Oral administration of formaldehyde-killed recombinant bacteria expressing a mimic of the Shiga toxin receptor protects mice from fatal challenge with Shiga-toxigenic Escherichia coli.
Gastrointestinal disease caused by Shiga toxin-producing Escherichia coli (STEC) is frequently complicated by life-threatening toxin-induced systemic sequelae, including the hemolytic uremic syndrome. We previously constructed a recombinant bacterium displaying a Shiga toxin receptor mimic on its surface which neutralized Shiga toxins with very high efficiency. Moreover, oral administration of the live bacterium completely protected mice from challenge with virulent STEC. In this study, we investigated the protective capacity of formaldehyde-killed receptor mimic bacteria, as these are likely to be safer for administration to humans. The killed bacteria completely protected STEC-challenged mice when administered three times daily; incomplete protection was achieved using two doses per day. Commencement of therapy could be delayed for up to 48 h after challenge without diminishing protection, depending on the virulence of the challenge strain. Thus, administration of this agent early in the course of human STEC disease may prevent progression to life-threatening complications.
Paton
J C
JC
Molecular Microbiology Unit, Women's and Children's Hospital, North Adelaide, South Australia 5006.
Rogers
T J
TJ
Morona
R
R
Paton
A W
AW
D000284:Administration, Oral; D000818:Animals; D004926:Escherichia coli / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000150:complications / Q000517:prevention & control*; D022361:Escherichia coli Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D005557:Formaldehyde; D006463:Hemolytic-Uremic Syndrome / Q000517:prevention & control; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018716:Molecular Mimicry; D011956:Receptors, Cell Surface / Q000276:immunology / Q000627:therapeutic use*; D022621:Shiga Toxin / Q000096:biosynthesis*; D014281:Trihexosylceramides / Q000276:immunology / Q000627:therapeutic use*; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000627:therapeutic use; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000627:therapeutic use
D022361:Escherichia coli Vaccines; D011956:Receptors, Cell Surface; D014281:Trihexosylceramides; D015164:Vaccines, Inactivated; D014614:Vaccines, Synthetic; D005557:Formaldehyde; C018549:globotriaosylceramide; D022621:Shiga Toxin