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Am J Trop Med Hyg. 2016 Aug 3;95(2):440-3. doi: 10.4269/ajtmh.16-0161. Epub 2016 May 9.

Blood Group O-Dependent Cellular Responses to Cholera Toxin: Parallel Clinical and Epidemiological Links to Severe Cholera.

Author information

1
Division of Infectious Diseases, Department of Internal Medicine, Washington University School of Medicine, Saint Louis, Missouri.
2
Division of Gastroenterology, Department of Internal Medicine, Washington University School of Medicine, Saint Louis, Missouri.
3
Division of Gastroenterology, Department of Internal Medicine, Washington University School of Medicine, Saint Louis, Missouri. Molecular Microbiology and Microbial Pathogenesis Program, Division of Biology and Biomedical Sciences, Washington University School of Medicine, Saint Louis, Missouri.
4
Division of Infectious Diseases, Department of Internal Medicine, Washington University School of Medicine, Saint Louis, Missouri. Molecular Microbiology and Microbial Pathogenesis Program, Division of Biology and Biomedical Sciences, Washington University School of Medicine, Saint Louis, Missouri. Veterans Affairs Medical Center, Saint Louis, Missouri. jflecken@wustl.edu.

Abstract

Because O blood group has been associated with more severe cholera infections, it has been hypothesized that cholera toxin (CT) may bind non-O blood group antigens of the intestinal mucosae, thereby preventing efficient interaction with target GM1 gangliosides required for uptake of the toxin and activation of cyclic adenosine monophosphate (cAMP) signaling in target epithelia. Herein, we show that after exposure to CT, human enteroids expressing O blood group exhibited marked increase in cAMP relative to cells derived from blood group A individuals. Likewise, using CRISPR/Cas9 engineering, a functional group O line (HT-29-A(-/-)) was generated from a parent group A HT-29 line. CT stimulated robust cAMP responses in HT-29-A(-/-) cells relative to HT-29 cells. These findings provide a direct molecular link between blood group O expression and differential cellular responses to CT, recapitulating clinical and epidemiologic observations.

PMID:
27162272
PMCID:
PMC4973196
DOI:
10.4269/ajtmh.16-0161
[Indexed for MEDLINE]
Free PMC Article

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