Cryptic silver resistance is prevalent and readily activated in certain Gram-negative pathogens

Objectives: To assess the prevalence of cryptic silver (Ag+) resistance amongst clinical isolates of Gram-negative bacteria, and to examine how overt Ag+ resistance becomes activated in such strains. Methods: Established methods were used to determine the susceptibility of 444 recent clinical isolates to Ag+, and to evaluate the potential for overt Ag+ resistance to emerge from these isolates by spontaneous mutation. The genetic basis for Ag+ resistance was investigated using PCR amplification and DNA sequencing. Results: None of the isolates tested displayed overt Ag+ resistance. However, upon silver challenge, high-level Ag+ resistance (silver nitrate MIC >128 mg/L) was selected at high frequency (10¯⁷ to 10¯⁸) in ˜76% isolates of Enterobacter spp., ˜58% isolates of Klebsiella spp., and ˜0.7% isolates of E. coli. All strains in which Ag+ resistance could be selected harboured the sil operon, with resistance in each case apparently resulting from activation of this system as a consequence of a single missense mutation in silS. By contrast, Ag+ resistance could not be selected in isolates lacking sil, which included all tested representatives of Acinetobacter baumannii, Pseudomonas aeruginosa, Proteus spp and Citrobacter spp. Conclusions: Whilst overt Ag+ resistance in Gram-negative pathogens is uncommon, cryptic Ag+ resistance pertaining to the sil operon is prevalent and readily activated in particular genera (Enterobacter and Klebsiella).