Porphyrin Production and Regulation in Cutaneous Propionibacteria

Abstract

Porphyrins are intermediate metabolites in the biosynthesis of vital molecules, including heme, cobalamin, and chlorophyll. Bacterial porphyrins are known to be proinflammatory, with high levels linked to inflammatory skin diseases. Propionibacterium species are dominant skin commensals and play essential roles in defending against pathogens and in triggering an inflammatory response. To better understand how the inflammatory potential of the skin microbiome may vary depending on its propionibacterial composition, we compared the production levels of porphyrins among Propionibacterium acnes, Propionibacterium granulosum, Propionibacterium avidum, and Propionibacterium humerusii strains. We found that porphyrin production varied among these species, with P. acnes type I strains producing significantly larger amounts of porphyrins than P. acnes type II and III strains and other Propionibacterium species. P. acnes strains that are highly associated with the common skin condition acne vulgaris responded to vitamin B12 supplementation with significantly higher porphyrin production. In contrast, vitamin B12 supplementation had no effect on the porphyrin production of health-associated P. acnes strains and other propionibacteria. We observed low-level porphyrin production in most Propionibacterium strains harboring the deoR repressor gene, with the exception of P. acnes strains belonging to type I clades IB-3 and IC. Our findings shed light on the proinflammatory potential of distinct phylogenetic lineages of P. acnes as well as other resident skin propionibacteria. We demonstrate that the overall species and strain composition is important in determining the metabolic output of the skin microbiome in health and disease.IMPORTANCE Porphyrins are a group of metabolites essential to the biosynthesis of heme, cobalamin, and chlorophyll in living organisms. Bacterial porphyrins can be proinflammatory, with high levels linked to human inflammatory diseases, including the common skin condition acne vulgaris. Propionibacteria are among the most abundant skin bacteria. Variations in propionibacteria composition on the skin may lead to different porphyrin levels and inflammatory potentials. This study characterized porphyrin production in all lineages of Propionibacterium acnes, the most dominant skin Propionibacterium, and other resident skin propionibacteria, including P. granulosum, P. avidum, and P. humerusii We revealed that P. acnes type I strains produced significantly more porphyrins than did type II and III strains and other Propionibacterium species. The findings from this study shed light on the proinflammatory potential of the skin microbiome and can be used to guide the development of effective acne treatments by modulating the skin microbiome and its metabolic activities.