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Porphyrin production and regulation in different Propionibacterium acnes lineages contribute to acne vulgaris pathogenesis

Abstract

Propionibacterium acnes is a dominant human skin commensal. It has been implicated in acne pathogenesis, but its role remains unclear. Recent metagenomic studies have revealed that certain P. acnes strains are highly associated with acne, while some others are associated with healthy skin. Little information exists about P. acnes strain-level differences beyond the genomic differences. In this study, I revealed that acne-associated type IA P. acnes strains produced significantly higher levels of porphyrins (a metabolite important in acne development) than health-associated strains (type II). Strains of type IA-1 and type IA-2 produced similar levels of porphyrins. Moreover, porphyrin production in these P. acnes strains is modulated by vitamin B12. On the other hand, health-associated type II strains produced low levels of porphyrins and did not respond to vitamin B12. Strains from other lineages (type IB and type III) have lower levels of porphyrin production and porphyrin levels were not modulated by vitamin B12. Using small molecule substrates and inhibitors, I demonstrated that porphyrin biosynthesis was modulated at the metabolic level in type IA strains. By comparing the porphyrin operons of different strains, I identified a repressor gene (deoR) of porphyrin biosynthesis that was encoded in all health-associated P. acnes type II strains, types IB-3, IC, and III strains, but not in acne-associated type IA strains. The expression of deoR suggests regulation of porphyrin production at the transcriptional level in health-associated strains. Other skin propionibacteria, Propionibacterium granulosum, Propionibacterium avidum, and Propionibacterium humerusii, produced little or no porphyrin, and were not regulated by vitamin B12. Additionally, I developed an assay using mass spectrometry to analyze porphyrin levels in skin samples. The findings from my study provide a potential molecular explanation for the different contributions of P. acnes strains to skin health and disease, and support the role of vitamin B12 in acne pathogenesis in a subset of the population. This study emphasizes the importance of understanding the role of the commensal microbial community in health and disease at the strain level, and suggests potential utility of health-associated P. acnes strains in acne treatment.

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