A Gateway to Antibiotic Resistance: Heavy Metals

By: Alexandra Ortiz

Heavy Metal Antibiotic-Resistant Superbugs. Schematic of the observed mechanisms in heavy metal stimulated transfer of antibiotic resistance. Sub-lethal concentrations of Copper (Cu), Silver (Ag), Chromium (Cr), and Zinc (Zn) were found to stimulate the transfer of antibiotic resistance genes between a donor E.coli and recipient E.coli strain (1) by the production of unstable oxygen molecules (2) and increase in membrane permeability (3). Mobile genetic elements such as plasmids can be transferred between bacteria when exposed to heavy metals at sub-lethal concentrations. (Figure Source: Ortiz, 2019).  

Despite the rise of antibiotic resistance being attributed to the overuse and misuse of antibiotics, scientists are discovering that chemicals other than antibiotics, such as heavy metals, can stimulate antibiotic resistance. Although naturally present in the environment, anthropogenic activities accelerate the release and accumulation of heavy metals into the environment. Zhang and colleagues found that heavy metals such as copper, silver, chromium, and zinc below lethal levels can promote the exchange of antibiotic resistance genes (ARGs) between two E. coli strains. Different mechanisms such as the production of unstable oxygen molecules, increased cell membrane permeability, and altered expression of transfer relevant genes were investigated to understand how heavy metals drive bacteria to become antibiotic-resistant. It was observed that transfer of ARGs increased as the concentration of metals increased (1). Furthermore, levels of unstable oxygen molecules increased significantly as a result of elevated metal ion concentration exposure (2). They also determined an upsurge in membrane permeability as a result of a loss of membrane integrity. It was found that certain sub-lethal concentrations of heavy metals upregulated the expression of these protein channels, resulting in a more permeable membrane that can readily uptake ARGs (3). With the rise of antibiotic-resistant bacterial infections rising, remediation strategies should be assessed to prevent heavy metal stimulated uptake of ARGs by bacteria.

Original Article: 

Zhang, Y., Gu, A.G., Cen, T., Li, X., He, M., Li, D., and J. Chen. (2018). Sub-inhibitory concentrations of heavy metals facilitate the horizontal transfer of plasmid-mediated antibiotic resistance genes in water environment. Environmental Pollution. 237:74-82.