Campylobacter jejuni Cas9 modulates the transcriptome in Caco-2 intestinal epithelial cells

Chinmoy Saha*, Deborah Horst-Kreft, Inez Kross, Peter J. van der Spek, Rogier Louwen, Peter van Baarlen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Article number1193
Number of pages15
JournalGenes
Volume11
Issue number10
DOIs
Publication statusPublished - Oct 2020

Keywords

  • Caco-2
  • Campylobacter jejuni
  • Cas9
  • Cell death
  • NF-B
  • P53

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