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

Yang, William E

Suchindran, Sunil

Nicholson, Bradly P

McClain, Micah T

Burke, Thomas

Ginsburg, Geoffrey S

Harro, Clayton D

Chakraborty, Subhra

Sack, David A

Woods, Christopher W

Tsalik, Ephraim L

United States

2016-08-01T14:23:35Z

2016-05-01

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.

http://www.ncbi.nlm.nih.gov/pubmed/26787651

jiv593

1537-6613

https://hdl.handle.net/10161/12537

eng

Oxford University Press (OUP)

J Infect Dis

10.1093/infdis/jiv593

E. coli

bacterial infections

diarrheal illness

gene expression

immune response

microarrays

Adult

Enterotoxigenic Escherichia coli

Escherichia coli Infections

Female

Gene Expression Profiling

Host-Pathogen Interactions

Humans

Immunity, Innate

Male

Middle Aged

Oligonucleotide Array Sequence Analysis

RNA

Transcriptome

Young Adult

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

Journal article

Burke, Thomas|0000-0003-0592-5822

Ginsburg, Geoffrey S|0000-0003-4739-9808

Woods, Christopher W|0000-0001-7240-2453

Tsalik, Ephraim L|0000-0002-6417-2042

http://www.ncbi.nlm.nih.gov/pubmed/26787651

1495

1504

9

Biomedical Engineering

Clinical Science Departments

Duke

Duke Cancer Institute

Global Health Institute

Institutes and Centers

Institutes and Provost's Academic Units

Medicine

Medicine, Cardiology

Medicine, Infectious Diseases

Pathology

Pratt School of Engineering

School of Medicine

School of Nursing

School of Nursing - Secondary Group

University Institutes and Centers

Published

213