Copper Stress Response of Antibiotic‐Resistant and Copper‐Tolerant Enterococcus faecium and the Antibacterial Efficacy of Functionalized Copper Surfaces

Abstract The widespread use of antibiotics worldwide has led to an increase in multi‐resistant pathogens, including vancomycin‐resistant enterococci (VRE). To prevent the spread of multi‐resistant pathogens, antimicrobial surfaces have become more widely used. Various metals and surface topographies are researched to optimize their bactericidal effect. Copper surfaces have proven cost‐effective, easy to implement, and safe. However, concurrent metal resistance in Enterococcus faecium , leads to strains highly resistant to both vancomycin and copper. The efficacy of copper coatings are evaluated, and copper and brass surfaces are functionalized with Direct Laser Interference Patterning (DLIP) and determined the release of copper and zinc ions during cell‐surface. Additionally, the copper stress response of five E. faecium isolates is characterized by scanning and transmission electron microscopy, determination of the minimal inhibitory concentration (MIC) on copper‐infused media, and whole‐genome sequencing. The copper stress responses of the isolates differed due to their different copper resistance genes. In particular, it is shown that prior exposure to vancomycin enhanced copper tolerance in E. faecium . Furthermore, the copper‐tolerant isolate is the only one to survive direct contact with the functionalized copper surface. These results highlight the importance of investigating antimicrobial and functionalized surfaces against hospital pathogens and co‐resistance against metal and antibiotics.