Transcriptomic and metabolomic analyses of the antimicrobial activity of phenoxyethanol against phylotype IA1 and II Cutibacterium acnes

AIMS: Phenoxyethanol is a broad-spectrum antimicrobial agent widely used in cosmetic formulations. However, its antibacterial effects on different skin bacteria, particularly the predominant Cutibacterium acnes and its various phylotypes, remain unclear. The objective of this study was to examine the antimicrobial effects of phenoxyethanol on C. acnes and explore the mechanism. METHODS AND RESULTS: Phenoxyethanol exhibited strong antimicrobial effects against both C. acnes ATCC6919 (phylotype IA1) and CCSM0331 (phylotype II), achieving a minimum inhibitory concentration (MIC) of 0.5% (v/v). Sub-MIC concentrations showed a stronger inhibitory effect on CCSM0331. RNA-seq and metabolomic analyses revealed that phenoxyethanol disrupted cell membrane integrity and influenced essential metabolic pathways, such as energy metabolism, amino acid metabolism, and pyrimidine metabolism. Additionally, glycolysis and the Wood-Werkman cycle were inhibited in CCSM0331 but enhanced in ATCC6919. The expression of genes involved in porphyrin metabolism, associated with inflammation, was significantly reduced. CONCLUSIONS: Phenoxyethanol exhibits the antimicrobial activity against C. acnes, with differential effects on phylotypes, targeting critical metabolic pathways and cellular processes. These findings indicate its potential for acne treatment.