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

The Journal of Clinical Investigation
Pardeep KumarJames Fleckenstein

Abstract

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 an...Continue Reading

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Citations

Aug 22, 2018·Infection and Immunity·Yuehui ZhuJames M Fleckenstein
Mar 5, 2019·Current Infectious Disease Reports·James M Fleckenstein, F Matthew Kuhlmann
Nov 23, 2019·PLoS Neglected Tropical Diseases·F Matthew KuhlmannJames M Fleckenstein
Oct 20, 2020·American Journal of Physiology. Gastrointestinal and Liver Physiology·Jianyi YinMark Donowitz
Nov 4, 2020·Proceedings of the National Academy of Sciences of the United States of America·Alaullah SheikhJames M Fleckenstein
Jan 29, 2021·Stem Cells International·Viktoria HentschelMartin Müller
May 25, 2021·Gastroenterology Clinics of North America·James M FleckensteinAlaullah Sheikh
Jul 3, 2021·Microorganisms·Richard WalkerLouis Bourgeois
Jul 19, 2021·Trends in Microbiology·Sohyoung LeeJeongmin Song
Jul 18, 2021·The Journal of Infectious Diseases·James M Fleckenstein, Alaullah Sheikh

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Datasets Mentioned

BETA
D82843.2

Methods Mentioned

BETA
glycosylation
biolayer interferometry
pull-down
FACS
scraping
biosensors
biopsy
PCR
genotyping
flow cytometry

Clinical Trials Mentioned

NCT01739231
NCT01060748
NCT00844493
NCT01922856

Software Mentioned

gplots
RColorBrewer
Octet
Volocity 3D
R
GenePix Pro
Image J
Fiji
FlowJo

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