Dataset Information

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.

SUBMITTER: Yang WE

PROVIDER: S-EPMC5007733 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Publications

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

Yang William E WE Suchindran Sunil S Nicholson Bradly P BP McClain Micah T MT Burke Thomas T Ginsburg Geoffrey S GS Harro Clayton D CD Chakraborty Subhra S Sack David A DA Woods Christopher W CW Tsalik Ephraim L EL

The Journal of infectious diseases 20160118 9

<h4>Background</h4>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.<h4>Methods</h4>We challenged 30 healthy adults with an unattenuated ETEC strain, and collected serial blood samples shortly after inoculation and daily for ...[more]

PMID: 26787651

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Project description:UnlabelledEnterotoxigenic E. coli (ETEC) can cause severe diarrhea and death in children in developing countries; however, bacterial diversity in natural infection is uncharacterized. In this study, we explored the natural population variation of ETEC from individuals with cholera-like diarrhea. Genomic sequencing and comparative analysis of multiple ETEC isolates from twelve cases of severe diarrhea demonstrated clonal populations in the majority of subjects (10/12). In contrast, a minority of individuals (2/12) yielded phylogenomically divergent ETEC isolates. Detailed examination revealed that isolates also differed in virulence factor content. These genomic data suggest that severe, cholera-like ETEC infections are largely caused by a clonal population of organisms within individual patients. Additionally, the isolation of similar clones from geographically and temporally dispersed cases with similar clinical presentations suggests that some isolates are particularly suited for virulence. The identification of multiple genomically diverse isolates with variable virulence factor profiles from a single subject highlights the dynamic nature of ETEC, as well as a potential weakness in the examination of cultures obtained from a single colony in clinical settings. These findings have implications for vaccine design and provide a framework for the study of population variation in other human pathogens.ImportanceEnterotoxigenic Escherichia coli (ETEC) has been identified as one of the major causes of diarrheal diseases in children as well as travelers. It has been previously appreciated that this pathogenic variant of E. coli is diverse, both at the genomic level, as defined with multilocus sequence typing, and with regard to the presence or absence of virulence factors within clonal groups. Using whole-genome sequencing and comparative analysis, we identified and characterized diverse enterotoxigenic E. coli isolates from individual patients. In 17% of patients, we identified multiple distinct ETEC isolates, each with unique genomic features and in some cases diverse virulence factor profiles. These studies ascertained that any one person may be colonized by multiple pathogenic ETEC isolates, which may impact how we think about the development of vaccines and therapeutics against these organisms.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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