A spontaneous solid-state NO donor to fight antibiotic resistant bacteria

This study substantiates the chemical origin of a free-radical-driven antibacterial effect at the surface of biomedical silicon nitride (Si₃N₄) in comparison with the long-known effect of oxygen reduction by oxidized TiO₂ at the surface of biomedical titanium alloys. Similar to the antibacterial effect exerted by reactive oxygen species (ROS; i.e., superoxide anions, hydroxyl radicals, singlet oxygen, and hydrogen peroxide) from TiO₂, reactive nitrogen species (RNS), such as nitrous oxide (N₂O), nitric oxide (NO), and peroxynitrite (^?OONO) in Si₃N₄, severely affect bacterial metabolism and lead to their lysis. However, in vitro experiment with gram-positive Staphylococcus epidermidis (S. epidermidis, henceforth) revealed that ROS and RNS promoted different mechanisms of lysis. Fluorescence microscopy of NO radicals and in situ time-lapse Raman spectroscopy revealed different metabolic responses of living bacteria in contact with different substrates. After 48 h, the DNA of bacteria showed complete destruction on Si₃N₄, while carbohydrates of the peptidoglycan membrane induced bacterial degradation on Ti-alloy substrates. Different spectroscopic fingerprints for bacterial lysis documented the distinct effects of RNS and ROS. Spontaneously activated in aqueous environment, the RNS chemistry of Si₃N₄ proved much more effective in counteracting bacterial proliferation as compared to ROS formed on TiO₂, which requires external energy (photocatalytic activation) to enhance effectiveness. Independent of surface topography, the antibacterial effect observed on Si₃N₄ substrates is due to its unique kinetics ultimately producing NO and represents a new intriguing avenue to fight bacterial resistance to conventional antibiotics.