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Type: Journal article
Title: Protection against Shiga-toxigenic Escherichia coli by non-genetically modified organism receptor mimic bacterial ghosts
Author: Paton, A.
Chen, A.
Wang, H.
McAllister, L.
Höggerl, F.
Mayr, U.
Shewell, L.
Jennings, M.
Morona, R.
Lubitz, W.
Paton, J.
Citation: Infection and Immunity, 2015; 83(9):3526-3533
Publisher: American Society for Microbiology
Issue Date: 2015
ISSN: 0019-9567
Statement of
Adrienne W. Paton, Austen Y. Chen, Hui Wang, Lauren J. McAllister, Florian Höggerl, Ulrike Beate Mayr, Lucy K. Shewell, Michael P. Jennings, Renato Morona, Werner Lubitz, James C. Paton
Abstract: Shiga-toxigenic Escherichia coli (STEC) causes severe gastrointestinal infections in humans that may lead to life-threatening systemic sequelae, such as the hemolytic uremic syndrome (HUS). Rapid diagnosis of STEC infection early in the course of disease opens a window of opportunity for therapeutic intervention, for example, by administration of agents that neutralize Shiga toxin (Stx) in the gut lumen. We previously developed a recombinant bacterium that expresses a mimic of the Stx receptor globotriaosyl ceramide (Gb3) on its surface through modification of the lipopolysaccharide (A. W. Paton, R. Morona, and J. C. Paton, Nat Med 6:265-270, 2000, This construct was highly efficacious in vivo, protecting mice from otherwise fatal STEC disease, but the fact that it is a genetically modified organism (GMO) has been a barrier to clinical development. In the present study, we have overcome this issue by development of Gb3 receptor mimic bacterial ghosts (BGs) that are not classified as GMOs. Gb3-BGs neutralized Stx1 and Stx2 in vitro with high efficiency, whereas alternative Gb3-expressing non-GMO subbacterial particles (minicells and outer membrane blebs) were ineffective. Gb3-BGs were highly efficacious in a murine model of STEC disease. All mice (10/10) treated with Gb3-BGs survived challenge with a highly virulent O113:H21 STEC strain and showed no pathological signs of renal injury. In contrast, 6/10 mice treated with control BGs succumbed to STEC challenge, and survivors exhibited significant weight loss, neutrophilia, and histopathological evidence of renal damage. Thus, Gb3-BGs offer a non-GMO approach to treatment of STEC infection in humans, particularly in an outbreak setting.
Keywords: Shiga-Toxigenic Escherichia coli
Rights: Copyright © 2015, American Society for Microbiology. All Rights Reserved.
RMID: 0030031184
DOI: 10.1128/IAI.00669-15
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Appears in Collections:Molecular and Biomedical Science publications

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