Strain-Level Differences in Porphyrin Production and Regulation in <named-content content-type="genus-species">Propionibacterium acnes</named-content> Elucidate Disease Associations

ABSTRACT Propionibacterium acnes is an important skin commensal, but it is also considered a pathogenic factor in several diseases including acne vulgaris, the most common skin disease. While previous studies have revealed P. acnes strain-level differences in health and disease associations, the und...

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Auteurs principaux:	Tremylla Johnson, Dezhi Kang, Emma Barnard, Huiying Li
Format:	article
Langue:	EN
Publié:	American Society for Microbiology 2016
Sujets:	porphyrin vitamin B12 Propionibacterium acnes strain acne 5-aminolevulinic acid Microbiology QR1-502
Accès en ligne:	https://doaj.org/article/93c0566ba65a4a6ab6b056bc225a75c8
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spelling	oai:doaj.org-article:93c0566ba65a4a6ab6b056bc225a75c82021-11-15T15:21:39ZStrain-Level Differences in Porphyrin Production and Regulation in <named-content content-type="genus-species">Propionibacterium acnes</named-content> Elucidate Disease Associations10.1128/mSphere.00023-152379-5042https://doaj.org/article/93c0566ba65a4a6ab6b056bc225a75c82016-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00023-15https://doaj.org/toc/2379-5042ABSTRACT Propionibacterium acnes is an important skin commensal, but it is also considered a pathogenic factor in several diseases including acne vulgaris, the most common skin disease. While previous studies have revealed P. acnes strain-level differences in health and disease associations, the underlying molecular mechanisms remain unknown. Recently, we demonstrated that vitamin B12 supplementation increases P. acnes production of porphyrins, a group of proinflammatory metabolites important in acne development (D. Kang, B. Shi, M. C. Erfe, N. Craft, and H. Li, Sci. Transl. Med. 7:293ra103, 2015, doi:10.1126/scitranslmed.aab2009). In this study, we compared the porphyrin production and regulation of multiple P. acnes strains. We revealed that acne-associated type IA-2 strains inherently produced significantly higher levels of porphyrins, which were further enhanced by vitamin B12 supplementation. On the other hand, health-associated type II strains produced low levels of porphyrins and did not respond to vitamin B12. Using a small-molecule substrate and inhibitor, we demonstrated that porphyrin biosynthesis was modulated at the metabolic level. We identified a repressor gene (deoR) of porphyrin biosynthesis that was carried in all health-associated type II strains, but not in acne-associated type IA-2 strains. The expression of deoR suggests additional regulation of porphyrin production at the transcriptional level in health-associated strains. Our findings provide one potential molecular mechanism for the different contributions of P. acnes strains to skin health and disease and support the role of vitamin B12 in acne pathogenesis. Our 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. IMPORTANCE Propionibacterium acnes is a dominant bacterium residing on skin, and it has been thought to play a causal role in several diseases including acne, a common skin disease affecting more than 80% of people worldwide. While specific strains of P. acnes have been associated with either disease or healthy skin, the mechanisms remain unclear. Recently, we showed that vitamin B12 supplementation increased porphyrin production in P. acnes, leading to acne development (D. Kang, B. Shi, M. C. Erfe, N. Craft, and H. Li, Sci. Transl. Med. 7:293ra103, 2015, doi:10.1126/scitranslmed.aab2009). Here, we reveal that the levels of porphyrin production and vitamin B12 regulation are different between acne- and health-associated strains, suggesting a potential molecular mechanism for disease-associated strains in acne pathogenesis and for health-associated strains in skin health. This study highlights the importance of understanding the strain-level differences of the human microbiota in disease pathogenesis. Our findings also suggest the porphyrin biosynthesis pathway as a candidate drug target and use of health-associated strains as potential probiotics in novel acne therapeutics.Tremylla JohnsonDezhi KangEmma BarnardHuiying LiAmerican Society for Microbiologyarticleporphyrinvitamin B12Propionibacterium acnesstrainacne5-aminolevulinic acidMicrobiologyQR1-502ENmSphere, Vol 1, Iss 1 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	porphyrin vitamin B12 Propionibacterium acnes strain acne 5-aminolevulinic acid Microbiology QR1-502
