Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 824-835.e6 |
| Journal | Cell Host and Microbe |
| Volume | 30 |
| Issue number | 6 |
| Online published | 19 Apr 2022 |
| DOIs | |
| Publication status | Published - 8 Jun 2022 |
| Externally published | Yes |
Bibliographical note
Publisher Copyright:© 2022 The Authors
Funding
We thank Siv Ahrné (Lund University, Sweden) for providing L. reuteri R2lc, N2J, N2D, and N4I; BioGaia AB (Stockholm, Sweden) for providing L. reuteri strains ATCC PTA 6475; and Joseph Skarlupka for technical assistance. We are grateful to the College of Agricultural Life Sciences (CALS) Statistical Consulting Lab for their assistance in the statistical analysis and the University of Wisconsin Biotechnology Center DNA Sequencing Facility for their services. We thank O'Reilly Science Art for assistance with preparing the graphical abstract. This work was supported by startup funds from the University of Wisconsin-Madison to J.-P.v.P. the UW-Madison Food Research Institute, and the United States Department of Agriculture, National Institute of Food and Agriculture (USDA NIFA) Hatch award MSN185615 and grant no. 2018-6717-27523. M.Ö. received financial support from the Turkish Ministry of National Education and from the UW-Madison Department of Food Science. M.Ö. and S.Z. were the recipients of the Robert H. and Carol L. Deibel Distinguished Graduate Fellowship in probiotic research, which was awarded by the UW-Madison Food Research Institute. J.C. is supported by National Institutes of Health grant R01 AI153173. Gnotobiotic work was partly supported by the Office of the Vice-Chancellor for Research and Graduate Education at the University of Wisconsin-Madison, with funding from the Wisconsin Alumni Research Foundation. Conceptualization, M.Ö. and J.-P.V.P.; methodology, M.Ö. J.-H.O. R.T. D.A. E.V. F.E.R. and J.-P.V.P.; formal analysis, M.Ö. J.-H.O. R.T. D.A. S.Z. and T.J.A.; investigation, M.Ö. J.-H.O. R.T. S.Z. T.J.A. M.H. F.L. and J.C.; writing – original draft, M.Ö. J.W. and J.-P.V.P.; writing – review & editing, M.Ö. and J.-P.V.P.; visualization, M.Ö. J.-H.O. and S.Z.; validation, R.T. D.A. T.J.A. M.H. S.R.-R. and C.C.C.; resources, F.E.R. T.B. and J.W.; supervision, T.B. J.W. J.-P.V.P.; project administration, J.-P.V.P.; funding acquisition, J.-P.V.P. J.-P.V.P. received unrestricted funds from BioGaia AB, a probiotic-producing company. J.-P.V.P. is the founder of the consulting company Next-Gen Probiotics. J.W. has received grants and honoraria from several food and ingredient companies, including companies that produce probiotics. J.W. is a co-owner of Synbiotic Solutions, and is on the Scientific Advisory Board of Alimentary Health. M.Ö. was an employee of DuPont Nutrition and Biosciences. J.C. is a Scientific Advisor for Seed Health, Inc. We thank Siv Ahrné (Lund University, Sweden) for providing L. reuteri R2lc, N2J, N2D, and N4I; BioGaia AB (Stockholm, Sweden) for providing L. reuteri strains ATCC PTA 6475; and Joseph Skarlupka for technical assistance. We are grateful to the College of Agricultural Life Sciences (CALS) Statistical Consulting Lab for their assistance in the statistical analysis and the University of Wisconsin Biotechnology Center DNA Sequencing Facility for their services. We thank O’Reilly Science Art for assistance with preparing the graphical abstract. This work was supported by startup funds from the University of Wisconsin-Madison to J.-P.v.P., the UW-Madison Food Research Institute , and the United States Department of Agriculture , National Institute of Food and Agriculture (USDA NIFA) Hatch award MSN185615 and grant no. 2018-6717-27523 . M.Ö. received financial support from the Turkish Ministry of National Education and from the UW-Madison Department of Food Science . M.Ö. and S.Z. were the recipients of the Robert H. and Carol L. Deibel Distinguished Graduate Fellowship in probiotic research, which was awarded by the UW-Madison Food Research Institute . J.C. is supported by National Institutes of Health grant R01 AI153173 . Gnotobiotic work was partly supported by the Office of the Vice-Chancellor for Research and Graduate Education at the University of Wisconsin-Madison, with funding from the Wisconsin Alumni Research Foundation .
Research Keywords
- acetylation
- acyltransferase
- antimicrobial
- biosynthetic gene clusters
- gut symbiont
- Limosilactobacillus reuteri
- microbial competition
- microbial ecology
- polyene
- polyketide
- secondary metabolite
Publisher's Copyright Statement
- This full text is made available under CC-BY-NC-ND 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/
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