Proteomic Identification of the Cus System as a Major Determinant of Constitutive Escherichia coli Silver Resistance of Chromosomal Origin

Although silver is one of the most potent and rapidly acting toxic metals to bacteria, silver-resistant bacteria do exist with low incidence. A proteomic approach was employed to identify the silver resistance determinants of a silver-resistant Escherichia coli strain isolated from stepwise selection against increasing concentrations of silver (Li et al. J. Bacteriol 1997, 179, 6127-32). Two-dimensional gel electrophoresis and mass spectrometry analysis revealed that members of the CusCFBA copper/silver chemiosmotic efflux system were highly expressed in the silver-resistant strain but undetectable in the parental silver-sensitive strain. Disruption of the cus locus of the silver-resistant strain resulted in a decrease of the minimum inhibitory concentration of Ag (+) from more than 1 mM to 12 microM. These results suggest that the chromosomally encoded Cus system, which naturally controls the periplasmic copper concentrations, is selectable to confer a constitutive silver resistance phenotype.