spellingShingle	porphyrin vitamin B12 Propionibacterium acnes strain acne 5-aminolevulinic acid Microbiology QR1-502 Tremylla Johnson Dezhi Kang Emma Barnard Huiying Li Strain-Level Differences in Porphyrin Production and Regulation in <named-content content-type="genus-species">Propionibacterium acnes</named-content> Elucidate Disease Associations
description	ABSTRACT Propionibacterium acnes is an important skin commensal, but it is also considered a pathogenic factor in several diseases including acne vulgaris, the most common skin disease. While previous studies have revealed P. acnes strain-level differences in health and disease associations, the underlying molecular mechanisms remain unknown. Recently, we demonstrated that vitamin B12 supplementation increases P. acnes production of porphyrins, a group of proinflammatory metabolites important in acne development (D. Kang, B. Shi, M. C. Erfe, N. Craft, and H. Li, Sci. Transl. Med. 7:293ra103, 2015, doi:10.1126/scitranslmed.aab2009). In this study, we compared the porphyrin production and regulation of multiple P. acnes strains. We revealed that acne-associated type IA-2 strains inherently produced significantly higher levels of porphyrins, which were further enhanced by vitamin B12 supplementation. On the other hand, health-associated type II strains produced low levels of porphyrins and did not respond to vitamin B12. Using a small-molecule substrate and inhibitor, we demonstrated that porphyrin biosynthesis was modulated at the metabolic level. We identified a repressor gene (deoR) of porphyrin biosynthesis that was carried in all health-associated type II strains, but not in acne-associated type IA-2 strains. The expression of deoR suggests additional regulation of porphyrin production at the transcriptional level in health-associated strains. Our findings provide one potential molecular mechanism for the different contributions of P. acnes strains to skin health and disease and support the role of vitamin B12 in acne pathogenesis. Our 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. IMPORTANCE Propionibacterium acnes is a dominant bacterium residing on skin, and it has been thought to play a causal role in several diseases including acne, a common skin disease affecting more than 80% of people worldwide. While specific strains of P. acnes have been associated with either disease or healthy skin, the mechanisms remain unclear. Recently, we showed that vitamin B12 supplementation increased porphyrin production in P. acnes, leading to acne development (D. Kang, B. Shi, M. C. Erfe, N. Craft, and H. Li, Sci. Transl. Med. 7:293ra103, 2015, doi:10.1126/scitranslmed.aab2009). Here, we reveal that the levels of porphyrin production and vitamin B12 regulation are different between acne- and health-associated strains, suggesting a potential molecular mechanism for disease-associated strains in acne pathogenesis and for health-associated strains in skin health. This study highlights the importance of understanding the strain-level differences of the human microbiota in disease pathogenesis. Our findings also suggest the porphyrin biosynthesis pathway as a candidate drug target and use of health-associated strains as potential probiotics in novel acne therapeutics.
format	article
author	Tremylla Johnson Dezhi Kang Emma Barnard Huiying Li
author_facet	Tremylla Johnson Dezhi Kang Emma Barnard Huiying Li
author_sort	Tremylla Johnson
title	Strain-Level Differences in Porphyrin Production and Regulation in <named-content content-type="genus-species">Propionibacterium acnes</named-content> Elucidate Disease Associations
title_short	Strain-Level Differences in Porphyrin Production and Regulation in <named-content content-type="genus-species">Propionibacterium acnes</named-content> Elucidate Disease Associations
title_full	Strain-Level Differences in Porphyrin Production and Regulation in <named-content content-type="genus-species">Propionibacterium acnes</named-content> Elucidate Disease Associations
title_fullStr	Strain-Level Differences in Porphyrin Production and Regulation in <named-content content-type="genus-species">Propionibacterium acnes</named-content> Elucidate Disease Associations
title_full_unstemmed	Strain-Level Differences in Porphyrin Production and Regulation in <named-content content-type="genus-species">Propionibacterium acnes</named-content> Elucidate Disease Associations
title_sort	strain-level differences in porphyrin production and regulation in <named-content content-type="genus-species">propionibacterium acnes</named-content> elucidate disease associations
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/93c0566ba65a4a6ab6b056bc225a75c8
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Strain-Level Differences in Porphyrin Production and Regulation in <named-content content-type="genus-species">Propionibacterium acnes</named-content> Elucidate Disease Associations

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