Transcriptomic Analysis of the Host Response and Innate Resilience to Enterotoxigenic Escherichia coli Infection in Humans.
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 articleSubject
E. colibacterial 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
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https://hdl.handle.net/10161/12537Published Version (Please cite this version)
10.1093/infdis/jiv593Publication 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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Show full item recordScholars@Duke
Thomas Burke
Manager, Systems Project
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.
Micah Thomas McClain
Associate Professor of Medicine
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
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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