Citrobacter rodentium Infection Alters Murine Colonic microRNA Signature

Abstract

MicroRNAs (miRs) have been suggested to play a part in the interaction between pathogenic bacteria and host cells. Citrobacter rodentium is a murine pathogen causing transmissible colonic hyperplasia and colitis with similar pathogenicity as the foodborne enterohaemorrhagic Escherichia coli O157:H7 in humans. This study aimed to examine if colonic microRNA signature is altered during C. rodentium infection. C57Bl6/J male mice were randomized to C. rodentium‐infected or control group, and sacrificed at the peak of infection (10 days post‐infection). Crypt hyperplasia and intestinal inflammation were confirmed by histology and in vivo permeability test. Colonic RNA was used to profile 578 miRs by NanoString technology. Statistics and hierarchical clustering were performed in R. Gene targets of the differentially expressed miRs were identified in silico by prediction algorithms and cross‐matching with experimentally verified targets databases. Ninety‐four miRs were differentially expressed (p<0.05), with 42 downregulated and 52 upregulated vs control (0.2‐8.6 fold), and infected samples clustered together and separately from the controls based on their expression profile. Many of these miRs, including miR‐21, miR‐148a, and miR‐152, are known to regulate barrier function, cell proliferation and inflammatory pathways. Moreover, prediction analysis revealed that globally gene targets are mainly involved in cell cycle and immune response. This study shows that C. rodentium infection alters the colonic microRNA signature; differentially expressed miRs may be involved in the pathogenicity mechanism and serve as targets of nutritional or therapeutic interventions.Funding: NSERC, JP Bickell Foundation, and NSERC Alexander Graham Bell Canada Graduate Scholarship