Synergistic antibacterial combination of Sapindoside A and B changes the fatty acid compositions and membrane properties of Cutibacterium acnes

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 (SAB) against Cutibacterium acnes (C. acnes) 6919 via targeting the fatty acid compositions and membrane properties. After exposure to SAB, 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 SAB, and fatty acid biosynthesis-related genes were significantly down-regulated (p < 0.05). Further, molecular docking demonstrated that SAB 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 SA to SAB was greater than that of SB. In summary, the results revealed that SAB changed the fatty acid compositions of C. acnes, further disrupting the cell membrane properties, and SA played a major role, suggesting that SAB could be a natural antiacne additive against C. acnes-associated infections.