High-molecular-weight polyethylene glycol prevents lethal sepsis due to intestinal Pseudomonas aeruginosa.
OBJECTIVE
During stress, erosion of protective intestinal mucus occurs in association with adherence to and disruption of the intestinal epithelial barrier by invading opportunistic microbial pathogens. The aims of this study were to test the ability of a high-molecular-weight polyethylene glycol compound, polyethylene glycol 15-20, to protect the intestinal epithelium against microbial invasion during stress.


METHODS
The ability of polyethylene glycol 15-20 to protect the intestinal epithelium against the opportunistic pathogen Pseudomonas aeruginosa was tested in cultured Caco-2 cells. Bacterial virulence gene expression, bacterial adherence, and transepithelial electrical resistance were examined in response to apical inoculation of P. aeruginosa onto Caco-2 cells. Complementary in vivo studies were performed in a murine model of lethal sepsis due to intestinal P. aeruginosa in which surgical stress (30% hepatectomy) was combined with direct inoculation of P. aeruginosa into the cecum.


RESULTS
High-molecular-weight polyethylene glycol (polyethylene glycol 15-20) conferred complete protection against the barrier-dysregulating effects of P. aeruginosa in Caco-2 cells. Intestinal application of polyethylene glycol 15-20 in stressed mice protected against the lethal effects of intestinal P. aeruginosa. Mechanisms of this effect seem to involve the ability of polyethylene glycol 15-20 to distance P. aeruginosa from the intestinal epithelium and render it completely insensate to key environmental stimuli that activate its virulence.


CONCLUSIONS
High-molecular-weight polyethylene glycol has the potential to function as a surrogate mucin within the intestinal tract of a stressed host by inhibiting key interactive events between colonizing microbes and their epithelial cell targets.
Wu
Licheng
L
Department of Surgery, University of Chicago, IL 60637, USA.
Zaborina
Olga
O
Zaborin
Alex
A
Chang
Eugene B
EB
Musch
Mark
M
Holbrook
Christopher
C
Shapiro
James
J
Turner
Jerrold R
JR
Wu
Guohui
G
Lee
Ka Yee C
KY
Alverdy
John C
JC
D000818:Animals; D018938:Caco-2 Cells; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000382:microbiology; D007422:Intestines / Q000187:drug effects / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology*; D011552:Pseudomonas Infections / Q000401:mortality* / Q000517:prevention & control*; D011550:Pseudomonas aeruginosa; D013501:Surface-Active Agents / Q000737:chemistry / Q000494:pharmacology*
D013501:Surface-Active Agents; D011092:Polyethylene Glycols