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Review
. 2018 Apr 10;10(4):151.
doi: 10.3390/toxins10040151.

Colibactin: More Than a New Bacterial Toxin

Tiphanie Faïs  1   2 , Julien Delmas  3   4 , Nicolas Barnich  5 , Richard Bonnet  6   7 , Guillaume Dalmasso  8
Affiliations
Review

Colibactin: More Than a New Bacterial Toxin

Tiphanie Faïs et al. Toxins (Basel). .

Abstract

Cyclomodulins are bacterial toxins that interfere with the eukaryotic cell cycle. A new cyclomodulin called colibactin, which is synthetized by the pks genomic island, was discovered in 2006. Despite many efforts, colibactin has not yet been purified, and its structure remains elusive. Interestingly, the pks island is found in members of the family Enterobacteriaceae (mainly Escherichia coli and Klebsiella pneumoniae) isolated from different origins, including from intestinal microbiota, septicaemia, newborn meningitis, and urinary tract infections. Colibactin-producing bacteria induce chromosomal instability and DNA damage in eukaryotic cells, which leads to senescence of epithelial cells and apoptosis of immune cells. The pks island is mainly observed in B2 phylogroup E. coli strains, which include extra-intestinal pathogenic E. coli strains, and pksE. coli are over-represented in biopsies isolated from colorectal cancer. In addition, pksE. coli bacteria increase the number of tumours in diverse colorectal cancer mouse models. Thus, colibactin could have a major impact on human health. In the present review, we will focus on the biological effects of colibactin, the distribution of the pks island, and summarize what is currently known about its synthesis and its structure.

Keywords: E. coli; cancer; colibactin; microbiota; pks; toxin.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Example of molecules synthetized by the hybrid non-ribosomal peptide synthetase-polyketide synthase (NRPS-PKS) assembly lines.
Figure 2
Figure 2
Organization of the pks island. Adapted from Reference [2].
Figure 3
Figure 3
Schematic representation of colibactin biosynthesis. Adapted from Reference [39]. (A) First steps of colibactin synthesis. (B) Cyclopropane formation. (C) Thiazole ring formation.
Figure 4
Figure 4
Proposed model for final maturation of colibactin. ClbM takes charge of the prodrug, and releases it into the periplasm, where ClbP generates by cleavage the mature colibactin. ClbS is able to sequester and inactivate any colibactin presents in the cytoplasm, therefore protecting bacterial DNA.
Figure 5
Figure 5
Structure of isolated, predicted, and synthetized precolibactins. Adapted from Reference [40]. Blue boxes represent cyclopropane structures responsible for DNA-alkylation. Red boxes represent bithiazole motifs which are likely able to intercalate DNA.
See this image and copyright information in PMC

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