Microbiota and colorectal cancer: colibactin makes its mark

@article{Arthur2020MicrobiotaAC,
  title={Microbiota and colorectal cancer: colibactin makes its mark},
  author={Janelle C. Arthur},
  journal={Nature Reviews Gastroenterology \& Hepatology},
  year={2020},
  volume={17},
  pages={317-318}
}
  • J. Arthur
  • Published 21 April 2020
  • Biology, Medicine
  • Nature Reviews Gastroenterology & Hepatology
Colibactin-producing bacteria are abundant in the gut microbiota of colorectal cancer tumours and promote colon tumorigenesis in mouse models. Now, a new study demonstrates a direct link between exposure of human intestinal epithelial cells to colibactin and two unique mutational fingerprints found in human colorectal tumours. 

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Recent advances in microbial toxin-related strategies to combat cancer.

Which bacterial toxins are worthy of validation as markers in colorectal cancer screening? A critical review.

In this review, colibactin and Bacteroides fragilis toxin are the best candidates, possibly complemented by the cytotoxic necrotizing factor (CNF) and recommended for prospective evaluation of their true ability to increase the sensitivity of FOBT when combined during general population screening.

Molecular Underpinnings and Environmental Drivers of Spontaneous Loss of Heterozygosity in Drosophila Intestinal Stem Cells

A mechanistic understanding of mitotic recombination in stem cells in vivo, an important mediator of LOH, is provided using whole-genome sequencing of somatic LOH events to demonstrate that they arise primarily via mitosis recombination.

TaxiBGC: a Taxonomy-guided Approach for the Identification of Experimentally Verified Microbial Biosynthetic Gene Clusters in Shotgun Metagenomic Data

Biosynthetic gene clusters (BGCs) in microbial genomes encode for the production of bioactive secondary metabolites (SMs). Given the well-recognized importance of SMs in microbe-microbe and

Detection of pks Island mRNAs Using Toehold Sensors in Escherichia coli

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A distinct mutational signature in colorectal cancer is described and it is implied that the underlying mutational process results directly from past exposure to bacteria carrying the colibactin-producing pks pathogenicity island.

Molecular Basis of Gut Microbiome-Associated Colorectal Cancer: A Synthetic Perspective.

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The human gut bacterial genotoxin colibactin alkylates DNA

Interestingly, the isolation and structural characterization of metabolites from mutant strains of pks+ E. coli revealed that colibactin likely contains a cyclopropane ring, a reactive structural motif found in DNA alkylating natural products, which led to hypothesize that colIBactin may covalently modify DNA.

Colibactin DNA damage signature indicates causative role in colorectal cancer

Interestingly, genomic contexts of DSBs were enriched for AT-rich penta-/hexameric sequence motifs, exhibiting a particularly narrow minor groove width and extremely negative electrostatic potential, which corresponded with the binding characteristics of colibactin to double-stranded DNA, as elucidated by docking and molecular dynamics simulations.

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