Biological Evaluation of the Antibacterial Retinoid CD437 in Cutibacterium acnes Infection

Xiao Wen Huang, Wen Pan, Mei Zhen Zhong, Yashpal Singh Chhonker, Andrew D. Steele, Colleen E. Keohane, Biswajit Mishra, Lewis Oscar Felix Raj Lucas, Daryl J. Murry, Frederick M. Ausubel, William M. Wuest, Chang Xing Li, Eleftherios Mylonakis

Research output: Contribution to journalArticlepeer-review


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

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalAntimicrobial Agents and Chemotherapy
Issue number4
StatePublished - Apr 2023


  • CD437
  • acne
  • inflammation
  • irritation

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases


Dive into the research topics of 'Biological Evaluation of the Antibacterial Retinoid CD437 in Cutibacterium acnes Infection'. Together they form a unique fingerprint.

Cite this