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Gut symbionts from distinct hosts exhibit genotoxic activity via divergent colibactin biosynthesis pathways. | LitMetric

AI Article Synopsis

  • * The study focused on colibactin, a secondary metabolite from Escherichia coli that can damage DNA and is linked to colorectal cancer, and found a homologous biosynthetic pathway in Frischella perrara, a bacteria associated with honey bees.
  • * Comparative analyses indicated that both F. perrara and E. coli produce similar colibactin metabolites and cause DNA damage in eukaryotic cells, suggesting that the

Article Abstract

Secondary metabolites produced by nonribosomal peptide synthetase (NRPS) or polyketide synthase (PKS) pathways are chemical mediators of microbial interactions in diverse environments. However, little is known about their distribution, evolution, and functional roles in bacterial symbionts associated with animals. A prominent example is colibactin, a largely unknown family of secondary metabolites produced by Escherichia coli via a hybrid NRPS-PKS biosynthetic pathway that inflicts DNA damage upon eukaryotic cells and contributes to colorectal cancer and tumor formation in the mammalian gut. Thus far, homologs of this pathway have only been found in closely related Enterobacteriaceae, while a divergent variant of this gene cluster was recently discovered in a marine alphaproteobacterial Pseudovibrio strain. Herein, we sequenced the genome of Frischella perrara PEB0191, a bacterial gut symbiont of honey bees and identified a homologous colibactin biosynthetic pathway related to those found in Enterobacteriaceae. We show that the colibactin genomic island (GI) has conserved gene synteny and biosynthetic module architecture across F. perrara, Enterobacteriaceae, and the Pseudovibrio strain. Comparative metabolomics analyses of F. perrara and E. coli further reveal that these two bacteria produce related colibactin pathway-dependent metabolites. Finally, we demonstrate that F. perrara, like E. coli, causes DNA damage in eukaryotic cells in vitro in a colibactin pathway-dependent manner. Together, these results support that divergent variants of the colibactin biosynthetic pathway are widely distributed among bacterial symbionts, producing related secondary metabolites and likely endowing its producer with functional capabilities important for diverse symbiotic associations.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4309719PMC
http://dx.doi.org/10.1128/AEM.03283-14DOI Listing

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