Abstract
Citrobacter rodentium is a murine pathogen causing transmissible colonic hyperplasia and colitis with a pathogenic mechanism similar to foodborne enterohaemorrhagic Escherichia coli in humans. Mechanisms underlying intestinal responses to C. rodentium infection are incompletely understood. We identified 24 colonic microRNAs (miRNAs) as significantly deregulated in response to C. rodentium, including miR-7a, -17, -19a, -20a, -20b, -92a, -106a, -132, -200a, and -2137; most of these miRNAs belong to the oncogenic miR-17-92 clusters. Pathways involved in cell cycle, cancers, and immune responses were enriched among the predicted targets of these miRNAs. We further demonstrated that an apoptosis facilitator, Bim, is a candidate gene target of miRNA-mediated host response to the infection. These findings suggest that host miRNAs participate in C. rodentium pathogenesis and may represent novel treatment targets.
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Acknowledgements
This work was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC #356124) and the J. P. Bickell Foundation. Computational analysis was supported in part by NSERC (#203475), Ontario Research Fund (GL2-01-030), Canada Foundation for Innovation (CFI #225404, #30865), Canada Research Chair Program (CRC #225404), Ontario Research Fund (RE-03-020), and IBM. Elena Comelli holds the Lawson Family Chair in Microbiome Nutrition Research at the University of Toronto. Bijun Wen was partially supported by NSERC Alexander Graham Bell Canada Graduate Scholarship. NanoString service was provided by the Princess Margaret Genomics Centre, Toronto, Canada (www.pmgenomics.ca). The authors would like to thank the Division of Comparative Medicine staff at University of Toronto for help with animal care.
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Wen, B., Tokar, T., Taibi, A. et al. Citrobacter rodentium alters the mouse colonic miRNome. Genes Immun 20, 207–213 (2019). https://doi.org/10.1038/s41435-018-0026-z
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DOI: https://doi.org/10.1038/s41435-018-0026-z
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