Cho Hyejin, Naskar Atanu, Lee Sohee, Kim Semi, Kim Kwang-Sun
Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Busan 46241, Korea.
Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Korea.
Pharmaceutics. 2021 Feb 11;13(2):250. doi: 10.3390/pharmaceutics13020250.
Resistance to polymyxins when treating multidrug-resistant (MDR) Gram-negative bacterial infections limit therapeutic options. Here, we report the synthesis of a nickel (Ni) doped Zinc oxide (NZO) combined with black phosphorus (BP) (NZB) nanocomposite and its synergistic action with polymyxin B (PolB) against polymyxin-resistant harboring mobilized colistin resistance () gene. NZB and PolB combination therapy expressed a specific and strong synergy against Mcr-1 expressing cells. The underlying mechanism of the synergy is the charge neutralization of the cell surface by NZB, resulting in a more feasible incorporation of PolB to . The synergistic concentration of NZB with PolB was proved biocompatible. Thus, the NZB is the first biocompatible nano-adjuvant to polymyxins against polymyxin-resistant cells, recognizing the physical status of bacteria instead of known adjuvants targeting cellular gene products. Therefore, NZB has the potential to revive polymyxins as leading last-resort antibiotics to combat polymyxin-resistant Gram-negative bacterial infections.
在治疗多重耐药（MDR）革兰氏阴性菌感染时，对多粘菌素的耐药性限制了治疗选择。在此，我们报告了一种镍（Ni）掺杂的氧化锌（NZO）与黑磷（BP）结合的（NZB）纳米复合材料的合成及其与多粘菌素B（PolB）对携带可移动粘菌素耐药性（MCR）基因的耐多粘菌素菌的协同作用。NZB和PolB联合疗法对表达MCR-1的细胞表现出特异性且强大的协同作用。协同作用的潜在机制是NZB对细胞表面的电荷中和，导致PolB更易于结合到细胞上。NZB与PolB的协同浓度被证明具有生物相容性。因此，NZB是第一种对耐多粘菌素细胞具有生物相容性的多粘菌素纳米佐剂，它识别细菌的物理状态，而不是针对细胞基因产物的已知佐剂。因此，NZB有潜力使多粘菌素重振为对抗耐多粘菌素革兰氏阴性菌感染的主要最后手段抗生素。
