Abstract

Sapindus saponins extracted from S. mukorossi have been reported to exert antibacterial activities against skin pathogenic bacteria, but their antibacterial mechanism is still at an exploratory stage. The objective of this study was to explore the synergistic antibacterial mechanism of the combination of two Sapindus saponins, namely Sapindoside A and B (S AB ) against Cutibacterium acnes ( C. acnes ) 6919 via targeting the fatty acid compositions and membrane properties. After exposure to S AB , C. acnes cells increased the cell surface hydrophobicity and reduced the cell membrane fluidity by changing the composition of membrane fatty acids. In the fatty acid compositions, the content of two main fatty acids 12-methyl-tetradecanoic acid (isoC15:0) and octadecanoic acid (C18:0) reduced and improved respectively with the addition of S AB , and fatty acid biosynthesis-related genes were significantly down-regulated ( p < 0.05). Further, molecular docking demonstrated that S AB interacted with FabD, which is an essential enzyme for bacterial type II fatty acid synthesis, via hydrogen bonds and hydrophobic interactions. In the above results, the contribution of S A to S AB was greater than that of S B . In summary, the results revealed that S AB changed the fatty acid compositions of C. acnes , further disrupting the cell membrane properties, and S A played a major role, suggesting that S AB could be a natural antiacne additive against C. acnes -associated infections.