Towards resolution of antibacterial mechanisms in metal and metal oxide nanomaterials: a meta-analysis of the influence of study design on mechanistic conclusions

Abstract

While the antibacterial potency of metal and metal oxide engineered nanomaterials (MMO ENMs) has been well-established in the literature, the underlying mechanisms of antibacterial activity are regarded by many as uncertain, despite a considerable volume of publications on this subject. In order to illuminate sources of perceived uncertainty and disagreement, 318 articles pertaining to the mechanism of antimicrobial activity of Ag, Cu, CuO, TiO₂ and ZnO ENMs were analyzed. The 318 studies all aimed to assess one or more of eight mechanistic questions, and both positive (i.e. affirmative) and negative conclusions were reported for each mechanistic question for each of the five core compositions. Differences in study design, including the exposure conditions and experimental methods used, were found to statistically significantly correlate with differences in reported mechanistic conclusions. Further analysis of studies which investigated two or more mechanisms revealed how assumptions about which mechanisms predominate for a given core composition may influence study design and, in turn, conclusions. Finally, 181 distinct experimental methods were identified, many of which are relatively untested and have not been evaluated in the published literature, while many frequently-used methods were found to have limitations that may obscure interpretation and mechanistic insight.