Dataset Information

Campylobacter jejuni Cas9 Modulates the Transcriptome in Caco-2 Intestinal Epithelial Cells.

ABSTRACT: The zoonotic human pathogen Campylobacter jejuni is known for its ability to induce DNA-damage and cell death pathology in humans. The molecular mechanism behind this phenomenon involves nuclear translocation by Cas9, a nuclease in C. jejuni (CjeCas9) that is the molecular marker of the Type II CRISPR-Cas system. However, it is unknown via which cellular pathways CjeCas9 drives human intestinal epithelial cells into cell death. Here, we show that CjeCas9 released by C. jejuni during the infection of Caco-2 human intestinal epithelial cells directly modulates Caco-2 transcriptomes during the first four hours of infection. Specifically, our results reveal that CjeCas9 activates DNA damage (p53, ATM (Ataxia Telangiectasia Mutated Protein)), pro-inflammatory (NF-?B (Nuclear factor-?B)) signaling and cell death pathways, driving Caco-2 cells infected by wild-type C. jejuni, but not when infected by a cas9 deletion mutant, towards programmed cell death. This work corroborates our previous finding that CjeCas9 is cytotoxic and highlights on a RNA level the basal cellular pathways that are modulated.

SUBMITTER: Saha C

PROVIDER: S-EPMC7650535 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Campylobacter jejuni Cas9 Modulates the Transcriptome in Caco-2 Intestinal Epithelial Cells.

Saha Chinmoy C Horst-Kreft Deborah D Kross Inez I van der Spek Peter J PJ Louwen Rogier R van Baarlen Peter P

Genes 20201014 10

The zoonotic human pathogen Campylobacter jejuni is known for its ability to induce DNA-damage and cell death pathology in humans. The molecular mechanism behind this phenomenon involves nuclear translocation by Cas9, a nuclease in C. jejuni (CjeCas9) that is the molecular marker of the Type II CRISPR-Cas system. However, it is unknown via which cellular pathways CjeCas9 drives human intestinal epithelial cells into cell death. Here, we show that CjeCas9 released by C. je ...[more]

PMID: 33066557

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Project description:Campylobacter jejuni is a leading cause of bacterial foodborne illness in humans worldwide. However, C. jejuni naturally colonizes poultry without causing pathology where it resides deep within mucus of the cecal crypts. Mucus may modulate the pathogenicity of C. jejuni in a species-specific manner, where it is pathogenic in humans and asymptomatic in poultry. Little is known about how intestinal mucus from different host species affects C. jejuni gene expression. In this study we characterized the growth and transcriptome of C. jejuni NCTC11168 cultured in defined media supplemented with or without mucus isolated from avian (chicken or turkey) or mammalian (cow, pig, or sheep) sources. C. jejuni showed substantially improved growth over defined media, with mucus from all species, showing that intestinal mucus was an energy source for C. jejuni. Seventy-three genes were differentially expressed when C. jejuni was cultured in avian vs. mammalian mucus. Genes associated with iron acquisition and resistance to oxidative stress were significantly increased in avian mucus. Many of the differentially expressed genes were flanked by differentially expressed antisense RNA asRNA, suggesting a role in gene regulation. This study highlights the interactions between C. jejuni and host mucus and the impact on gene expression, growth and invasion of host cells, suggesting important responses to environmental cues that facilitate intestinal colonization. IMPORTANCE Campylobacter jejuni infection of humans is an important health problem world-wide and is the leading bacterial cause of foodborne illnesses in U.S. The main route for exposure for humans is consumption of poultry meat contaminated during processing. C. jejuni is frequently found in poultry, residing within the mucus of the intestinal tract without causing disease. It is not clear why C. jejuni causes disease in some animals and humans, while leaving birds without symptoms. To understand its activity in birds, we characterized C. jejuni responses to poultry mucus to identify genes turned on in the intestinal tract of birds. We identified genes important for colonization and persistence within the poultry gut, turned on when C. jejuni was exposed to poultry mucus. Our findings are an important step in understanding how C. jejuni responds and interacts in the poultry gut, and may identify ways to reduce C. jejuni in birds.

Dataset Information

Campylobacter jejuni Cas9 Modulates the Transcriptome in Caco-2 Intestinal Epithelial Cells.

Publications

<i>Campylobacter jejuni</i> Cas9 Modulates the Transcriptome in Caco-2 Intestinal Epithelial Cells.

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