Antimicrobial activity of copper surfaces against carbapenemase-producing contemporary Gram-negative clinical isolates

Souli, María; Galani, Irene; Plachouras, Diamantis; Panagea, Theofano; Armaganidis, Apostolos; Petrikkos, George; Giamarellou, Helen

doi:10.1093/jac/dks473

Cited by 55 publications

(47 citation statements)

References 21 publications

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“…2). A. baumannii clinical isolates have previously been shown to be sensitive to copper-containing metal coupons (50)(51)(52). The data cannot be compared directly due to protocol differences, but similar trends were observed, with full survival on control surfaces, significant reductions on coppercontaining surfaces, and more efficient killing by alloys with a higher copper content.…”

Section: Figmentioning

confidence: 90%

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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Section: Figmentioning

confidence: 90%

Copper Resistance of the Emerging Pathogen Acinetobacter baumannii

Williams

Neu

Gilbreath

et al. 2016

Appl Environ Microbiol

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“…According to our results, 99 % copper exhibited the highest reduction of microorganisms and the significance was particularly apparent at 0, 2, and 4 h time intervals. The bactericidal effect of 99 % copper was shorter than the other studies that have evaluated multidrug-resistant bacteria [2,7,22,23]. Two separate studies, Warnes and Keevil [26] and Santo et al [20], recently published that killing of bacteria on a dry copper surface can be as short as 2-10 min.…”

Section: Discussionmentioning

confidence: 98%

“…In an attempt to mimic in vivo conditions, various laboratory-based studies have used numerous methods to show the efficacy of copper against pathogenic organisms [13,22]. There are mainly two wet and dry inoculation techniques used in studies and it has been shown that temperature, humidity, the copper content of alloys and the dry technique increase the efficacy of copper contact killing [8].…”

Section: Discussionmentioning

confidence: 99%

“…Copper is an essential element at low concentrations as a cofactor for living organisms. The utilization of copper alloys at high concentrations proved to exhibit toxic effects by contact killing most microorganisms [5,18,22]. Copper and many copper alloys have already been registered at the U.S. Environmental Protection Agency (EPA) in 2008 as the first solid antimicrobial material.…”

Section: Introductionmentioning

confidence: 99%

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Antimicrobial Activity of Copper Alloys Against Invasive Multidrug-Resistant Nosocomial Pathogens

2015

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The emergence and spread of antibiotic resistance demanded novel approaches for the prevention of nosocomial infections, and metallic copper surfaces have been suggested as an alternative for the control of multidrug-resistant (MDR) bacteria in surfaces in the hospital environment. This study aimed to evaluate the antimicrobial activity of copper material for invasive MDR nosocomial pathogens isolated over time, in comparison to stainless steel. Clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) (n:4), OXA-23 and OXA-58 positive, MDR Acinetobacter baumannii (n:6) and Pseudomonas aeruginosa (n:4) were evaluated. The antimicrobial activity of coupons containing 99 % copper and a brass alloy containing 63 % copper was assessed against stainless steel. All the materials demonstrated statistically significant differences within each other for the logarithmic reduction of microorganisms. Among the three materials, the highest reduction of microorganisms was seen in 99 % copper and the least in stainless steel. The result was statistically significant especially for 0, 2, and 4 h (P = 0.05). 99 % copper showed a bactericidal effect at less than 1 h for MRSA and at 2 h for P. aeruginosa. 63 % copper showed a bactericidal effect at 24 h for P. aeruginosa strains only. Stainless steel surfaces exhibited a bacteriostatic effect after 6 h for P. aeruginosa strains only. 99 % copper reduced the number of bacteria used significantly, produced a bactericidal effect and was more effective than 63 % copper. The use of metallic copper material could aid in reducing the concentration of bacteria, especially for invasive nosocomial pathogens on hard surfaces in the hospital environment.

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“…Other researchers observed that Cu could displace Fe atoms from dehydratase Fe-S clusters and block branched-chain amino acid synthesis in E. coli 37) . Various scientific studies account for the beneficial use of copper and its alloys, most notably with its multitoxicity, which also renders copper effective against multiresistant germs like the "superbug" MRSA (methicillin resistant Staphylococcus aureus) 38) or carbapenemase-resistant bacteria 39) . On the other hand, we know that a high concentration of Cu can cause upset stomach, nausea and diarrhea and can lead to tissue injury and disease 40) .…”

Section: Discussionmentioning

confidence: 99%

The anti-bacterial activity of titanium-copper sintered alloy against <i>Porphyromonas gingivalis</i> <i>in vitro </i>

Bai

Zhang

Liu

et al. 2016

Dental Materials Journal

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This study investigates the anti-bacterial property of Ti-Cu sintered alloys against Porphyromonas gingivalis. The anti-anaerobic property of Ti-Cu sintered alloys against P. gingivalis was investigated by antibacterial activity test, DNA measurement, DAPI staining and morphology observation. The antibacterial rates of the Ti-5Cu against P. gingivalis after 18 and 24 h incubation were 36.04 and 54.39%, and those of Ti-10Cu were 68.69 and 75.39%, which were lower than their anti-aerobic abilities. The concentration of P. gingivalis DNA gradually decreased with the increasing Cu content, which was nearly 50% after 24 h incubation on Ti-10Cu. SEM results showed that the shape of P. gingivalis changed and the bacteria broke apart with the addition of Cu and the extension of the culture time. Ti-Cu sintered alloys could not only kill anaerobic bacteria but also reduce the activity of the survived bacteria. The anti-anaerobic mechanism was thought to be in associated with the Cu ion released from Ti-Cu alloy.

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Antimicrobial activity of copper surfaces against carbapenemase-producing contemporary Gram-negative clinical isolates

Cited by 55 publications

References 21 publications

Copper Resistance of the Emerging Pathogen Acinetobacter baumannii

Copper Resistance of the Emerging Pathogen Acinetobacter baumannii

Antimicrobial Activity of Copper Alloys Against Invasive Multidrug-Resistant Nosocomial Pathogens

The anti-bacterial activity of titanium-copper sintered alloy against <i>Porphyromonas gingivalis</i> <i>in vitro </i>

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