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Physicochemical properties of copper important for its antibacterial activity

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DOI: 10.1116/1.4935853

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Physicochemical properties of copper important for its antibacterial activity and
development of a unified model
Michael Hans, Salima Mathews, Frank Mücklich, and Marc Solioz

Citation: Biointerphases 11, 018902 (2016); doi: 10.1116/1.4935853

View online: http://dx.doi.org/10.1116/1.4935853
View Table of Contents: http://scitation.aip.org/content/avs/journal/bip/11/1?ver=pdfcov
Published by the AVS: Science & Technology of Materials, Interfaces, and Processing

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Physicochemical properties of copper important for its antibacterial activity
and development of a unified model
Michael Hans
Functional Materials, Saarland University, Saarbr€
ucken 66123, Germany
Salima Mathews
Department of Clinical Research, University of Bern, Bern 3008, Switzerland
€cklich
Frank Mu
Functional Materials, Saarland University, Saarbr€
ucken 66123, Germany
Marc Solioza)
Laboratory of Biochemistry and Molecular Biology, Tomsk State University, Tomsk 634050,
Russian Federation
(Received 1 October 2015; accepted 4 November 2015; published 16 November 2015)
Contact killing is a novel term describing the killing of bacteria when they come in contact with
metallic copper or copper-containing alloys. In recent years, the mechanism of contact killing has
received much attention and many mechanistic details are available. The authors here review some
of these mechanistic aspects with a focus on the critical physicochemical properties of copper
which make it antibacterial. Known mechanisms of contact killing are set in context to ionic, corro-
sive, and physical properties of copper. The analysis reveals that the oxidation behavior of copper,
paired with the solubility properties of copper oxides, are the key factors which make metallic cop-
per antibacterial. The concept advanced here explains the unique position of copper as an antibacte-
rial metal. Based on our model, novel design criteria for metallic antibacterial materials may be
C 2015 American Vacuum Society. [http://dx.doi.org/10.1116/1.4935853]
derived. V

I. INTRODUCTION Classical copper-containing alloys are brass and bronze and

According to the latest Surveillance Report of the have been used for centuries. Metallic silver surfaces exhibit
European Centre for Disease Prevention and Control and the only very poor antibacterial activity,7 but silver or silver ox-
WHO report on Patient Safety, on any given day, 80 000 ide in the form of nanoparticles efficiently kills bacteria,
patients in European hospitals have a hospital acquired which is also true for copper or copper oxide nanoparticles.
infection and an estimated 100 deaths per day result from Here, nanoparticles will not be discussed in depth. The large
these infections.1,2 In healthcare facilities, infectious bacteria surface to volume ratio of nanoparticles invokes very differ-
can be transmitted via contact surfaces such as door handles, ent physicochemical properties and near-surface phenomena.
bed rails, armrests of chairs, bathroom fixtures, etc. It has Additionally, nanoparticle–bacterial interactions may play
been shown that many bacteria, including the dangerous an important role in the killing mechanism, which may thus
methicillin resistant Staphylococcus aureus, can survive for not be comparable to that of solid, metallic surfaces (see
months on plastic, stainless steel, and similar surfaces and Franci et al. for a recent review on nanoparticles8).
constitute a source of infection.3,4 Obviously, extensive
cleaning and disinfection protocols are in place in all modern II. BRIEF HISTORY OF ANTIBACTERIAL COPPER
health care facilities. However, this does not provide full The use of copper as an antibacterial material can be
protection. Recontamination will occur between cleaning dated back several millennia. Around 2400 BC, copper pow-
cycles, and disinfection can be flawed by human error or der was used for wound disinfection in ancient Egypt.9
negligence. In addition, many common items like keyboards, Copper preparations continued to be used throughout the
computer mice, cell phones, and pens, are often not disin- millennia until penicillin became widely available to the
fected or not on a regular basis and can therefore be a signifi- public in 1945. Anew interest in copper as an antibacterial
cant source of bacterial contamination.5 This calls for agent was sparked by a 1983 study in a hospital, showing
complementary strategies. that viable Escherichia coli were present on stainless steel
One such strategy is the use of materials which possess an door knobs, while they were absent on brass door knobs.10
intrinsic antibacterial activity. In this context, copper and Many studies on the antibacterial properties of copper have
copper alloys, due to their excellent, intrinsic antibacterial since been conducted, culminating in the registration of cop-
properties, have emerged as a bona fide solution to the prob- per and copper alloys as antibacterial agents (“pesticides”)
lem. The antibacterial activity of copper is maintained in with the U.S. Environmental Protection Agency in 2008.6
alloys as long as they contain 60% or more copper.6 In the light of increasing hospital-acquired infections, this
led to a number of studies employing copper for tables,
a)
Electronic mail: [email protected] armrests, IV poles, etc., in hospital wards in different

