Gut symbionts from distinct hosts exhibit genotoxic activity via divergent colibactin biosynthetic pathways.

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Version: Final published version
Serval ID
serval:BIB_721F6FBC81D9
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Gut symbionts from distinct hosts exhibit genotoxic activity via divergent colibactin biosynthetic pathways.
Journal
Applied and Environmental Microbiology
Author(s)
Engel P., Vizcaino M.I., Crawford J.M.
ISSN
1098-5336 (Electronic)
ISSN-L
0099-2240
Publication state
Published
Issued date
2015
Volume
81
Number
4
Pages
1502-1512
Language
english
Notes
Publication types: 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, inflicting DNA damage upon eukaryotic cells and contributing 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.
Pubmed
Web of science
Open Access
Yes
Create date
06/03/2015 19:12
Last modification date
20/08/2019 14:30
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