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Methicillin-resistant  Staphylococcus aureus  (MRSA) isolates are often resistant to multiple antibiotics and pose a major health burden due to limited treatment options. The novel AGXX® surface coating exerts strong antimicrobial activity and successfully kills multi-resistant pathogens, including MRSA. The mode of action of AGXX® particles involves the generation of reactive oxygen species (ROS), which induce an oxidative and metal stress response, increased protein thiol-oxidations, protein aggregations, and an oxidized bacillithiol (BSH) redox state in  S. aureus . In this work, we report that the AGXX® particle size determines the effective dose and time-course of  S. aureus  USA300JE2 killing. We found that the two charges AGXX®373 and AGXX®383 differ strongly in their effective concentrations and times required for microbial killing. While 20–40 μg/ml AGXX®373 of the smaller particle size of 1.5–2.5 μm resulted in >99.9% killing after 2 h, much higher amounts of 60–80 μg/ml AGXX®383 of the larger particle size of >3.2 μm led to a >99% killing of  S. aureus  USA300JE2 within 3 h. Smaller AGXX® particles have a higher surface/volume ratio and therefore higher antimicrobial activity to kill at lower concentrations in a shorter time period compared to the larger particles. Thus, in future preparations of AGXX® particles, the size of the particles should be kept at a minimum for maximal antimicrobial activity.

The Antimicrobial Activity of the AGXX® Surface Coating Requires a Small Particle Size to Efficiently Kill Staphylococcus aureus