018902-1 Biointerphases 11(1), March 2016 1934-8630/2016/11(1)/018902/8/$30.00 C 2015 American Vacuum Society
V 018902-1
018902-2 Hans et al.: Physicochemical properties of copper important for its antibacterial activity 018902-2

countries and which show very promising results.11–16 Such bacterial membrane as a key event in contact killing. Damage
approaches are not only of interest in healthcare settings, but of the cell envelope has been documented for several organ-
also in food-processing facilities.17,18 Finally, copper finds isms and by different techniques such as direct microscopic
increasing use in the design of antibacterial textiles.19 While examination of cells, staining of cells with redox dyes, stain-
these efforts continue, new copper alloys have appeared on ing of respiring cells, or by showing membrane depolariza-
the market to meet modern design criteria in terms of color tion.24–29 Figure 2 shows extensive structural damage inflicted
and material properties. Today, many fittings and objects on Enterococcus hirae after prolonged exposure to a copper
made of copper or copper alloys are on the market, including surface in experiments conducted in our laboratories. A tech-
door knobs, push plates, bathroom fixtures, toilet seats, cop- nique called “Live/Dead” staining has also been frequently
per pens, light switches, keyboards, etc. (Fig. 1). Also, anti- used. It combines the green fluorescent SYTO9 DNA dye,
microbially functionalized materials have emerged, such as which is membrane permeable and stains all cells, with red
plastics doped with copper or silver, or fabrics impregnated fluorescent propidium iodide, entering only damaged cells and
with copper oxide. This has extended the scientific view staining cellular DNA with higher affinity than SYTO9. This
from a purely microbiological approach to an interdiscipli- changes the fluorescence of dying and dead cells from green
nary task, including materials science aspects. to red.28,30 Damage of the cell envelope of E. coli by metallic
copper is also supported by proteomic profiling: proteins
III. HOW BACTERIA ARE KILLED ON COPPER involved in cell envelope synthesis and capsule polysaccha-
SURFACES ride biogenesis are upregulated upon contact with copper.31
Following membrane damage, there is massive influx of
Contact killing by copper has been shown for at least 90 copper ions into the bacterial cytoplasm.25,29 Using a cyto-
bacterial species, 30 types of fungi, and 20 different viruses, plasmic copper sensor, Espırito Santo et al. measured the
and it can safely be assumed that all bacteria and viruses are cellular copper content in Staphylococcus to be 2.6  1010
sensitive to contact killing.6,20 Various possible mechanisms copper ions per cell 5 min after contact with a dry copper
for contact killing by copper have been published.6,21 Four surface.32 In line with this, it has been observed that copper
toxicity mechanisms which participate in contact killing have chelators such as bicinchoninic acid, bathocuproine disulfo-
been identified: (1) damage of the outer and/or inner bacterial nate, or ethylenediamine tetra acetic acid significantly inhibit
membrane, (2) oxidative damage by reactive oxygen species or even prevent contact killing.28,33 Also, E. coli cells unable
(ROS), (3) inhibition of essential enzymes, and (4) degrada- to synthesize glutathione, which constitutes a major defense
tion of deoxyribo nucleic acid (DNA). It appears that there is against toxic heavy metal ions, were more sensitive to con-
variation as to the key toxic principle, depending on the exper- tact killing than wild-type cells.34 Of special interest is the
imental system and the organism under investigation. recent observation that Cuþ is considerably more toxic to
Release of ionic copper from the surface is clearly a key bacteria than Cu2þ, an aspect that directly bears on copper’s
event in contact killing.22 The second mechanistically impor- antibacterial activity (see below).35
tant aspect is bacteria–metal contact.23 These events are Clearly, the main toxicity mechanisms of copper and cop-
believed to induce severe damage of the outer and/or inner per alloys is the release of copper ions into the aqueous

FIG. 1. Copper items available on the market. For a listing of suppliers, see http://www.antimicrobialcopper.com/uk/find-products-and-services/find-antimicro-
bial-copper-products.aspx.

