Genomic aberrations after short-term exposure to colibactin-producing E. coli transform primary colon epithelial cells.

ABSTRACT: Genotoxic colibactin-producing pks+ Escherichia coli induce DNA double-strand breaks, mutations, and promote tumor development in mouse models of colorectal cancer (CRC). Colibactin's distinct mutational signature is reflected in human CRC, suggesting a causal link. Here, we investigate its transformation potential using organoids from primary murine colon epithelial cells. Organoids recovered from short-term infection with pks+ E. coli show characteristics of CRC cells, e.g., enhanced proliferation, Wnt-independence, and impaired differentiation. Sequence analysis of Wnt-independent organoids reveals an enhanced mutational burden, including chromosomal aberrations typical of genomic instability. Although we do not find classic Wnt-signaling mutations, we identify several mutations in gene

SUBMITTER: Iftekhar A 

PROVIDER: S-EPMC7881031 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature