Smart active antibiotic nanocarriers with protease surface functionality can overcome biofilms of resistant bacteria

Abstract

Treating bacterial infections with species demonstrating antibiotic resistance to the chosen antibiotic is often hindered due to the ability of certain bacteria to grow biofilms where they can effectively hide and resist the antibiotic action. We report an innovative solution for overcoming both antibiotic resistance and biofilm formation by designing active antibiotic nanocarriers with protease surface functionality. We show that this active nanocarrier of common antibiotics can efficiently degrade biofilms of resistant bacteria and bypass their defences. The cationic protease coating, whilst allowing electrostatic adhesion of the nanoparticle to the cell, simultaneously also degrades the biofilm and helps the active nanocarriers to reach the entrapped bacterial cells. We demonstrated this concept by encapsulating Penicillin G and Oxacillin into shellac nanoparticles, subsequently coated with a serine endo-peptidase protease, Alcalase 2.4 L FG. We show for the first time that these active nanocarriers can destroy biofilms of S. aureus resistant to Penicillin G and are significantly more effective in killing the bacterial cells within compared to an equivalent concentration of free antibiotic. The approach of concentrating the antibiotic by encapsulating it into a nanocarrier allows a localised delivery of the antibiotic to the anionic cell wall, facilitated by coating the NPs with a cationic protease. This approach allowed the antibiotic to restore its effectiveness against S. aureus, characterised as resistant to the same antibiotic as well as to cause a rapid degradation of the bacterial biofilm. This approach could be potentially used to revive old antibiotics which have already limited clinical use due to developed resistance.