Shen Bingzheng, Zhu Chengliang, Gao Xiang, Liu Gang, Song Jinchun, Yu Yan
Department of Pharmacy, Renmin Hospital, Wuhan University, Wuhan, China.
State Key Laboratory of Virology, Wuhan University, Wuhan, China.
PLoS One. 2017 May 23;12(5):e0177293. doi: 10.1371/journal.pone.0177293. eCollection 2017.
'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 β-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 μM and 68 μM and also displayed favorable synergistic effects of the inhibitors in combination with ertapenem against genetic engineering-host E. coli BL21 (DE3)/pET30a-NDM-1 and a clinical isolate of P. aeruginosa with blaNDM-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 π-π interaction, contributed to the inhibitory activities.
产生NDM - 1酶的“超级细菌”引发了广泛的公众关注，这种细菌于2008年在一名前往印度的患者身上首次被检测到。将β - 内酰胺类抗生素与NDM - 1抑制剂联合使用是治疗产NDM - 1菌株感染的有效方法。在我们的研究中，我们设计了十种寡肽，测试了它们对NDM - 1酶的IC50值，确定了协同抗菌作用的MIC值，并探索了结合模式。我们发现寡肽2（半胱氨酸 - 苯丙氨酸）和5（半胱氨酸 - 天冬氨酸）的IC50值分别为113μM和68μM，并且在与厄他培南联合使用时，对基因工程宿主大肠杆菌BL21（DE3）/pET30a - NDM - 1和携带blaNDM - 1的铜绿假单胞菌临床分离株也显示出良好的协同作用。柔性对接和部分电荷研究表明了寡肽与NDM - 1之间的相互作用。氢键、静电作用和π - π相互作用这三种作用效应促成了抑制活性。
