Evidence of Emergent Silver-Resistance in Clinical Bacteria: A Major Implication for Wound Care and the use of Silver-Dressings
AbstractConcerns of emergent widespread silver resistance in clinical bacteria have been raised due to the increased utilization of inorganic silver in wound dressings. Although the molecular basis for silver-resistance has been previously characterized, to date, phenotypic expression of these genes has not been observed in clinical settings. Here we identified the first strains of clinical bacteria expressing silver-resistance at a level that could significantly impact wound care and the use of silver-dressings. After IRB approval, preliminary screening of 859 isolates identified 67 samples potentially harboring silver-resistant genes. Colony PCR confirmed 31 isolates had at least 1 silver-resistant gene. Next, we investigated whether the bacteria possessing silver-resistant genes expressed this trait phenotypically. Despite carrying silver-resistant genes, minimal inhibitory concentration (MIC) testing revealed that most of the bacteria displayed little or no increase in resistance to ionic silver (200 - 300μM Ag+). However, 2 isolates (Klebsiella pneumonia and Enterobacter cloacae) were capable of luxuriant growth at exceedingly high silver concentrations with MIC values reaching 5,500μM Ag+. An examination of the extracellular DNA of these two strains revealed small cryptic plasmids roughly sized 1.5, 2, and 2.5kb which were not present in the other bacteria with lower MIC values. We hypothesize these unanticipated DNA products are potential promoters for phenotypic expression of silver-resistance. Scanning Electron Microscopy images revealed the presence of silver nanoparticles embedded in the extracellular polymeric substance of both isolates. This finding suggested the isolates may neutralize ionic silver via reduction to elemental silver. Additional antimicrobial testing revealed these isolates to be at least 1,000 times more resistant to many commercially-available silver dressings when compared to control bacteria. Taken together, these findings provide the first evidence of emergent silver-resistance in clinical bacteria. The development of acute silver-resistance would have significant consequences on wound care and patient outcomes.
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