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

Abstract

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.

A Novel Silver-Containing Antimicrobial potentiates aminoglycoside activity againstPseudomonas aeruginosa

“…AGXX's potentiating effect was not limited to select aminoglycosides but applied to all members tested including gentamicin, streptomycin, amikacin, and tobramycin (FIG 2). Additional support for AGXX's stimulating effect on aminoglycoside activity was provided by its ability to re-sensitize a kanamycin resistant between silver (Ag) and ruthenium (Ru x+1 ) (15,16). While the location of AGXX-mediated ROS production was not the focus of his study, we propose that ROS is mainly generated in the extracellular part before the compounds penetrate the cell.…”

“…Based on our findings, we propose the following model for the synergy between AGXX and aminoglycoside antibiotics ( FIG 9 ): The antimicrobial action of AGXX is mediated by superoxide (O 2 - ) and hydrogen peroxide (H 2 O 2 ), which are generated in a redox cycle between silver (Ag) and ruthenium (Ru x+1 ) (15, 16). While the location of AGXX-mediated ROS production was not the focus of his study, we propose that ROS is mainly generated in the extracellular part before the compounds penetrate the cell.…”

“…; https://doi.org/10.1101/2023.03. 15.532855 doi: bioRxiv preprint dehydratase enzymes, and replace metal-containing cofactors, thus affecting a wide range of cytoplasmic and membrane proteins (9,10). More recently, silver derivates have received increased attention in medical applications, e.g.…”

“…; https://doi.org/10.1101/2023.03. 15.532855 doi: bioRxiv preprint bactericidal mode of action of aminoglycoside, fluoroquinolone and beta-lactam antibiotics have proposed increased endogenous ROS stress as an additional mechanism for bacterial killing (5,20,21). Notably, activation of the bacterial envelope stress response, hyperactivation of the electron transport chain, and damage of iron sulfur clusters have been shown to contribute to an increase in endogenous ROS level (5).…”

Microbiota shaping and bioburden monitoring of indoor antimicrobial surfaces

“…Depending on the antimicrobial material, environmental conditions, and microorganisms involved, the inactivation time of microbes ranges from minutes to hours after contamination (Querido et al, 2019;Bäumler et al, 2021). Antimicrobial efficiency is also dependent on the concentration and particle size of antimicrobial products (Linzner and Antelmann, 2021).…”