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.

哺乳动物微生物组编码许多次生代谢物生物合成基因簇；然而，它们在微生物-微生物相互作用中的作用尚不清楚。在这里，我们表征了肠道共生体Limosilactobacillus reuteri中的两个聚酮合酶基因簇（fun和pks ） 。pks而非fun簇编码抗菌活性。测试的 51 个罗伊氏乳杆菌菌株中有 41 个对 Pks 产品敏感；这一发现与菌株的宿主来源无关。对 Pks 的敏感性也在知生小鼠的种内竞争实验中建立。Pks 抗性和敏感菌株之间的比较基因组分析确定了一个酰基转移酶基因（行动) 独特的 Pks 抗性菌株。随后对野生型和act突变菌株的细胞壁分析表明，Act 乙酰化细胞壁成分，提供对 Pks 介导的杀伤的抗性。此外，pks突变体失去了竞争优势，而act突变体在体内竞争测定中失去了 Pks 抗性。这些发现提供了对密切相关的肠道共生体如何在胃肠道中竞争和共存的见解。