Electrostatic charge at the biomaterial-pathogen interface influences antibiotic efficacy

Implant-associated infections (IAI) are a considerable burden for healthcare systems globally. While novel anti-infective biomaterials are being pursued, prophylactic antibiotic treatment remains the most important intervention for mitigating IAI. The antibiotic tolerance of bacteria has been widely studied, but until recently, the contributions of biomaterial-pathogen interactions have been overlooked. In the present study, we investigate how material electrostatic charge influences the physiological state of the most clinically challenging pathogen-Staphylococcus aureus, and the implications on its antibiotic tolerance. We utilized a combination of techniques, including quantitative gene expression and synchrotron-sourced attenuated total reflectance Fourier-transform microspectroscopy, to characterize this phenomenon - elucidating how surface attachment to differently charged substrates drives the pathogen to modify its phenotype. Subsequently, we found a direct relationship between the activity of oppositely charged antibiotics (vancomycin and cefazolin) and the biomaterial-pathogen interface, which we determined to be governed by material electrostatic properties. The findings of the present study have the potential to inform the development of enhanced procedures of antibiotic prophylaxis by instructing personalized biomaterial-antibiotic pairing strategies. These new insights hold promise to contribute to reducing the rate of IAI by enabling clinicians and surgeons to maximize the efficacy of prophylactic antibiotic treatments during implant placement procedures.