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J Clin Invest. 2018 Aug 1;128(8):3298-3311. doi: 10.1172/JCI97659. Epub 2018 Jun 25.

Enterotoxigenic Escherichia coli-blood group A interactions intensify diarrheal severity.

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Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri, USA.
Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Department of Medicine, Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Center for Cancer Research, Chemical Biology Laboratory, National Cancer Institute, Fredrick, Maryland, USA.
Department of Medicine, Division of Gastroenterology, Washington University School of Medicine, St. Louis, Missouri, USA.
Enteric Disease Department, Infectious Disease Directorate, Naval Medical Research Center, Silver Spring, Maryland, USA.
Molecular Microbiology and Microbial Pathogenesis Program, Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, Missouri, USA.
Medicine Service, Veterans Affairs Medical Center, St. Louis, Missouri, USA.


Enterotoxigenic Escherichia coli (ETEC) infections are highly prevalent in developing countries, where clinical presentations range from asymptomatic colonization to severe cholera-like illness. The molecular basis for these varied presentations, which may involve strain-specific virulence features as well as host factors, has not been elucidated. We demonstrate that, when challenged with ETEC strain H10407, originally isolated from a case of cholera-like illness, blood group A human volunteers developed severe diarrhea more frequently than individuals from other blood groups. Interestingly, a diverse population of ETEC strains, including H10407, secrete the EtpA adhesin molecule. As many bacterial adhesins also agglutinate red blood cells, we combined the use of glycan arrays, biolayer inferometry, and noncanonical amino acid labeling with hemagglutination studies to demonstrate that EtpA is a dominant ETEC blood group A-specific lectin/hemagglutinin. Importantly, we have also shown that EtpA interacts specifically with glycans expressed on intestinal epithelial cells from blood group A individuals and that EtpA-mediated bacterial-host interactions accelerate bacterial adhesion and effective delivery of both the heat-labile and heat-stable toxins of ETEC. Collectively, these data provide additional insight into the complex molecular basis of severe ETEC diarrheal illness that may inform rational design of vaccines to protect those at highest risk.


Bacterial infections; Bacterial vaccines; Glycobiology; Infectious disease; Vaccines

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