Molecular insights into silver nanoparticle resistance in Acinetobacter baumannii and unique adaptations to ionic silver

Abstract This research provides molecular insights into the evolutionarily adapted defense mechanisms of a bacterial pathogen against the complex antimicrobial activity of silver nanoparticles at the transcriptional level. The Gram-negative, biofilm-forming bacterium Acinetobacter baumannii upregulated outer membrane proteins along with genes involved in membrane and capsule synthesis, suggestive of enhanced cell surface defense. An increase in surface-attached biofilm colonies in nanosilver-resistant A. baumannii (NAg R ) appeared to be associated with enhanced cell membrane integrity and a greater production of extracellular polymeric substances (EPS), the matrix that protects the resident colony. In response to reactive oxygen species (ROS), a recognized toxicity characteristic of the nanoparticle, NAg R upregulated its oxidative stress management system, specifically involving ROS scavenger enzymes and opportunistic metal efflux pumps. Majority of these modified defense mechanisms manifested in the resistant bacterium, while absent in the wild-type strain. This study also details the unique defenses of an ionic silver-tolerant A. baumannii (Ag T ) variant, which evolved from the same parental strain as NAg R . Despite similarities in cell surface and biofilm defense traits, the slower-to-kill tolerant strain exclusively upregulated multidrug efflux systems and respiratory chain enzymes, thought to maintain enhanced respiratory activity, a reported tolerance characteristic. While these findings would benefit from further validating experimental work, identification of these stable defense mechanisms can help better elucidate the complex nature of bacterial NAg adaptation phenomena.