A whole-genome RNAi screen uncovers a novel role for human potassium channels in cell killing by the parasite Entamoeba histolytica

Scientific Reports
Chelsea MarieW A Petri

Abstract

The parasite Entamoeba histolytica kills human cells resulting in ulceration, inflammation and invasion of the colonic epithelium. We used the cytotoxic properties of ameba to select a genome-wide RNAi library to reveal novel host factors that control susceptibility to amebic killing. We identified 281 candidate susceptibility genes and bioinformatics analyses revealed that ion transporters were significantly enriched among susceptibility genes. Potassium (K(+)) channels were the most common transporter identified. Their importance was further supported by colon biopsy of humans with amebiasis that demonstrated suppressed K(+) channel expression. Inhibition of human K(+) channels by genetic silencing, pharmacologic inhibitors and with excess K(+) protected diverse cell types from E. histolytica-induced death. Contact with E. histolytica parasites triggered K(+) channel activation and K(+) efflux by intestinal epithelial cells, which preceded cell killing. Specific inhibition of Ca(2+)-dependent K(+) channels was highly effective in preventing amebic cytotoxicity in intestinal epithelial cells and macrophages. Blockade of K(+) efflux also inhibited caspase-1 activation, IL-1β secretion and pyroptotic death in THP-1 macrophages. ...Continue Reading

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Citations

Dec 4, 2015·PLoS Neglected Tropical Diseases·Joyobrato NathJaishree Paul
Dec 8, 2017·Parasitology·Elisabeth LabruyèreNancy Guillén
Jun 4, 2020·Physiology·Eileen Uribe-Querol, Carlos Rosales
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Methods Mentioned

BETA
biopsies
IECs
gene knockdown
transfection
PMA
biopsy
ELISA

Software Mentioned

GraphPad Prism
DAVID Bioinformatics resource
DAVID
GA

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