In vitro efficacy of copper and silver ions in eradicating Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Acinetobacter baumannii: Implications for on-site disinfection for hospital infection control

Huang, Hsin-I; Shih, H. Y.; Lee, Chien-Ming; Yang, Thomas C.; Lay, Jiunn‐Jyi; Yuan, Lin

doi:10.1016/j.watres.2007.07.003

Cited by 71 publications

(44 citation statements)

References 13 publications

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“…Different works have reported conditions where both synergistic and antagonist effects have been observed between Ag-Cu, the interaction depends on the bacterial species treated 59 . In this work, it can be observed that for the case of Gram-negative E. coli , most of the STMCs showed strong synergistic effects.…”

Section: Resultsmentioning

confidence: 97%

Synergistic Antimicrobial Effects of Silver/Transition-metal Combinatorial Treatments

Garza-Cervantes

Chávez‐Reyes²,

Castillo

et al. 2017

Sci Rep

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Due to the emergence of multi-drug resistant strains, development of novel antibiotics has become a critical issue. One promising approach is the use of transition metals, since they exhibit rapid and significant toxicity, at low concentrations, in prokaryotic cells. Nevertheless, one main drawback of transition metals is their toxicity in eukaryotic cells. Here, we show that the barriers to use them as therapeutic agents could be mitigated by combining them with silver. We demonstrate that synergism of combinatorial treatments (Silver/transition metals, including Zn, Co, Cd, Ni, and Cu) increases up to 8-fold their antimicrobial effect, when compared to their individual effects, against E. coli and B. subtilis. We find that most combinatorial treatments exhibit synergistic antimicrobial effects at low/ non-toxic concentrations to human keratinocyte cells, blast and melanoma rat cell lines. Moreover, we show that silver/(Cu, Ni, and Zn) increase prokaryotic cell permeability at sub-inhibitory concentrations, demonstrating this to be a possible mechanism of the synergistic behavior. Together, these results suggest that these combinatorial treatments will play an important role in the future development of antimicrobial agents and treatments against infections. In specific, the cytotoxicity experiments show that the combinations have great potential in the treatment of topical infections.

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Section: Resultsmentioning

confidence: 97%

Synergistic Antimicrobial Effects of Silver/Transition-metal Combinatorial Treatments

Garza-Cervantes

Chávez‐Reyes²,

Castillo

et al. 2017

Sci Rep

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“…Few published studies have investigated copper resistance levels in A. baumannii, and most prior studies examined environmental isolates of Acinetobacter spp. (29)(30)(31)(32)(33). A single study examined clinical isolates of A. baumannii, and it found that MICs for copper in rich medium were in the millimolar range (16).…”

Section: Resultsmentioning

confidence: 99%

Copper Resistance of the Emerging Pathogen Acinetobacter baumannii

Williams

Neu

Gilbreath

et al. 2016

Appl Environ Microbiol

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Acinetobacter baumannii is an important emerging pathogen that is capable of causing many types of severe infection, especially in immunocompromised hosts. Since A. baumannii can rapidly acquire antibiotic resistance genes, many infections are on the verge of being untreatable, and novel therapies are desperately needed. To investigate the potential utility of copper-based antibacterial strategies against Acinetobacter infections, we characterized copper resistance in a panel of recent clinical A. baumannii isolates. Exposure to increasing concentrations of copper in liquid culture and on solid surfaces resulted in dose-dependent and strain-dependent effects; levels of copper resistance varied broadly across isolates, possibly resulting from identified genotypic variation among strains. Examination of the growth-phase-dependent effect of copper on A. baumannii revealed that resistance to copper increased dramatically in stationary phase. Moreover, A. baumannii biofilms were more resistant to copper than planktonic cells but were still susceptible to copper toxicity. Exposure of bacteria to subinhibitory concentrations of copper allowed them to better adapt to and grow in high concentrations of copper; this copper tolerance response is likely achieved via increased expression of copper resistance mechanisms. Indeed, genomic analysis revealed numerous putative copper resistance proteins that share amino acid homology to known proteins in Escherichia coli and Pseudomonas aeruginosa. Transcriptional analysis revealed significant upregulation of these putative copper resistance genes following brief copper exposure. Future characterization of copper resistance mechanisms may aid in the search for novel antibiotics against Acinetobacter and other highly antibiotic-resistant pathogens. IMPORTANCEAcinetobacter baumannii causes many types of severe nosocomial infections; unfortunately, some isolates have acquired resistance to almost every available antibiotic, and treatment options are incredibly limited. Copper is an essential nutrient but becomes toxic at high concentrations. The inherent antimicrobial properties of copper give it potential for use in novel therapeutics against drug-resistant pathogens. We show that A. baumannii clinical isolates are sensitive to copper in vitro, both in liquid and on solid metal surfaces. Since bacterial resistance to copper is mediated though mechanisms of efflux and detoxification, we identified genes encoding putative copper-related proteins in A. baumannii and showed that expression of some of these genes is regulated by the copper concentration. We propose that the antimicrobial effects of copper may be beneficial in the development of future therapeutics that target multidrug-resistant bacteria.

