Transcriptomic Analysis of the Host Response and Innate Resilience to Enterotoxigenic Escherichia coli Infection in Humans.

Published

Journal Article

BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) is a globally prevalent cause of diarrhea. Though usually self-limited, it can be severe and debilitating. Little is known about the host transcriptional response to infection. We report the first gene expression analysis of the human host response to experimental challenge with ETEC. METHODS: We challenged 30 healthy adults with an unattenuated ETEC strain, and collected serial blood samples shortly after inoculation and daily for 8 days. We performed gene expression analysis on whole peripheral blood RNA samples from subjects in whom severe symptoms developed (n = 6) and a subset of those who remained asymptomatic (n = 6) despite shedding. RESULTS: Compared with baseline, symptomatic subjects demonstrated significantly different expression of 406 genes highlighting increased immune response and decreased protein synthesis. Compared with asymptomatic subjects, symptomatic subjects differentially expressed 254 genes primarily associated with immune response. This comparison also revealed 29 genes differentially expressed between groups at baseline, suggesting innate resilience to infection. Drug repositioning analysis identified several drug classes with potential utility in augmenting immune response or mitigating symptoms. CONCLUSIONS: There are statistically significant and biologically plausible differences in host gene expression induced by ETEC infection. Differential baseline expression of some genes may indicate resilience to infection.

Full Text

Duke Authors

Cited Authors

  • Yang, WE; Suchindran, S; Nicholson, BP; McClain, MT; Burke, T; Ginsburg, GS; Harro, CD; Chakraborty, S; Sack, DA; Woods, CW; Tsalik, EL

Published Date

  • May 1, 2016

Published In

Volume / Issue

  • 213 / 9

Start / End Page

  • 1495 - 1504

PubMed ID

  • 26787651

Pubmed Central ID

  • 26787651

Electronic International Standard Serial Number (EISSN)

  • 1537-6613

Digital Object Identifier (DOI)

  • 10.1093/infdis/jiv593

Language

  • eng

Conference Location

  • United States