Gut symbionts Lactobacillus reuteri R2lc and 2010 encode a polyketide synthase cluster that activates the mammalian aryl hydrocarbon receptor

Özçam, M., Tocmo, R. ORCID: https://orcid.org/0009-0007-4850-977X, Oh, J.-H., Afrazi, A., Mezrich, J. D., Roos, S., Claesen, J. and van Pijkeren, J.-P. (2019) Gut symbionts Lactobacillus reuteri R2lc and 2010 encode a polyketide synthase cluster that activates the mammalian aryl hydrocarbon receptor. Applied and Environmental Microbiology, 85 (10). e01661-18. ISSN 1098-5336 doi: 10.1128/aem.01661-18

Abstract/Summary

A mechanistic understanding of microbe-host interactions is critical to developing therapeutic strategies for targeted modulation of the host immune system. Different members of the gut symbiont species Lactobacillus reuteri modulate host health by, for example, reduction of intestinal inflammation. Previously, it was shown that L. reuteri activates the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that plays an important role in the mucosal immune system, by the production of tryptophan catabolites. Here, we identified a novel pathway by which L. reuteri activates AhR, which is independent of tryptophan metabolism. We screened a library of 36 L. reuteri strains and determined that R2lc and 2010, strains with a pigmented phenotype, are potent AhR activators. By whole-genome sequencing and comparative genomics, we identified genes unique to R2lc and 2010. Our analyses demonstrated that R2lc harbors two genetically distinct polyketide synthase (PKS) clusters, functionally unknown (fun) and pks, each carried by a multicopy plasmid. Inactivation of pks, but not fun, abolished the ability of R2lc to activate AhR. L. reuteri 2010 has a gene cluster homologous to the pks cluster in R2lc with an identical gene organization, which is also responsible for AhR activation. In conclusion, we identified a novel PKS pathway in L. reuteri R2lc and 2010 that is responsible for AhR activation.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/117203
Identification Number/DOI	10.1128/aem.01661-18
Refereed	Yes
Divisions	No Reading authors. Back catalogue items Life Sciences > School of Chemistry, Food and Pharmacy > Department of Food and Nutritional Sciences > Food Microbial Sciences Research Group
Publisher	American Society for Microbiology
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