Oleum cinnamomi disrupts Cutibacterium acnes adhesion and metabolism by covalently targeting enolase and coenzyme A.

BACKGROUND

Preventing Cutibacterium acnes (C. acnes) adhesion to human skin is essential for acne control, yet the molecular determinants of adhesion-associated drug resistance remain undefined and no pharmacological agents specifically blocking C. acnes attachment are available.

OBJECTIVE

To evaluate oleum cinnamomi (OC), a natural cinnamon oil, as a potential anti-adhesive modality against C. acnes.

METHODS

In vitro antibacterial assays, quantitative chemoproteomics, and keratinocyte infection models were integrated to quantify OC-mediated inhibition of C. acnes adhesion and biofilm formation, map covalent targets of OC electrophiles cinnamaldehyde (CA) and 2-methoxycinnamaldehyde (MCA), and delineate downstream metabolic perturbations via untargeted metabolomics and redox profiling.

RESULTS

OC, CA and MCA concentration-dependently reduced C. acnes adhesion (> 80%) without rapid bactericidal activity. Both CA and MCA covalently modified Cys359 of enolase (ENO), suppressing glycolytic flux and ATP generation. Independently, CA formed a thiohemiacetal adduct with coenzyme A (CoA), blocking acyl-transfer reactions required for fatty-acid metabolism and membrane biogenesis. The combined effects elevated the NADH/NAD+ ratio, disrupted oligosaccharide homeostasis, and impaired biofilm exopolysaccharide biosynthesis with altered monosaccharide composition, thereby compromising biofilm formation and driving C. acnes into a metabolically compromised state.

CONCLUSION

OC-derived electrophiles act as metabolic modulators that incapacitate C. acnes adhesion and biofilm development through orthogonal inhibition of ENO and CoA-dependent pathways, providing a mechanistic blueprint for potential topical anti-acne therapies that circumvent conventional antibiotic resistance.