Polyethylene glycol diminishes pathological effects of Citrobacter rodentium infection by blocking bacterial attachment to the colonic epithelia

Abstract

Infections from enteric bacteria such as enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic Escherichia coli (EHEC) are a public health threat worldwide. EPEC and EHEC are extracellular pathogens, and their interaction with host surface receptors is critical to the infection process. We previously demonstrated that polyethylene glycol (PEG) downregulates surface receptors in intestinal cells. Here we show that PEG decreases β1-integrin, the surface receptor in intestinal cells that is critical for EPEC and EHEC attachment. We hypothesized that PEG would inhibit the attachment of these enteric pathogens to host cells and improve clinical signs of infection. We found that attachment of the mouse enteric pathogen Citrobacter rodentium, which belongs to the same group of pathogens as EPEC and EHEC, was attenuated by the concurrent presence of PEG. Pretreatment with PEG, without concurrent presence during infection, also reduced bacterial attachment. This finding was further supported in vivo such as that PEG administered by gavage daily during infection as well as prior to infection significantly decreased C. rodentium in the colon and improved the appearance of the infected colon in mice. In addition, PEG decreased the β1-integrin in colonic mucosa and reduced the C. rodentium-induced activation of epidermal growth factor receptors. PEG also significantly reduced infection-induced colonic inflammation. Finally, PEG efficiently reduced C. rodentium shedding from the colon during infection. In conclusion, PEG can be an efficient and safe preventive agent against EPEC and EHEC infections.