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Campylobacter jejuni promotes colorectal tumorigenesis through the action of cytolethal distending toxin.

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PubMed ID: 30377189

Imagen Publicación

He Z, Gharaibeh RZ, Newsome RC, Pope JL, Dougherty MW, Tomkovich S, Pons B, Mirey G, Vignard J, Hendrixson DR, Jobin C

Gut. 02 2019. doi: 10.1136/gutjnl-2018-317200

COMMENT: The study reveals the effect of Campylobacter jejuni on the development of colorectal cancer in mouse models

OBJECTIVE

Campylobacter jejuni produces a genotoxin, cytolethal distending toxin (cDt), which has Dnase activity and causes Dna double-strand breaks. although C. jejuni infection has been shown to promote intestinal inflammation, the impact of this bacterium on carcinogenesis has never been examined.

MAIN RESULTS

GF (germ free) ApcMin/+mice colonised with human clinical isolate C. jejuni 81–176 developed significantly more and larger tumours when compared with uninfected mice. C. jejuni with a mutated cdtB subunit, mutcdtB, attenuated C. jejuni-induced tumorigenesis in vivo and decreased Dna damage response in cells and enteroids. C. jejuni infection induced expression of hundreds of colonic genes, with 22 genes dependent on the presence of cdtB. the C. jejuni-infected group had a significantly different microbial gene expression profile compared with the mutcdtB group as shown by metatranscriptomic data, and different microbial communities as measured by 16S rDna sequencing. Finally, rapamycin could diminish the tumorigenic capability of C. jejuni.

CONCLUSIONS

Human clinical isolate C. jejuni 81–176 promotes colorectal cancer and induces changes in microbial composition and transcriptomic responses, a process dependent on CDT production.

Contributor

Marina Manrique