Interaction of houttuyfonate homologues with the cell membrane of gram-positive and gram-negative bacteria

The antibacterial activity test indicated that gram-positive (G+) bacteria, Staphylococcus aureus and Bacillus subtilis were more sensitive to houttuyfonate homologues (HOU-Cn) than gram-negative (G−) bacteria, Escherichia coli and Pseudomonas aeruginosa, and the sensitivity increased with the elongation of hydrocarbon chain of HOU-Cn. Accordingly, the effects of HOU-Cn on the membrane permeability, the lipid fluidity and the protein conformation of G+- and G−-bacteria were investigated to elucidate the antibacterial mechanism of HOU-Cn. The results showed that no significant change in membrane permeability and fluidity of S. aureus and E. coli was observed, suggesting that the inhibition of HOU-Cn to bacteria was not caused by the interaction of HOU-Cn with membrane lipids of the bacteria. The fluorescence experiments indicated that HOU-Cn directly bound to membrane proteins of G+-bacteria by hydrophobic interaction, and exerted a stronger antibacterial activity. But HOU-Cn firstly interacted with proteins at the cell wall of G−-bacteria, and correspondingly its effective concentration binding to the proteins of plasma membrane was greatly decreased. Therefore it exerted a weaker inhibition to G−-bacteria.