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 pks E. coli are over-represented in biopsies isolated from colorectal cancer. In addition, pks E. 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.
Highlights
Cyclomodulins are bacterial toxins that interfere with the eukaryotic cell cycle
Key Contribution: This review summarizes what is currently known about the bacterial genotoxin
Because pks E. coli are frequently found in gut microbiota [4,5,6] and DNA alterations are associated with cancers, numerous studies have been performed to understand the potential role of these bacteria in colorectal cancer (CRC)
Summary
Cyclomodulins are bacterial toxins that interfere with the eukaryotic cell cycle. Until 2006, three types of cyclomodulins were known in Escherichia coli: two able to inhibit proliferation (cytolethal distending toxin, CDT; and the cycle inhibiting factor, Cif) and one able to promote proliferation (cytotoxic necrotizing factor, CNF) [1]. Colibactin is a natural and genotoxic chemical compound which is synthetized by polyketide synthases, non-ribosomal peptide synthases, and hybrid enzymes encoded by a 54-kb genomic island designated pks [2]. Colibactin-producing E. coli are over-represented in colorectal cancer (CRC) [12,13,14,15] and they increase the number of tumours in various CRC mouse models [14,16,17,18] This toxin could have a significant effect on human health. We will give an overview of what is currently known about the epidemiology of the pks island, and about the synthesis, predictive structure, and biological activities of colibactin
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