Silica Nanoparticles Block Natural Genetic Transformation in Acinetobacter baylyi ADP1

The prolonged and widespread use of antibiotics has driven the emergence of resistance to many commonly employed drugs, posing a growing global challenge that requires urgent measures to curb its spread. Once resistance develops, horizontal gene transfer facilitates the exchange of genetic materials among various bacterial species, often preceding vertical transmission. Previous work to control horizontal gene transfer and specifically natural transformation within a population of bacteria approached the problem by addressing the bacterial mechanisms required for transformation. In this study, we investigated the possibility of controlling horizontal gene transfer by limiting access to or the availability of environmental DNA to the bacteria. In this study, we investigated the impact of five different sizes of silica nanoparticles (SiO₂NPs), 20, 80, 120, 200, and 500 nm, and three sizes of gold nanoparticles (AuNPs), 5, 20, and 200 nm, on the natural genetic transformation of Acinetobacter baylyi ADP1 (A. baylyi ADP1) using both circular and linear environmental DNA (pBTK501) carrying an ampicillin resistance cassette. Our findings reveal that SiO₂NPs ranging from 120 to 500 nm consistently inhibited transformation events in both M9 and LB media. SiO₂NPs effectively suppress the natural transformation of A. baylyi ADP1 in the presence of circular pBTK501 with a stronger effect on the linear pBTK501. The degree of inhibition was size-dependent, as the 500 nm SiO₂NPs exhibited the strongest effect. The inhibitory effect of SiO₂NPs was also found to be dose-dependent: increasing the pBTK501 concentration relative to the SiO₂NPs diminished the inhibition, while a higher SiO₂NP-to-pBTK501 ratio resulted in a stronger inhibition. Similarly, the 200 nm AuNPs also displayed a notable inhibitory effect on the natural transformation of A. baylyi ADP1. These results, taken together, appear to show the ability of nanoparticles to control natural transformations in A. baylyi ADP1. This size-dependent mechanism clearly defines a path to mitigate the spread of resistance evolution both at the hospital and community settings, which hitherto has not been given adequate consideration.