The membrane-targeting mechanism of host defense peptides inspiring the design of polypeptide-conjugated gold nanoparticles exhibiting effective antibacterial activity against methicillin-resistant <i>Staphylococcus aureus</i>
Weiwei Zhang, Yueming Wu, Longqiang Liu, Ximian Xiao, Zihao Cong, Ning Shao, Zhongqian Qiao, Kang Chen, Shiqi Liu, Haodong Zhang, Zhemin Ji, Xiaoyan Shao, Yidong Dai, Hongyan He, Jiang Xia, Jian Fei, Runhui Liu
Abstract
Multidrug-resistant bacterial infections are a grand challenge to global medical and health systems. Therefore, it is urgent to develop versatile antibacterial strategies that can combat bacterial resistance without displaying toxicity. Here, we synthesize antibacterial polypeptide-conjugated gold nanoparticles that exhibit potent antibacterial activities against clinically isolated multiple drug resistance Gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus, and excellent in vitro and in vivo biocompatibility. The antibacterial mechanism study indicates that over-production of reactive oxygen species results in the killing of bacteria. The overall antibacterial performance of these polypeptide-conjugated gold nanoparticles and the convenient synthesis of these polypeptides via lithium hexamethyldisilazide-initiated fast ring-opening polymerization on α-amino acid N-carboxyanhydride imply the potential application of this strategy in treating bacterial infections.