseibacillus casei; Polysaccharides; Swine