Genetic and Functional Analyses of Cutibacterium Acnes Isolates Reveal the Association of a Linear Plasmid with Skin Inflammation.

Abstract

Cutibacterium acnes is a commensal bacterium on the skin that is generally well-tolerated, but different strain types have been hypothesized to contribute to the disease acne vulgaris. To understand how some strain types might contribute to skin inflammation, we generated a repository of C. acnes isolates from skin swabs of healthy subjects and subjects with acne and assessed their strain-level identity and capacity to stimulate cytokine release. Phylotype II K-type strains were more frequent on healthy and nonlesional skin of subjects with acne than those isolated from lesions. Phylotype IA-1 C-type strains were increased on lesional skin compared with those on healthy skin. The capacity to induce cytokines from cultured monocyte-derived dendritic cells was opposite to this action on sebocytes and keratinocytes and did not correlate with the strain types associated with the disease. Whole-genome sequencing revealed a linear plasmid in high-inflammatory isolates within similar strain types that had different proinflammatory responses. Single-cell RNA sequencing of mouse skin after intradermal injection showed that strains containing this plasmid induced a higher inflammatory response in dermal fibroblasts. These findings revealed that C. acnes strain type is insufficient to predict inflammation and that carriage of a plasmid could contribute to disease.

• Authors: Alan M O'Neill, Kellen J Cavagnero, Jason S Seidman, Livia Zaramela, Yang Chen, Fengwu Li, Teruaki Nakatsuji, Joyce Y Cheng, Yun L Tong, Tran H Do, Samantha L Brinton, Tissa R Hata, Robert L Modlin, Richard L Gallo
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 144 Issue 1 Pg. 116-124.e4 (01 2024) ISSN: 1523-1747 [Electronic] United States
• PMID: 37478901 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2023. Published by Elsevier Inc.

Chemical References

• Cytokines

Topics

• Animals
• Mice
• Humans
• Skin (microbiology)
• Acne Vulgaris (microbiology)
• Dermatitis
• Propionibacterium acnes (genetics)
• Plasmids (genetics)
• Inflammation
• Cytokines (genetics)