'Superbug' bacteria producing NDM-1 enzyme causing wide public concern were first detected in a patient who visited India in 2008. It's an effective approach to combining beta-lactam antibiotics with NDM-1 inhibitor for treating NDM-1 producing strain infection. In our research, we designed ten oligopeptides, tested IC50 values against NDM-1 enzyme, determined the MIC values of synergistic antibacterial effect and explored the binding model. We found that the oligopeptides 2 (Cys-Phe) and 5 (Cys-Asp) respectively presented IC50 values of 113 mu M and 68 mu M and also displayed favorable synergistic effects of the inhibitors in combination with ertapenem against genetic engineering-host E. coli BL21 (DE3)/pET30aNDM-1 and a clinical isolate of P. aeruginosa with bla(NDM-1). Flexible docking and partial charge study suggested the interaction between oligopeptide and NDM-1. Three types of action effects, hydrogen bond, electrostatic effect and pi-pi interaction, contributed to the inhibitory activities.
基金:
Open Research Fund Program of State Key Laboratory of Virology of China [2016KF002]; National Natural Science Foundation of China [31100253, 81672079]