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 out of 51 L. reuteri strains tested are sensitive to Pks products, which was independent of strains’ host origin. The 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) that is unique to Pks-resistant strains. Subsequent peptidoglycan analysis of the wild-type and the act mutant strains showed that Act acetylates peptidoglycan. The pks mutants lost their competitive advantage and act mutants lost their Pks resistance in vivo. Thus, our findings provide mechanistic insights into how closely related gut symbionts can compete and co-exist in the gastrointestinal tract.
Competing Interest Statement
JPVP received unrestricted funds from BioGaia, AB, a probiotic-producing company. JPVP is the founder of the consulting company Next-Gen Probiotics, LLC. JW has received grants and honoraria from several food and ingredient companies, including companies that produce probiotics. JW is a co-owner of Synbiotic Solutions, LLC, and is on the Scientific Advisory Board of Alimentary Health. M.O. was an employee of DuPont Nutrition and Biosciences. JC is a Scientific Advisor for Seed Health, Inc.
