The diversity and host interactions of Propionibacterium acnes bacteriophages on human skin

Abstract

The viral population, including bacteriophages, is an important component of the human microbiota, yet is poorly understood. We aim to determine whether bacteriophages modulate the composition of the bacterial populations, thus potentially playing a role in health or disease. We investigated the diversity and host interactions of the bacteriophages of Propionibacterium acnes, a major human skin commensal implicated in acne pathogenesis. By sequencing 48 P. acnes phages isolated from acne patients and healthy individuals and by analyzing the P. acnes phage populations in healthy skin metagenomes, we revealed that P. acnes phage populations in the skin microbial community are often dominated by one strain. We also found phage strains shared among both related and unrelated individuals, suggesting that a pool of common phages exists in the human population and that transmission of phages may occur between individuals. To better understand the bacterium-phage interactions in the skin microbiota, we determined the outcomes of 74 genetically defined Propionibacterium strains challenged by 15 sequenced phages. Depending on the Propionibacterium lineage, phage infection can result in lysis, pseudolysogeny, or resistance. In type II P. acnes strains, we found that encoding matching clustered regularly interspaced short palindromic repeat spacers is insufficient to confer phage resistance. Overall, our findings suggest that the prey-predator relationship between bacteria and phages may have a role in modulating the composition of the microbiota. Our study also suggests that the microbiome structure of an individual may be an important factor in the design of phage-based therapy.

The balance of metagenomic elements shapes the skin microbiome in acne and health

“…Our findings are consistent with previous culture-based observation of a higher frequency of P. acnes phage isolated from healthy individuals than acne patients29, suggesting a role for P. acnes phage in acne-free skin, potentially by modulating P. acnes strain populations in the follicular microbiota. Despite being utilized for almost a century in Eastern Europe as a treatment for acne and other diseases59, few studies have been performed to understand the pray-predator interactions and dynamics between Propionibacterium species/strains and P. acnes phage populations in the skin microbial community29. The observation of increased phage abundance in healthy individuals merits further investigation of the role of P. acnes phage in skin health.…”

“…The observed reduction of acne prevalence in older individuals1011 may be a result of increased abundance of P. acnes phage, in addition to changes in the ecological niche such as reduced sebum and thus reduced propionibacteria load in the follicle34. Our findings are consistent with previous culture-based observation of a higher frequency of P. acnes phage isolated from healthy individuals than acne patients29, suggesting a role for P. acnes phage in acne-free skin, potentially by modulating P. acnes strain populations in the follicular microbiota. Despite being utilized for almost a century in Eastern Europe as a treatment for acne and other diseases59, few studies have been performed to understand the pray-predator interactions and dynamics between Propionibacterium species/strains and P. acnes phage populations in the skin microbial community29.…”

“…The observation of increased phage abundance in healthy individuals merits further investigation of the role of P. acnes phage in skin health. Our findings suggest that it is potentially promising to design personalized and strain-specific phage-based treatment that can target specific P. acnes strains and thus shift the strain composition to a healthy skin microbiota29.…”

“…After removal of human DNA sequences and low-quality reads, we obtained an average of 1.08 gigabase pairs (Gbp) per sample (6.9 × 10 7  bp – 4.8 × 10 9  bp), sufficient to cover the microbial diversity of skin samples24. We mapped the cleaned sequencing reads to our reference genome set, which consists of 1,252 bacterial and 272 fungal genomes from the HMP reference genome database and several additional genomes of skin microorganisms: Propionibacterium avidum 2526 , Propionibacterium granulosum 26 , Propionibacterium humerusii 27, and P. acnes bacteriophage2829. To cover different P. acnes strains, we also included the P. acnes pan-genome in the reference19.…”

Experimental metagenomics and ribosomal profiling of the human skin microbiome

“…Viruses are also present on the skin: bacteriophages, in particular, play a crucial role in shaping bacterial communities, [26] but the study of microbiome-virome relationships is still in its infancy. [27][28][29] Although several microbiome studies are unravelling the complementary aspects of the skin microbiome, [28,30] further research is required to truly understand the complex interplay between the host and the resident microbiome.…”