Intraspecies warfare restricts strain coexistence in human skin microbiomes.

Determining why only a fraction of encountered or applied bacterial strains engraft in a given person's microbiome is crucial for understanding and engineering these communities1. Previous work has established that metabolism can determine colonization success in vivo2-4, but relevance of bacterial warfare in preventing engraftment has been less explored. Here, we demonstrate that intraspecies warfare presents a significant barrier to strain transmission in the skin microbiome by profiling 14,884 pairwise interactions between Staphylococcus epidermidis cultured from eighteen human subjects from six families. We find that intraspecies antagonisms are abundant; these interactions are mechanistically diverse, independent of the relatedness between strains, and consistent with rapid evolution via horizontal gene transfer. Ability to antagonize more strains is associated with reaching a higher fraction of the on-person S. epidermidis community. Moreover, antagonisms are significantly depleted among strains residing on the same person relative to random assemblages. Two notable exceptions, in which bacteria evolved to become sensitive to antimicrobials found on the same host, are explained by mutations that provide phage resistance, contextualizing the importance of warfare among other lethal selective pressures. Taken together, our results emphasize that accounting for intraspecies bacterial warfare is essential to the design of long-lasting probiotic therapeutics.

Highly-resolved within-species dynamics in the human facial skin microbiome.

Human facial skin microbiomes (FSMs) on adults are dominated by just two bacterial species, Cutibacterium acnes and Staphylococcus epidermidis. Underlying this apparent simplicity, each FSM harbors multiple strains of both species whose assembly dynamics on individuals are unknown. Here, we use 4,055 isolate genomes and 360 metagenomes to trace the dynamics of strains on individuals and their transmission. Strains are shared amongst family members of all ages, but each individual harbors unique strain consortia. Strain stability changes upon formation of the adult-type FSM: S. epidermidis lineage turnover slows, and the rate of C. acnes colonization increases before stabilizing, suggesting this transitional window could facilitate engraftment of therapeutic strains. Our work reveals previously undetectable community dynamics and informs the design of therapeutic interventions.