Basic-alimentary tractHigh-molecular-weight polyethylene glycol prevents lethal sepsis due to intestinal Pseudomonas aeruginosa☆
Section snippets
Bacterial strains, epithelial cell lines, and polyethylene glycol solutions
P. aeruginosa strain 27853 (PA27853; American Type Culture Collection, Manassas, VA) is a nonmucoid clinical strain originally isolated from a blood culture. All experiments were performed with Caco-2/C2bbe, or C2, cells (passage 51–68) and were obtained as a generous gift of Dr. Mark Mooseker (Yale University, New Haven, CT). C2 cells are Caco-2 subclones that are highly differentiated intestinal epithelial cells.10 Two PEGs of different molecular weights were purchased from Sigma (St. Louis,
Results
PEG 15–20 protects against lethal gut-derived sepsis due to P. aeruginosa in mice after 30% hepatectomy. Direct cecal injection of PA27853 into mice who underwent a 30% surgical hepatectomy resulted in a state of clinical sepsis with no survivors at 48 hours (Figure 2A). Mice undergoing sham laparotomy without hepatectomy (controls), similarly injected with P. aeruginosa, survived completely without any clinical signs of sepsis (Figure 2A). To determine the ability of PEG solutions to prevent
Discussion
In this study, the ability of PEG 15–20 to protect the intestinal epithelium against an opportunistic colonizing pathogen was assessed. Specifically, the ability of PEG to inactivate the lethal effects of intestinal P. aeruginosa, one of the more common causes of fatal gut-derived sepsis in an immunocompromised host, was tested.19, 20, 21 Data from this show that there are striking effects of PEG 15–20 that parallel the function of intestinal mucus. Because intestinal mucus exerts its effects
Acknowledgements
The authors thank Dr. Klaus Winzer and Dr. Paul Williams, University of Nottingham, for helpful technical advice; Raphael Lee, M.D., Sc.D., director of the Center for Molecular Repair, University of Chicago, and William Cromie, M.D., for helpful conversations; and Shirley Bond, Cancer Center Digital Light Microscopy Facility at the University of Chicago, for technical assistance. The Escherichia coli/Pseudomonas aeruginosa shuttle vector pUCP24 was a gift of Dr. H. P. Schweizer, Colorado State
References (32)
- et al.
Reduction of colonic mucus by repeated short-term stress enhances experimental colitis in rats
J Physiol Paris
(2001) - et al.
Construction of improved Escherichia-Pseudomonas shuttle vectors derived from pUC18/19 and sequence of the region required for their replication in Pseudomonas aeruginosa
Gene
(1994) - et al.
Whole-gut lavage in children using an iso-osmolar solution containing polyethelene glycol (Golytely)
J Pediatr Surg
(1988) - et al.
Triggering the ExoS regulon of Pseudomonas aeruginosaa GFP-reporter analysis of exoenzyme (Exo) S, ExoT, and ExoU synthesis
Microb Pathog
(2000) - et al.
Infection rates in surgical neonates and infants receiving parenteral nutritiona five-year prospective study
J Hosp Infect
(2002) - et al.
Surface hydrophobicity of the rat colonic mucosa is a defensive barrier against macromolecules and toxins
Gut
(2000) - et al.
Surface hydrophobicity of the intestinal tract
Am J Physiol
(1992) - et al.
Lipopolysaccharide-induced gastrointestinal injury in ratsrole of surface hydrophobicity and bile salts
Shock
(2002) - et al.
Intestinal mucin inhibits adhesion of human enteropathogenic Escherichia coli to HEp-2 cells
J Pediatr Gastroenterol Nutr
(1995) - et al.
Interactions between Yersinia enterocolitica and rabbit ileal mucusgrowth, adhesion, penetration, and subsequent changes in surface hydrophobicity and ability to adhere to ileal brush border membrane vesicles
Infect Immun
(1991)
Measurements of attractive forces between proteins and end-grafted polyethylene glycol chains
Proc Natl Acad Sci U S A
The key role of Pseudomonas aeruginosa PA-I lectin on experimental gut-derived sepsis
Ann Surg
Gut-derived sepsis occurs when the right pathogen with the right virulence genes meets the right hostevidence for in vivo virulence expression in Pseudomonas aeruginosa
Ann Surg
Characterization of the enterocyte-like brush border cytoskeleton of the C2bbe clones of the human intestinal cell line, Caco-2
J Cell Sci
Increased type 1 fimbrial expression among commensal Escherichia coli isolates in the murine cecum following catabolic stress
Infect Immun
Microtubule targeting of substrate contacts promotes their relaxation and dissociation
J Cell Biol
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Supported by National Institutes of Health Grants RO1 GM62344-01 (to J.C.A.) and DK619131 (to J.R.T.), Digestive Diseases Research Core Center Grant DK 47722 (to E.B.C.), the David and Lucile Pachard Foundation Grant 99-1465 (to K.Y.C.L.), and the University of Chicago Materials Research Science and Engineering Centers Program of the National Science Foundation under Award DMR 9808595 (to K.Y.C.L.).
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L.W. and O.Z. contributed equally to this work.