The genotoxin colibactin
Résumé
Escherichia coli is a commensal inhabitant of the lower gastrointestinal tract of humans where it is the predominant facultative anaerobic organism. E. coli also belongs to the initial microbiota that colonizes the mammalian gut. Infants are stably colonized by E. coli within a few days after birth. Certain E. coli strains display enhanced ability to cause infection outside the intestinal tract. These extra-intestinal pathogenic E. coli (ExPEC) carry specific genetic determinants or virulence factors that are clustered on genomic islands. We have shown that a subset of ExPEC isolates harbor a genomic island, the pks island, which codes for the production of colibactin, a polyketide-non ribosomal peptide genotoxin. Colibactin production is not restricted to E. coli strains isolated from extra-intestinal infections. Commensal E. coli strains harboring the pks island are ubiquitous in the urban population of industrialized countries. Studies have focused on the impact of colibactin on host cells in vitro and in vivo. The production of colibactin was indeed demonstrated to generate DNA double strand breaks and host cell cycle arrest. Moreover, we recently showed that renewal of the mature intestinal epithelium depends on neonate gut residents and how critical is the synthesis of colibactin by commensal E. coli strain colonizing the newborn. Recent data also indicate that pks+ E. coli strains induce genomic instability and cellular senescence, which could induce carcinogenesis. On the other hand, we have also shown that the pks island is required for the colonic anti-inflammatory properties of a clinically efficient probiotic that is used empirically since almost one century (E. coli Nissle 1917). This Yin-Yang effect of colibactin could result from the production of heterogeneous compounds with different biological activities by the pks island-encoded biosynthetic pathway.
Domaines
Sciences du Vivant [q-bio]
Origine : Fichiers produits par l'(les) auteur(s)
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