While traditional drug discovery continues to be an important platform for the search of new antibiotics, alternative approaches should also be pursued to complement these efforts. We herein designed a class of molecules that decorate bacterial cell surfaces with the goal of re-engaging components of the immune system towardEscherichia coliandPseudomonas aeruginosa. More specifically, conjugates were assembled using polymyxin B (an antibiotic that inherently attaches to the surface of Gram-negative pathogens) and antigenic epitopes that recruit antibodies found in human serum. We established that the spacer length played a significant role in hapten display within the bacterial cell surface, a result that was confirmed both experimentally and via molecular dynamics simulations. Most importantly, we demonstrated the specific killing of bacteria by our agent in the presence of human serum. By enlisting the immune system, these agents have the potential to pave the way for a potent antimicrobial modality.

中文翻译：

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革兰氏阴性病原菌的综合免疫治疗

尽管传统的药物发现仍然是寻找新抗生素的重要平台，但也应寻求替代方法来补充这些努力。我们在本文中设计了一类装饰细菌细胞表面的分子，目的是使免疫系统的成分重新结合大肠杆菌和铜绿假单胞菌。更具体地说，使用多粘菌素B（一种固有地附着于革兰氏阴性病原体表面的抗生素）和募集在人血清中发现的抗体的抗原表位组装缀合物。我们确定间隔长度在细菌细胞表面内的半抗原显示中起着重要作用，这一结果在实验和分子动力学模拟中均得到了证实。最重要的是，我们证明了在人血清存在下我们的药剂对细菌的特异性杀灭。通过招募免疫系统，这些药物有可能为有效的抗菌方法铺平道路。