Department of Biomedical Engineering, Shenzhen Bay Laboratory, Southern University of Science and Technology, No. 1088, Xueyuan Road, Xili, Nanshan District, Shenzhen, Guangdong 518055, P. R. China.
Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, Guangdong 518060, P. R. China.
Nano Lett. 2021 Mar 10;21(5):1992-2000. doi: 10.1021/acs.nanolett.0c04451. Epub 2021 Feb 22.
One major frustration in developing antibiotics is that bacteria can quickly develop resistance that would require an entirely new cycle of research and clinical testing to overcome. Although plenty of bactericidal nanomaterials have been developed against increasingly severe superbugs, few reports have studied the resistance to these nanomaterials. Herein, we show that antibacterial 4,6-diamino-2-pyrimidine thiol (DAPT)-capped gold nanoparticles (AuDAPTs) can induce a 16-fold increased minimum inhibitory concentration (MIC) of only after very long term exposure (183 days), without developing cross-resistance to commercialized antibiotics. Strikingly, we recovered the bactericidal activities of AuDAPTs to the resistant strain by tuning the sizes of AuDAPTs without employing new chemicals. Such slow, easy-to-handle resistance induced by AuDAPTs is unprecedented compared to traditional antibiotics or other nanomaterials. In addition to the novel antibacterial activities and biocompatibilities, our approach will accelerate the development of gold nanomaterial-based therapeutics against multi-drug-resistant (MDR) bacterial infections.
在开发抗生素时，一个主要的挫折是细菌可以迅速产生耐药性，这将需要一个全新的研究和临床测试周期来克服。尽管已经开发出了大量针对日益严重的超级细菌的杀菌纳米材料，但很少有研究报道过这些纳米材料的耐药性。在此，我们展示了抗菌 4,6-二氨基-2-嘧啶硫醇（DAPT）封端的金纳米粒子（AuDAPTs）在非常长的暴露时间（183 天）后仅会导致最低抑菌浓度（MIC）增加 16 倍，而不会对商业化抗生素产生交叉耐药性。引人注目的是，我们通过调整 AuDAPTs 的尺寸恢复了对耐药菌株的杀菌活性，而无需使用新的化学物质。与传统抗生素或其他纳米材料相比，AuDAPTs 诱导的这种缓慢、易于处理的耐药性是前所未有的。除了新颖的抗菌活性和生物相容性外，我们的方法还将加速基于金纳米材料的治疗剂的开发，以对抗多药耐药（MDR）细菌感染。
