Bacterial colonization of implantable biomaterials is an ever-pervasive threat that causes devastating infections, yet continues to elude resolution. In the present study, we report how a rationally designed antibacterial surface containing sharp nanospikes can enhance the susceptibility of pathogenic bacteria to antibiotics used in prophylactic procedures. We show that Staphylococcus aureus, once adhered to a titanium surface, changes its cell-surface charge to increase its tolerance to vancomycin. However, if the Ti surface is modified to bear sharp nanospikes, the activity of vancomycin is rejuvenated, leading to increased bacterial cell death through synergistic activity. Analysis of differential gene expression provided evidence of a set of genes involved with the modification of cell surface charge. Synchrotron-sourced attenuated Fourier-transform infrared microspectroscopy (ATR-FTIR), together with multivariate analysis, was utilized to further elucidate the biochemical changes of S. aureus adhered to nanospikes. By inhibiting the ability of the pathogen to reduce its net negative charge, the nanoengineered surface renders S. aureus more susceptible to positively charged antimicrobials such as vancomycin. This finding highlights the opportunity to enhance the potency of prophylactic antibiotic treatments during implant placement surgery by employing devices having surfaces modified with spike-like nanostructures.

可植入生物材料的细菌定植是一种普遍存在的威胁，会导致毁灭性感染，但仍然无法得到解决。在本研究中，我们报告了合理设计的含有尖锐纳米尖峰的抗菌表面如何增强病原菌对预防过程中使用的抗生素的敏感性。我们发现，金黄色葡萄球菌一旦粘附到钛表面，就会改变其细胞表面电荷，从而增加其对万古霉素的耐受性。然而，如果钛表面被修饰为带有尖锐的纳米尖峰，万古霉素的活性就会恢复，通过协同活性导致细菌细胞死亡增加。差异基因表达的分析提供了一组与细胞表面电荷修饰有关的基因的证据。利用同步加速器来源的衰减傅里叶变换红外显微光谱 (ATR-FTIR) 以及多变量分析，进一步阐明了粘附在纳米刺上的金黄色葡萄球菌的生化变化。通过抑制病原体减少其净负电荷的能力，纳米工程表面使金黄色葡萄球菌更容易受到万古霉素等带正电荷的抗菌剂的影响。这一发现凸显了通过使用表面经过尖峰状纳米结构修饰的装置来增强植入手术期间预防性抗生素治疗效力的机会。