A secondary metabolite drives intraspecies antagonism in a gut symbiont that is inhibited by cell-wall acetylation

Özçam, M., Oh, J.-H., Tocmo, R. ORCID: https://orcid.org/0009-0007-4850-977X, Acharya, D., Zhang, S., Astmann, T. J., Heggen, M., Ruiz-Ramírez, S., Li, F., Cheng, C. C., Vivas, E., Rey, F. E., Claesen, J., Bugni, T. S., Walter, J. and van Pijkeren, J.-P. (2022) A secondary metabolite drives intraspecies antagonism in a gut symbiont that is inhibited by cell-wall acetylation. Cell Host & Microbe, 30 (6). pp. 824-835. ISSN 1934-6069 doi: 10.1016/j.chom.2022.03.033

Abstract/Summary

The mammalian microbiome encodes numerous secondary metabolite biosynthetic gene clusters; yet, their role in microbe-microbe interactions is unclear. Here, we characterized two polyketide synthase gene clusters (fun and pks) in the gut symbiont Limosilactobacillus reuteri. The pks, but not the fun, cluster encodes antimicrobial activity. Forty-one of 51 L. reuteri strains tested are sensitive to Pks products; this finding was independent of strains’ host origin. Sensitivity to Pks was also established in intraspecies competition experiments in gnotobiotic mice. Comparative genome analyses between Pks-resistant and -sensitive strains identified an acyltransferase gene (act) unique to Pks-resistant strains. Subsequent cell-wall analysis of wild-type and act mutant strains showed that Act acetylates cell-wall components, providing resistance to Pks-mediated killing. Additionally, pks mutants lost their competitive advantage, while act mutants lost their Pks resistance in in vivo competition assays. These findings provide insight into how closely related gut symbionts can compete and co-exist in the gastrointestinal tract.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/117257
Identification Number/DOI	10.1016/j.chom.2022.03.033
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	Elsevier
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