Experimental Evolution of Metal Resistance in Bacteria

There has been an increased usage of metallic antimicrobial materials to control pathogenic and multi-drug resistant bacteria, yet there is a corresponding need to know if this usage may lead to genetic adaptations that produce even more dangerous bacterial strains. In this paper we examine important recent results from the literature as well as report results from a series of our own studies. In that work, we utilized experimental evolution to produce strains of Escherichia coli K-12 MG1655 resistant to silver (Ag+), excess copper (Cu2+), excess iron (II, III), and the iron analog gallium (Ga3+). Silver and gallium are toxic to bacteria, whereas iron and copper are essential micronutrients that can be toxic in excess amounts. In all cases, the evolution of metal resistance was rapid and resulted in pleiotropic effects that included resistance to other metals as well as traditional antibiotics. Genomic analysis identified mutations in several genes associated with metal resistance, falling in several broad classes: genes that prevent entry of metal into the cell, genes involved in the energy-dependent efflux of metal out of the cell, genes associated with ROS-induced membrane damage, and genes associated with transcription.