Defence and adaptation mechanisms of the intestinal epithelium upon infection.

The intestinal epithelium is a monolayer of polarized columnar cells that act as a border between the host and its environment and are the first line of defence against the luminal microbes. In addition to providing a physical barrier, the epithelium possesses a multitude of active mechanisms to fight invading pathogens and regulate the composition and spatial distribution of commensals. The different epithelial cell types have unique functions in this context, and crosstalk with the immune system further modulates their intricate antimicrobial responses.

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

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.

Genotoxic Effect of Paratyphi A Infection on Human Primary Gallbladder Cells.

Carcinoma of the gallbladder (GBC) is the most frequent tumor of the biliary tract. Despite epidemiological studies showing a correlation between chronic infection with Typhi/Paratyphi A and GBC, the underlying molecular mechanisms of this fatal connection are still uncertain. The murine serovar Typhimurium has been shown to promote transformation of genetically predisposed cells by driving mitogenic signaling.

Colibactin DNA-damage signature indicates mutational impact in colorectal cancer.

The mucosal epithelium is a common target of damage by chronic bacterial infections and the accompanying toxins, and most cancers originate from this tissue. We investigated whether colibactin, a potent genotoxin associated with certain strains of Escherichia coli, creates a specific DNA-damage signature in infected human colorectal cells. Notably, the genomic contexts of colibactin-induced DNA double-strand breaks were enriched for an AT-rich hexameric sequence motif, associated with distinct DNA-shape characteristics.