Biological Evaluation of the Antibacterial Retinoid CD437 in Cutibacterium acnes Infection

• DOI: 10.1128/aac.01679-22
• Publication Date: 2023-03-21T14:07:24Z
• Authors: Xiao-wen Huang; Wen Pan; Mei-zhen Zhong; Yashpal Singh Chh...; Andrew D. Steele; Colleen E. Keohane; Biswajit Mishra; Lewis Oscar Felix...; Daryl J. Murry; Frederick M. Ausubel; William M. Wuest; Chang-xing Li; Eleftherios Mylon...
• Keywords: Propionibacterium Acnes

Acne vulgaris is a complex skin disease involving infection by Cutibacterium acnes, inflammation, and hyperkeratinization. We evaluated the activity of retinoid 6-[3-(adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) 16 other analogs as potential anti-C. acnes compounds found that CD437 displayed highest antimicrobial with an MIC against C. (ATCC 6919 HM-513) 1 μg/mL. demonstrated MBC 2 μg/mL compared to up 64 for adapalene tetracycline, which are commonly used clinically treat acne. Membrane permeability assays exposure ATCC damaged integrity bacterial membranes, this finding was confirmed scanning electron microscopy. Additionally, downregulated expression virulence factors, including genes encoding Christie-Atkins-Munch-Petersen factor (CAMP1), CAMP2, glycerol-ester hydrolase B (GehB), sialidase B, neuraminidase. In mouse model 6919, topical treatment ameliorated lesions reduced burden in situ (P < 0.001). human NHEK primary cells, transcriptional levels coding inflammatory cytokines (interleukin-1α, ~10-fold; interleukin-6, ~20-fold; interleukin-8, ~30-fold; tumor necrosis factor-alpha, ~6-fold) KRT10 (~10-fold), FLG (~4-fold), TGM1 (~2-fold), indicating can diminish inflammation summary, deserves further attention its dual function acne therapeutic potentially acts on both pathogen host.