Inhibitory effect of soy saponins on the activity of β-lactamases, including New Delhi metallo-β-lactamase 1

Hitoshi Horie, Asuka Chiba, Shigeo Wada

β-Lactamase-producing bacteria encode enzymes that inactivate β-lactam antibiotics by catalyzing the hydrolysis of the β-lactam ring. Crude soy saponins were observed to have synergistic effects on the antimicrobial activity of β-lactam antibiotics against β-lactamase-producing Staphylococcus aureus strains. Furthermore, the activities of β-lactamases derived from Enterobacter cloacae, Escherichia coli, and S. aureus were decreased significantly in the presence of crude soy saponins. This inhibitory effect was also observed against the New Delhi metallo-β-lactamase 1 (NDM-1), an enzyme whose activity is not inhibited by the current β-lactamase inhibitors. The synergistic effect on the antimicrobial activity of β-lactam antibiotics by crude soy saponins was thought to result from the inhibition the β-lactamase activity. The components of crude soy saponins include several kinds of soyasaponins and soyasapogenols. It was revealed that soyasaponin V has the highest inhibitory activity against NDM-1. The combined use of soy saponins with β-lactam antibiotics is expected to serve as a new therapeutic modality, potentially enhancing the effectiveness of β-lactam antibiotics against infectious diseases caused by β-lactamase-producing bacteria, including those encoding NDM-1.