Intraspecies warfare restricts strain coexistence in human skin microbiomes

Determining why only a fraction of encountered or applied strains engraft in a given person's microbiome is crucial for understanding and engineering these communities. Previous work has established that metabolic competition between bacteria can restrict colonization success in vivo, but other mechanisms may also prevent successful engraftment. Here we combine genomic analysis and high-throughput agar competition assays to demonstrate that intraspecies warfare presents a significant barrier to strain coexistence in the human skin microbiome by profiling 14,884 pairwise interactions between Staphylococcus epidermidis isolates cultured from 18 people from 6 families. We find that intraspecies antagonisms are abundant, mechanistically diverse, independent of strain relatedness and consistent with rapid evolution via horizontal gene transfer. Critically, these antagonisms are significantly depleted among strains residing on the same person relative to random assemblages, indicating a significant in vivo role. Wide variation in antimicrobial production and resistance suggests trade-offs between these factors and other fitness determinants. Together, our results emphasize that accounting for intraspecies warfare may be essential to the design of long-lasting probiotic therapeutics.