High Frequency of Silver Resistance in Invasive Isolates Belonging to Genera Enterobacter and Klebsiella. Silver resistance in Gram-negative bacteria

Objectives: To investigate the frequency of genetic and phenotypic resistance to silver in invasive Enterobacteriaceae isolates, and to explore the genetic background to silver-resistance selected in vivo and in vitro. Methods: In order to study the presence of genes encoding silver resistance (silE, silP, silS) over time, 752 blood isolates collected during the years 1990-2010 were investigated with PCR. Age, gender and ward of patients were registered, and the susceptibility to antibiotics and silver nitrate was tested. Clonality and single nucleotide polymorphism were assessed with rep-PCR, multilocus sequence typing, and whole-genome sequencing. Results: Genes encoding silver resistance were detected most frequently in Enterobacter spp. (48%), followed by Klebsiella spp. (41%). Thirteen percent of the Enterobacter isolates and 3% of the Klebsiella isolates were phenotypically resistant to silver nitrate. Presence of sil genes was observed in international high-risk clones. Sequences of the sil operon indicated that mutational events in certain regions of the silS gene caused the phenotypic resistance. Conclusions: Despite a restricted consumption of silver-based products in the Swedish health care, silver resistance genes are widely represented in clinical isolates of the genera Enterobacter and Klebsiella. To avoid further selection and spread to other healthcare-related pathogens, silver resistance need to be monitored.