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018902-3 Hans et al.: Physicochemical properties of copper important for its antibacterial activity 018902-3

FIG. 2. Structural damage inflicted on E. hirae on a copper surface. (a) E. hirae immediately after contact with a metallic copper surface. Note how the cells
tend to snug into groves on the copper surface. (b) Structural damage to E. hirae by the copper surface after 1 h of exposure. The pictures show scanning elec-
tron micrographs of unstained, air-dried cells.

phase; even in so-called “dry” applications of bacteria to On one hand, ROS quenchers were found to inhibit contact
copper surfaces, there will be an aqueous phase surrounding killing to some extent, on the other hand, killing is appa-
the bacteria. In line with this, surface roughness also influen- rently not impaired by anaerobic conditions which disfavor
ces contact killing: rough surfaces release more copper ions ROS production.33,42
per time and are more antibacterial than polished surfaces.36 With regard to copper toxicity mechanisms in bacteria, a
But bacteria–metal contact also appears to play a role in con- distinction has to be made between cells in culture and cells
tact killing. It was found that the killing of E. hirae on cop- exposed to metallic copper. In culture, cells are in a growing
per surfaces was drastically reduced when bacteria–metal state while during exposure to copper surfaces, they are in a
contact was prevented by an inert grid, even though copper non-growing state. When studying copper toxicity in culture,
ion release remained unchanged.23 This shows that contact only relatively low amounts of copper enter the cell. Under
killing by copper surfaces is not a simple phenomenon of these conditions, the toxic effect in E. coli was shown to be
copper ion toxicity to bacteria, but is influenced by bacter- the displacement of iron from [4Fe-4S] clusters of essential
ia–metal contact, corrosion phenomena, surface structure, enzymes, rather than ROS production and oxidative dam-
nobility of alloying metals, and last, but not least, the bacte- age.43–46 Attack of [4Fe-4S] clusters was also demonstrated
rial species under investigation. for Ag(I), Hg(II), Cd(II), and Zn(II) at concentrations which
In the presence of oxygen, copper ions can cycle between only minimally inhibited cell growth.47 In line with this tox-
the Cuþ and Cu2þ oxidation state (1) icity mechanism, the toxicity of metal ions was directly
related to their thiophilicity (see below). Different principles
Cuþ ! Cu2þ þ e ðE ¼ 0:16 VÞ: (1) obviously underlie the inactivation of viruses, where capsid
and nucleic acid damage by copper have been demon-
This reactivity can lead to the generation of ROS by a strated.48–50 This will not be further considered here.
Fenton-type reaction (2)37 Bacteria which come into contact with a copper surface
under contact killing conditions are starved for nutrients and
Cuþ þ H2 O2 ! Cu2þ þ OH þ OH• : (2)
are killed in the absence of growth. The most likely scenario
Combined with the Haber–Weiss cycle [(3) and (4)], this can of contact killing is thus the following: as a primary event,
provide a rich source of ROS, particularly in lactic acid bac- there is severe damage to the cell envelope and the cytoplas-
teria, which can produce large amounts of hydrogen mic membrane; this is followed by massive influx of copper
peroxide38,39 ions into the cell and damage of intracellular components,
including DNA, by multiple mechanisms. The importance of
H2 O2 þ OH• ! H2 O þ O2  þ Hþ ; (3) each toxicity mechanism and the sequence of events seems to
  • vary between species and between eukaryotes, prokaryotes,
H2 O2 þ O2 ! O2 þ OH þ OH : (4)
and viruses. For cells, it emerges that copper toxicity in con-
Reaction (4) by itself has a negligible rate constant, but is tact killing is mechanistically different from the toxicity in
catalyzed by Cu(II) or Fe(III) complexes. ROS are well growing cultures. The situation is also distinct from biofilms,
known to cause irreversible cell damage by a variety of which form on surfaces over extended periods of time and
mechanisms, such as by inhibition of respiration, lipid per- require growth and attachment of the cells to the substrate.
oxidation, and oxidative damage of proteins.31 ROS produc-
tion was demonstrated for E. coli and Salmonella exposed to IV. THIOPHILICITY AND TOXICITY
solid copper.40,41 However, to what extent ROS production In the “hard and soft acid and base” (HSAB) concept of
is important for contact killing remains an issue of debate. Pearson, ions are classified as “hard” if they have a high

Biointerphases, Vol. 11, No. 1, March 2016

018902-4 Hans et al.: Physicochemical properties of copper important for its antibacterial activity 018902-4

