Infectious Diseases: Diarrheagenic E. coli/HUS

E. coli O157 and related bacteria are responsible for 100,000 infections in the US annually. People contract the bacteria by eating undercooked meat or by drinking contaminated liquids like milk. While infection can cause bloody diarrhea in adults, in 5-15% of children and the elderly it can lead to kidney disease and kidney failure, a condition known as hemolytic uremic syndrome (HUS). This syndrome is the single most important cause of acute kidney failure in children in the US and other developed countries. HUS can lead to death in some cases, and surviving patients often sustain serious kidney damage requiring dialysis or kidney transplantation. The Department of Infectious Disease and Global Health has recently developed a human monoclonal antibody therapy for HUS that we expect to test for efficacy in human clinical trials. We are also advancing development of recombinant antibody therapies for prevention of HUS. This antibody technology is described in more detail on the Recombinant Antibodies page.

Publications

  • Sheoran A, Jeong KI, Mukherjee J, Wiffin A, Singh P, Tzipori S. 2012. Biodistribution and elimination kinetics of systemic Stx2 by the Stx2A and Stx2B subunit-specific human monoclonal antibodies in mice. BMC Immunol. 13:27. PMID: 22655967
  • Pieper R, Zhang Q, Clark DJ, Huang ST, Suh MJ, Braisted JC, Payne SH, Fleischmann RD, Peterson SN, Tzipori S. 2011. Characterizing the Escherichia coli O157:H7 proteome including protein associations with higher order assemblies. PLoS One. 6:e26554. PMID: 22087229
  • Jeong KI, Chapman-Bonofiglio S, Singh P, Lee J, Tzipori S, Sheoran AS. 2010. In vitro and in vivo protective efficacies of antibodies that neutralize the RNA N-glycosidase activity of Shiga toxin 2. BMC Immunol. 11:16. PMID: 20334660
  • Jeong KI, Tzipori S, Sheoran AS. 2010. Shiga toxin 2-specific but not shiga toxin 1-specific human monoclonal antibody protects piglets challenged with enterohemorrhagic Escherichia coli producing shiga toxin 1 and shiga toxin 2. J Infect Dis. 201:1081-3. PMID: 20196656
  • Jeong KI, Zhang Q, Nunnari J, Tzipori S. 2010. A piglet model of acute gastroenteritis induced by Shigella dysenteriae Type 1. J Infect Dis. 201:903-11. PMID:20136414
  • Akiyoshi DE, Sheoran AS, Rich CM, Richard L, Chapman-Bonofiglio S, Tzipori S. 2010. Evaluation of Fab and F(ab')2 fragments and isotype variants of a recombinant human monoclonal antibody against Shiga toxin 2. Infect Immun. 78:1376-82. PMID:20086088
  • Zhang Q, Donohue-Rolfe A, Krautz-Peterson G, Sevo M, Parry N, Abeijon C, Tzipori S. 2009. Gnotobiotic piglet infection model for evaluating the safe use of antibiotics against Escherichia coli O157:H7 infection. J Infect Dis. 199:486-93. PMID:19125676
  • Krautz-Peterson G, Chapman-Bonofiglio S, Boisvert K, Feng H, Herman IM, Tzipori S, Sheoran AS. 2008. Intracellular neutralization of shiga toxin 2 by an a subunit-specific human monoclonal antibody. Infect Immun. 76:1931-9. PMID:18285498
  • Sheoran AS, Chapman-Bonofiglio S, Harvey BR, Mukherjee J, Georgiou G, Donohue-Rolfe A, Tzipori S. 2005. Human antibody against shiga toxin 2 administered to piglets after the onset of diarrhea due to Escherichia coli O157:H7 prevents fatal systemic complications. Infect Immun. 73:4607-13. PMID:16040972
  • Akiyoshi DE, Rich CM, O'Sullivan-Murphy S, Richard L, Dilo J, Donohue-Rolfe A, Sheoran AS, Chapman-Bonofiglio S, Tzipori S. 2005. Characterization of a human monoclonal antibody against Shiga toxin 2 expressed in Chinese hamster ovary cells. Infect Immun. 73:4054-61. PMID:15972493
  • Tzipori S, Sheoran A, Akiyoshi D, Donohue-Rolfe A, Trachtman H. 2004. Antibody therapy in the management of shiga toxin-induced hemolytic uremic syndrome. Clin Microbiol Rev. 17:926-41. PMID:15489355
  • Sheoran AS, Chapman S, Singh P, Donohue-Rolfe A, Tzipori S. 2003. Stx2-specific human monoclonal antibodies protect mice against lethal infection with Escherichia coli expressing Stx2 variants. Infect Immun. 71:3125-30. PMID:12761090
  • Mukherjee J, Chios K, Fishwild D, Hudson D, O'Donnell S, Rich SM, Donohue-Rolfe A, Tzipori S. 2002. Production and characterization of protective human antibodies against Shiga toxin 1. Infect Immun. 70:5896-9. PMID:12228326
  • Mukherjee J, Chios K, Fishwild D, Hudson D, O'Donnell S, Rich SM, Donohue-Rolfe A, Tzipori S. 2002. Human Stx2-specific monoclonal antibodies prevent systemic complications of Escherichia coli O157:H7 infection. Infect Immun. 70:612-9. PMID: 11796590
  • Donohue-Rolfe A, Kondova I, Oswald S, Hutto D, Tzipori S. 2000. Escherichia coli O157:H7 strains that express Shiga toxin (Stx) 2 alone are more neurotropic for gnotobiotic piglets than are isotypes producing only Stx1 or both Stx1 and Stx2. J Infect Dis. 181:1825-9. PMID:10823794
  • Donohue-Rolfe A, Kondova I, Mukherjee J, Chios K, Hutto D, Tzipori S. 1999. Antibody-based protection of gnotobiotic piglets infected with Escherichia coli O157:H7 against systemic complications associated with Shiga toxin 2. Infect Immun. 67(7):3645-8. PMID:10377152
  • Gunzer F, Bohn U, Fuchs S, Mühldorfer I, Hacker J, Tzipori S, Donohue-Rolfe A. 1998. Construction and characterization of an isogenic slt-ii deletion mutant of enterohemorrhagic Escherichia coli. Infect Immun. 66:2337-41. PMID:9573126
  • Tzipori S, Gunzer F, Donnenberg MS, de Montigny L, Kaper JB, Donohue-Rolfe A. 1995. The role of the eaeA gene in diarrhea and neurological complications in a gnotobiotic piglet model of enterohemorrhagic Escherichia coli infection. Infect Immun. 63:3621-7. PMID:7642299