Ribotype-dependent growth inhibition and promotion by erythritol in Cutibacterium acnes

Background: The close balance between Cutibacterium acnes and the skin flora, particularly between C. acnes phylotypes, has been suggested to play an important role in the onset of acne. C. acnes has been classified into ribotypes (RTs) based on polymorphisms in its 16S rRNA sequence, with RT4 and RT5 being associated with the onset of acne and RT6 with healthy skin. Aims: The present study investigated the impact of erythritol on the growth of C. acnes strains classified into different RTs and attempted to elucidate the molecular mechanisms underlying its effects. Methods: Culturing tests were performed on several RTs of C. acnes with or without erythritol. A transcriptional analysis of HM554 (RT6) and HM514 (RT5) was also conducted. Results: The growth of RT2 and RT6, RTs associated with healthy skin, was significantly promoted in a medium containing 10% (W/W) erythritol, whereas that of RT1, RT3, RT4, RT5, and RT8, RTs associated with the development of acne, was inhibited. A RNA-seq analysis of HM554 showed that the expression of six genes (EIGs) potentially involved in carbohydrate metabolism was strongly induced by the presence of 10% erythritol (Log₂ fold change >2.0 and p-value <0.05). A comparative expression analysis by qPCR revealed that EIGs other than g3pD were strongly induced by erythritol in HM514, similar to HM554, whereas g3pD was only slightly induced. Conclusion: Erythritol inhibited the growth of RTs associated with acne and promoted that of RTs associated with healthy skin. The enzyme encoded by g3pD may play an important role in the metabolism of erythritol and the dissolution of its growth inhibitory effects on C. acnes.