HIGH-MOLECULAR WEIGHT POLYETHYELENE GLYCOL MODULATES E. COLI INTERACTIONS WITH INTESTINAL EPITHELIUM

Abstract

zPolyethylene glycol (PEG) compounds may adhere to and alter the electrical charge on living surfaces, and there is emerging evidence that PEG may act as a surrogate mucin to protect the intestinal tract from invading bacteria. Because PEGs are inert and nontoxic, PEGs may be attractive therapeutic agents to protect the intestinal epithelium from bacterial invasion in the stressed patient. Mature cultures containing 106 Caco-2 or HT-29 enterocytes were preincubated 1 hr with increasing concentrations of high molecular weight PEG (15,000-20,000 MW), then incubated 1 hr with 108Escherichia coli. Bacterial internalization was measured using the gentamicin protection assay. PEG had no noticeable effect on enterocyte viability (trypan blue staining) or morphology (Wright Giemsa stains viewed by light microscopy). As noted in the figure, PEG pretreatment was associated with a dose dependent decrease in E. coli internalization by both Caco-2 and HT-29 enterocytes (*indicates a P < 0.01 decrease versus 0% PEG, ANOVA with Fisher's post hoc). To test the effect of PEG in vivo, mice were divided into two groups. One group received drinking water supplemented with 5% PEG for the duration of an experiment in which all mice received oral streptomycin and bacitracin for 3d, followed by oral inoculation with streptomycin-resistant E. coli, followed by sacrifice 48 hr later. PEG-treated mice had a modest but statistically significant (P < 0.01) decrease (3-fold) in E. coli cecal colonization (9.5 ± 0.1 versus 9.1 ± 0.1, avg ± SE log10 cecal E. coli/g, n = 8 mice/group). Thus, high molecular weight PEG may limit E. coli intestinal overgrowth in the antibiotic-treated host, and PEG may also more directly interfere with the interactions of E. coli with the intestinal epithelium.Figure