Grup de Biotecnologia Molecular i Industrial, Department of Chemical Engineering, Universitat Politècnica de Catalunya, Rambla Sant Nebridi 22, 08222 Terrassa, Spain.
Int J Mol Sci. 2022 Jul 11;23(14):7632. doi: 10.3390/ijms23147632.
The emergence of antibiotic resistant bacteria coupled with the shortage of efficient antibacterials is one of the most serious unresolved problems for modern medicine. In this study, the nano-hybridization of the clinically relevant antibiotic, gentamicin, with the bacterial pro-pathological cell-to-cell communication-quenching enzyme, acylase, is innovatively employed to increase its antimicrobial efficiency against planktonic cells and biofilms. The sonochemically generated hybrid gentamicin/acylase nano-spheres (GeN_AC NSs) showed a 16-fold improved bactericidal activity when compared with the antibiotic in bulk form, due to the enhanced physical interaction and disruption of the cell membrane. The nano-hybrids attenuated 97 ± 1.8% of the quorum sensing-regulated virulence factors' production and inhibited the bacterium biofilm formation in an eight-fold lower concentration than the stand-alone gentamicin NSs. The sensitivity to GeN_AC NSs was also confirmed in a real time assay monitoring the bacterial cells elimination, using a quartz crystal microbalance with dissipation. In protein-enriched conditions mimicking the in vivo application, these hybrid nano-antibacterials maintained their antibacterial and antibiofilm effectiveness at concentrations innocuous to human cells. Therefore, the novel GeN_AC NSs with complementary modes of action show potential for the treatment of biofilm infections at a reduced antibiotic dosage.
抗生素耐药菌的出现加上高效抗菌药物的短缺，是现代医学尚未解决的最严重问题之一。在本研究中，创新性地将临床上相关的抗生素庆大霉素与细菌前病理细胞间通讯抑制酶——酰化酶进行纳米杂交，以提高其对浮游细胞和生物膜的抗菌效率。与散装抗生素相比，超声化学生成的杂交庆大霉素/酰化酶纳米球（GeN_AC NSs）表现出 16 倍的杀菌活性增强，这是由于物理相互作用增强和细胞膜破裂所致。纳米杂化物降低了 97±1.8%的群体感应调节毒力因子的产生，并以比独立的庆大霉素 NSs 低 8 倍的浓度抑制了细菌生物膜的形成。使用石英晶体微天平（QCM-D）监测细菌细胞消除的实时分析，也证实了对 GeN_AC NSs 的敏感性。在模拟体内应用的富含蛋白质的条件下，这些新型的复合纳米抗菌药物在对人体细胞无害的浓度下仍保持其抗菌和抗生物膜的有效性。因此，具有互补作用模式的新型 GeN_AC NSs 具有减少抗生素用量治疗生物膜感染的潜力。
