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

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Date
2016-05-01
Authors
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
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(11 total)
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Abstract
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.
Type
Journal article
Subject
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
Permalink
https://hdl.handle.net/10161/12537
Published Version (Please cite this version)
10.1093/infdis/jiv593
Publication Info
Yang, William E; Suchindran, Sunil; Nicholson, Bradly P; McClain, Micah T; Burke, Thomas; Ginsburg, Geoffrey S; ... Tsalik, Ephraim L (2016). Transcriptomic Analysis of the Host Response and Innate Resilience to Enterotoxigenic Escherichia coli Infection in Humans. J Infect Dis, 213(9). pp. 1495-1504. 10.1093/infdis/jiv593. Retrieved from https://hdl.handle.net/10161/12537.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Burke

Thomas Burke

Manager, Systems Project
Ginsburg

Geoffrey Steven Ginsburg

Adjunct Professor in the Department of Medicine
Dr. Geoffrey S. Ginsburg's research interests are in the development of novel paradigms for developing and translating genomic information into medical practice and the integration of personalized medicine into health care.
McClain

Micah Thomas McClain

Associate Professor of Medicine
Tsalik

Ephraim Tsalik

Adjunct Associate Professor in the Department of Medicine
My research is focused on understanding the dynamic between host and pathogen so as to discover and develop host-response markers that can diagnose and predict health and disease.  This new and evolving approach to diagnosing illness has the potential to significantly impact individual as well as public health considering the rise of antibiotic resistance. With any potential infectious disease diagnosis, it is difficult, if not impossible, to determine at the time of presentation
Woods

Christopher Wildrick Woods

Professor of Medicine
1. Emerging Infections 2. Global Health 3. Epidemiology of infectious diseases 4. Clinical microbiology and diagnostics 5. Bioterrorism Preparedness 6. Surveillance for communicable diseases 7. Antimicrobial resistance
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