Silver(I), Mercury(II), Cadmium(II), and Zinc(II) Target Exposed Enzymic Iron-Sulfur Clusters when They Toxify Escherichia coli
Open Access
- 15 May 2012
- journal article
- Published by American Society for Microbiology in Applied and Environmental Microbiology
- Vol. 78 (10), 3614-3621
- https://doi.org/10.1128/aem.07368-11
Abstract
The toxicity of soft metals is of broad interest to microbiologists, both because such metals influence the community structures in natural environments and because several metals are used as antimicrobial agents. Their potency roughly parallels their thiophilicity, suggesting that their primary biological targets are likely to be enzymes that contain key sulfhydryl moieties. A recent study determined that copper poisons Escherichia coli in part by attacking the exposed [4Fe-4S] clusters of dehydratases. The present investigation sought to test whether other soft metals also target these enzymes. In vitro experiments revealed that low-micromolar concentrations of Ag(I) and Hg(II) directly inactivated purified fumarase A, a member of the dehydratase family. The enzyme was also poisoned by higher levels of Cd(II) and Zn(II), but it was unaffected by even millimolar concentrations of Mn(II), Co(II), Ni(II), and Pb(II). Electron paramagnetic resonance analysis and measurements of released iron confirmed that damage was associated with destruction of the [4Fe-4S] cluster, and indeed, the reconstruction of the cluster fully restored activity. Growth studies were then performed to test whether dehydratase damage might underlie toxicity in vivo. Barely toxic doses of Ag(I), Hg(II), Cd(II), and Zn(II) inactivated all tested members of the [4Fe-4S] dehydratase family. Again, activity was recovered when the clusters were rebuilt. The metals did not diminish the activities of other sampled enzymes, including NADH dehydrogenase I, an iron-sulfur protein whose clusters are shielded by polypeptide. Thus, the data indicate that dehydratases are damaged by the concentrations of metals that initiate bacteriostasis.Keywords
This publication has 47 references indexed in Scilit:
- Fructose‐1,6‐bisphosphate aldolase (class II) is the primary site of nickel toxicity in Escherichia coliMolecular Microbiology, 2011
- Role of reactive oxygen species in the antibacterial mechanism of silver nanoparticles on Escherichia coli O157:H7BioMetals, 2011
- Advances in metal-induced oxidative stress and human diseaseToxicology, 2011
- Metallic Copper as an Antimicrobial SurfaceApplied and Environmental Microbiology, 2011
- Hydrogen peroxide inactivates the Escherichia coli Isc iron‐sulphur assembly system, and OxyR induces the Suf system to compensateMolecular Microbiology, 2010
- The Right to Choose: Multiple Pathways for Activating Copper,Zinc Superoxide DismutaseJournal of Biological Chemistry, 2009
- The iron-sulfur clusters of dehydratases are primary intracellular targets of copper toxicityProceedings of the National Academy of Sciences, 2009
- Silver nanoparticles as a new generation of antimicrobialsBiotechnology Advances, 2009
- Elements and EvolutionScience, 2008
- Reexamination of Lead(II) Coordination Preferences in Sulfur-Rich Sites: Implications for a Critical Mechanism of Lead PoisoningJournal of the American Chemical Society, 2005