The Polyamine Spermidine Modulates the Production of the Bacterial Genotoxin Colibactin

Open access
Date
2019Type
- Journal Article
Citations
Cited 11 times in
Web of Science
Cited 13 times in
Scopus
ETH Bibliography
yes
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Abstract
Colibactin is a polyketide/nonribosomal peptide produced by Escherichia coli strains that harbor the pks island. This toxin induces DNA double-strand breaks and DNA interstrand cross-links in infected eukaryotic cells. Colibactin-producing strains are found associated with colorectal cancer biopsy specimens and promote intestinal tumor progression in various murine models. Polyamines are small polycationic molecules produced by both microorganisms and eukaryotic cells. Their levels are increased in malignancies, where they contribute to disease progression and metastasis. In this study, we demonstrated that the endogenous spermidine synthase SpeE is required for full genotoxic activity of colibactin-producing E. coli. Supplying spermidine in a ΔspeE pks+ E. coli strain restored genotoxic activity. Spermidine is involved in the autotoxicity linked to colibactin and is required for direct damaging activity on DNA. The production of the colibactin prodrug motif is impaired in ΔspeE mutants. Therefore, we demonstrated that spermidine has a direct impact on colibactin synthesis. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000370492Publication status
publishedExternal links
Journal / series
mSphereVolume
Pages / Article No.
Publisher
American Society for MicrobiologySubject
Escherichia coli; biosynthesis; colorectal cancer; genotoxic colibactin; polyaminesOrganisational unit
03980 - Piel, Jörn / Piel, Jörn
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Show all metadata
Citations
Cited 11 times in
Web of Science
Cited 13 times in
Scopus
ETH Bibliography
yes
Altmetrics