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“…Metal compounds and complexes of palladium, platinum, copper, gold and silver have been shown to demonstrate effective antimicrobial efficacies against a broad range of AMR pathogens 5, 6, 10, 19 . Metals such as silver in wound dressings, copper on touch surfaces of patient equipment and gold and palladium coatings on catheters are considered to possess potential antimicrobial properties to reduce bacterial infection and transmission risks 24–26 . However, few studies have demonstrated the antimicrobial efficacy of platinum, gold and palladium in their ionic forms or in combination, although their complexes (tetradentate macrocyclic, cisplatin, etc.)…”

Section: Discussionmentioning

confidence: 99%

Antimicrobial Efficacy and Synergy of Metal Ions against Enterococcus faecium, Klebsiella pneumoniae and Acinetobacter baumannii in Planktonic and Biofilm Phenotypes

Vaidya

McBain

Butler

et al. 2017

Sci Rep

132

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The effects of metal ion solutions (silver, copper, platinum, gold and palladium) were determined individually and in combination against Enterococcus faecium, Acinetobacter baumannii and Klebsiella pneumoniae. Platinum, gold and palladium showed the greatest antimicrobial efficacy in zone of inhibition (ZoI) assays. When tested in combinations using ZoI assays, gold/platinum, gold/palladium and platinum/palladium were indicative of synergy. Microbial inhibitory concentration demonstrated platinum and gold against Enterococcus faecium, platinum against Klebsiella pneumoniae and platinum and silver against Acinetobacter baumannii were optimal. Minimal bactericidal concentrations determined the greatest bactericidal activity was again platinum gold and palladium against all three bacteria. Fractional Inhibitory Concentration (FIC) studies demonstrated that the silver/platinum combination against Enterococcus faecium, and silver/copper combination against Acinetobacter baumannii demonstrated antimicrobial synergy. Following crystal violet biofilm assays for single metal ion solutions, antimicrobial efficacies were demonstrated for all the metals against all the bacteria Synergistic assays against biofilms demonstrated gold/palladium, gold/platinumand platinum/palladium resulted in the greatest antimicrobial efficacy. Overall, platinum, palladium and gold metal ion solutions in individual use or combination demonstrated the greatest antimicrobial efficacies against planktonic or biofilm bacteria. This work demonstrates the potential for using a range of metal ions, as biocidal formulations against both planktonic or biofilm bacteria.

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In vitro efficacy of copper and silver ions in eradicating Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Acinetobacter baumannii: Implications for on-site disinfection for hospital infection control

Cited by 71 publications

References 13 publications

Synergistic Antimicrobial Effects of Silver/Transition-metal Combinatorial Treatments

Synergistic Antimicrobial Effects of Silver/Transition-metal Combinatorial Treatments

Copper Resistance of the Emerging Pathogen Acinetobacter baumannii

Antimicrobial Efficacy and Synergy of Metal Ions against Enterococcus faecium, Klebsiella pneumoniae and Acinetobacter baumannii in Planktonic and Biofilm Phenotypes

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