Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/100011
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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
1098-5522
Statement of
Responsibility: 
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, http://dx.doi.org/10.1038/73111). 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
Grant ID: http://purl.org/au-research/grants/nhmrc/565526
http://purl.org/au-research/grants/nhmrc/1002792
http://purl.org/au-research/grants/arc/DP120103178
Appears in Collections:Molecular and Biomedical Science publications

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