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Unprecedented Silver Resistance in Clinically Isolated Enterobacteriaceae: Major Implications for Burn and Wound Management.

ABSTRACT: Increased utilization of inorganic silver as an adjunctive to many medical devices has raised concerns of emergent silver resistance in clinical bacteria. Although the molecular basis for silver resistance has been previously characterized, to date, significant phenotypic expression of these genes in clinical settings is yet to be observed. 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-based dressings. Screening of 859 clinical isolates confirmed 31 harbored at least 1 silver resistance gene. Despite the presence of these genes, MIC testing revealed most of the bacteria displayed little or no increase in resistance to ionic silver (200 to 300 ?M Ag(+)). However, 2 isolates (Klebsiella pneumonia and Enterobacter cloacae) were capable of robust growth at exceedingly high silver concentrations, with MIC values reaching 5,500 ?M Ag(+). DNA sequencing of these two strains revealed the presence of genes homologous to known genetic determinants of heavy metal resistance. Darkening of the bacteria's pigment was observed after exposure to high silver concentrations. Scanning electron microscopy images showed the presence of silver nanoparticles embedded in the extracellular polymeric substance of both isolates. This finding suggested that the isolates may neutralize ionic silver via reduction to elemental silver. Antimicrobial testing revealed both organisms to be completely resistant to many commercially available silver-impregnated burn and wound dressings. Taken together, these findings provide the first evidence of clinical bacteria capable of expressing silver resistance at levels that could significantly impact wound management.

SUBMITTER: Finley PJ

PROVIDER: S-EPMC4505248 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Unprecedented Silver Resistance in Clinically Isolated Enterobacteriaceae: Major Implications for Burn and Wound Management.

Finley Phillip J PJ Norton Rhy R Austin Cindy C Mitchell Amber A Zank Sara S Durham Paul P

Antimicrobial agents and chemotherapy 20150526 8

Increased utilization of inorganic silver as an adjunctive to many medical devices has raised concerns of emergent silver resistance in clinical bacteria. Although the molecular basis for silver resistance has been previously characterized, to date, significant phenotypic expression of these genes in clinical settings is yet to be observed. 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 ...[more]

PMID: 26014954

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Project description:Wound infections constitute an increasing clinical problem worldwide. To reverse this trend, several wound dressings with antimicrobial properties have been developed. Considering the increasing presence of antibiotic-resistant microorganisms, product developers have been focusing their efforts in introducing antibiotic-free antibacterial wound dressings to the market, with silver being the most commonly incorporated antimicrobial agent. In this scenario, gaining information about the microbial and eukaryotic cells' response to these dressings is needed for a proper selection of antimicrobial dressings for the different cases of infected wounds. In particular, one insufficiently explored parameter is the effect of the dressings on the immunomodulation of macrophages, the main immune cell population participating in the repair process, because of their pivotal role in the transition of the inflammation to the proliferation phase of wound healing. In this work, three different clinically applied antimicrobial, silver impregnated wound dressings were selected: Atrauman® Ag, Biatain® Alginate Ag and PolyMem WIC Silver® Non-adhesive. Antimicrobial susceptibility tests (disk diffusion and broth dilution), cell viability evaluation (CellTiter-Blue®) and experiments to determine macrophage polarization (e.g., flow cytometry, ELISA and glucose uptake) were performed after 24 h of incubation. Among all products tested, Biatain® Alginate Ag induced the most evident bactericidal effect on Gram-positive and Gram-negative bacteria, followed by PolyMem WIC Silver® Non-adhesive, but did not show good cytocompatibility in vitro. On the other hand, Atrauman® Ag showed excellent cytocompatibility on L929 fibroblasts, HaCaT keratinocytes and THP-1 derived macrophages, but no significant antimicrobial activity was observed. Overall, it was confirmed that macrophages initiate, in fact, an alteration of their metabolism and phenotype in response to wound dressings of different composition in a short period of contact (24 h). M0 resting state macrophages common response to all silver-containing dressings used in this study was to increase the production of the anti-inflammatory cytokine TGF-?, which indicates an acquisition of M2-like macrophages characteristics.

Dataset Information

Unprecedented Silver Resistance in Clinically Isolated Enterobacteriaceae: Major Implications for Burn and Wound Management.

Publications

Unprecedented Silver Resistance in Clinically Isolated Enterobacteriaceae: Major Implications for Burn and Wound Management.

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