C. acnes phage predation in the healthy human skin microbiome

Poor predictability of stable microbial colonization undermines our ability to harness probiotics and phage therapy in human health applications. Person-specific diversity contributes to this unpredictability; it is unclear how microbes colonize and evolve on individuals to create microbiomes with unique compositions, in which most genetic variation occurs within species boundaries. Bacteria-phage dynamics are implicated in promoting microbiome diversity by generating species- and strain-level population fluctuations. Yet, much remains unknown about the assembly and structure of phage populations in human ecosystems, and consequently their role in stable microbial colonization. What role do existing prophage and/or free phage play in the success of new bacterial colonization? How are phage populations structured, and is prophage carriage a source of acquisition? Sebaceous skin offers a tractable model to unravel phage population structure due to its low species-level complexity, ease of temporospatial sampling, and selective conduciveness to colonization at different human developmental stages. Here, we combine a culture-based whole genome sequencing and shotgun metagenomic approach to examine the coevolutionary dynamics of the highly abundant and ubiquitous skin commensal Cutibacterium acnes and its phage. We begin by screening for prophages in our collection of 3,794 whole genome sequenced C. acnes isolates sampled from human skin. We find that the frequency of prophage carriage is low in C. acnes; in 1.27% of isolates the well-characterized dsDNA pseudolysogen is detected and in 5% of isolates a novel ssDNA lysogen is detected. Interestingly, we find that neither phage co-occur within a single bacterial genome, and that the set of isolates collected from an individual tend to be dominated by a single phage type. When age is considered, we find that adolescent and younger individuals tend to carry the ssDNA lysogen more than adults, who carry the dsDNA pseudolysogen at a higher frequency. This result is recapitulated in our metagenomic samples, where we also observed that the relative abundance of C. acnes bacteria increases with age. The possible relationship between this age-based increase in C. acnes bacterial abundance and differences in prophage carriage is the topic of further investigation. Overall, these findings support future studies into the role of prophages and phage predation in the colonization of the skin microbiome.