Contrasts and similarities in the transcriptomic response to antimicrobial coinage metals in Escherichia coli

ABSTRACT With the rise of resistance to last-resort antibiotics, metal-based antimicrobials have re-emerged as an alternative to prevent and manage infections. The group 11 metals (copper, silver, gold), historically known for their usage in coins, have demonstrated promising bactericidal activity. Despite their efficiency, we do not have a complete understanding of how bacteria are eradicated by metal ions and how they respond to metal-induced stress. Additionally, most studies in the field focus on the physiological response to acute toxicity, often overlooking longer exposure models. We used RNA-seq profiling to understand the Escherichia coli physiological response to sublethal inhibitory antimicrobial coinage metal stress after 10 hours of incubation. Gene expression patterns of the adaptive and intrinsic response elicited by each metal were identified, including increased essential metal uptake (Ag, Cu, Au), cysteine biosynthesis (Cu, Au), change of the metal ion oxidation state (Cu, Au), efflux of metal stressor (Cu), protein translation, and ribosome biogenesis (Au), and cell envelope stress response (Ag). We highlight the remarkable differences and similarities in the transcriptomic response profile of E. coli to these antimicrobial metal elements. IMPORTANCE Dogma existed in the past, stating that all antimicrobial metals kill bacteria the same way. Thus, the assumption was that bacteria respond the same way to metal toxicity. Nowadays, we understand better why some metal elements are more toxic than others, but questions remain in relation to how bacteria adapt to survive and thrive when challenged by different metal-based antimicrobials. Our study advances the field by characterizing the type of bacterial response needed to acclimate and grow in the presence of silver, copper, and gold—metallic elements known for their antimicrobial activity. Taking advantage of well-characterized Escherichia coli , we propose a model that summarizes our findings after comparing the shared and unique responses to each of these metals. This information enhances our understanding of bacterial tolerance to metal-based antimicrobials, which can lead to improved drug development strategies as society continues to search for alternatives against antibiotic-resistant pathogens.