title: Silver-resistant mutants of Escherichia coli display active efflux of Ag+ and are deficient in porins.
abstract: Silver-resistant mutants were selected by stepwise exposure of silver-susceptible clinical strains of Escherichia coli, two of which did not contain any plasmids, to either silver nitrate or silver sulfadiazine. These mutants showed complete cross-resistance to both compounds. They showed low-level cross-resistance to cephalosporins and HgCl2 but not to other heavy metals. The Ag-resistant mutants had decreased outer membrane (OM) permeability to cephalosporins, and all five resistant mutants tested were deficient in major porins, either OmpF or OmpF plus OmpC. However, the well-studied OmpF- and/or OmpC-deficient mutants of laboratory strains K-12 and B/r were not resistant to either silver compound. Resistant strains accumulated up to fourfold less (110m)AgNO3 than the parental strains. The treatment of cells with carbonyl cyanide m-chlorophenylhydrazone increased Ag accumulation in Ag-susceptible and -resistant strains, suggesting that even the wild-type Ag-susceptible strains had an endogenous Ag efflux activity, which occurred at higher levels in Ag-resistant mutants. The addition of glucose as an energy source to starved cells activated the efflux of Ag. The results suggest that active efflux, presumably coded by a chromosomal gene(s), may play a major role in silver resistance, which is likely to be enhanced synergistically by decreases in OM permeability.
authors.affiliation: Department of Microbiology, University of Saskatchewan, Saskatoon, Canada. 6x1@qlink.queensu.ca
authors.forename: X Z
authors.initials: XZ
authors.lastname: Li
authors.forename: H
authors.initials: H
authors.lastname: Nikaido
authors.forename: K E
authors.initials: KE
authors.lastname: Williams
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D002463:Cell Membrane Permeability; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D019216:Metals, Heavy / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009154:Mutation; D018272:Porins / Q000378:metabolism*; D012834:Silver / Q000378:metabolism* / Q000494:pharmacology*; D012835:Silver Nitrate / Q000494:pharmacology; D012837:Silver Sulfadiazine / Q000494:pharmacology; D014475:Uncoupling Agents / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D019216:Metals, Heavy; D018272:Porins; D014475:Uncoupling Agents; D012834:Silver; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D000255:Adenosine Triphosphate; D012835:Silver Nitrate; D012837:Silver Sulfadiazine