TABLE I. Selected properties of metals ordered by oxide solubility. contact killing. But other parameters like solubility, uptake
by bacteria, and cellular defense mechanisms can play an
Ionic properties Corrosion behavior
overriding role, depending on the experimental conditions.
Element/ion HSABa pKS(MeS)b E0 (V)c pKS[MeO/Me(OH)]d
V. CRITICAL PHYSICOCHEMICAL PARAMETERS
Ag(I) S 50.2 0.79 7.7
IN CONTACT KILLING
Cu(I) S 47.6 0.52 9.0
Cd(II) S 26.1 0.40 13.6 A major issue to consider is the effect of copper surface
Co(II) I 20.4 0.28 14.2 oxidation. Under atmospheric conditions, copper oxidation
Ni(II) I 18.5 0.26 14.7 takes place in several steps. The Pourbaix-diagram [Fig.
Fe(II) I 18.2 0.41 15.1 3(a)] describes the electrochemical corrosion behavior of
Pb(II) I 27.5 0.13 15.2 copper in water from a thermodynamic point of view.56 It
Zn(II) I 25.7 0.76 16.4
shows how the speciation of copper depends on the reduc-
Cu(II) I 36.2 0.34 23.5
tion potential Eh (positive for oxidizing conditions, nega-
Hg(II) S 52.7 0.80 25.4
Sn(II) H 26.0 0.14 26.2
tive for reducing conditions) and the pH. Under conditions
Al(III) H Unstable 1.66 32.9 encountered in the biosphere [hatched areas in Fig. 3(a)],
Fe(III) H Unstable 0.02 37.4 both, Cu2O and CuO, can form. Oxidizing conditions (clean
Au(III) S nae 1.49 na water in air, upper hatched area) favor formation of CuO,
Pt(II) S 26.1 1.18 99.8f while reducing conditions (presence of organic matter, bac-
Pd(II) S 21.2 0.95 120.3f teria) favor Cu2O formation. On the other hand, pH values
below six and oxidizing conditions favor dissolution of
Note: na, Value not available.
a
Hardsoft character according to Pearson (Ref. 51): h, hard; i, intermedi- copper oxides to aqueous Cu2þ. Thus, copper oxide forma-
ate, s, soft. tion and stability under real-life conditions can change
b
pKS-values for the solubility product KS of the respective metal sulphide markedly.
[pKS(MeS)]. On a dry copper surface in ambient air and humidity, a
c
Standard electrochemical potential.
d layer of cuprous oxide (Cu2O) is initially formed. This is fol-
pKS-values of the metal oxide or metal hydroxide equilibria {pKS[MeO/Me(OH)]}
(Ref. 52). lowed by a second layer of cupric oxide (CuO).57–60 The for-
e
The thiophilicity of gold appears to be high (Ref. 53). mation of the second CuO layer seems to be favored in a
f
Values from Ref. 54. humid atmosphere and during long aging periods. Thus,
atmospheric copper oxide layers consist of either Cu2O or a
Cu2O/CuO double layer, depending on the oxidation time
charge density (high ratio of charge to radius) and are not and the conditions. In the presence of chloride ions, for
easily polarized, and as “soft” if they have a low charge den- example, the formation of Cuþ, which is more toxic to bacte-
sity (low ratio of charge to radius) and are therefore easily ria than Cu2þ, is favored, and the formation of Cu2O is
polarized.51 Soft ionic species readily form compounds with shifted to more alkaline pH [Fig. 3(b)].61 So, chloride ions
sulphur, a property also termed “thiophilicity.” An attempt from sweat could actually enhance the antibacterial activity
was made here to correlate available formation constants for of copper, but this remains to be demonstrated. Copper com-
metal sulfides, pKS(MeS), with thiophilicity based on the plexing agents such as ammonium, cyanide, or sulfur will al-
HSAB concept (Table I). The correlation between hard/soft ter reaction kinetics even more dramatically, making any
assignments and pKS(MeS) values does not hold up in all prediction very difficult.
cases. Sn, for example, is classified as hard, but exhibits a Various studies, most of them focusing on nanoparticles
relatively high pKS(MeS) of 26. However, it should be noted or coated textile fibers, demonstrate antibacterial activity for
that widely differing values of pKS(MeS) can be found in the both types of copper oxides.62–65 For metallic surfaces, the
literature and the most recent available values were listed in antibacterial activity of Cu2O versus CuO was recently
Table I, assuming that they are the most accurate. investigated.66 It was found that Cu2O exhibited strong anti-
Agþ, Cuþ, Cd2þ, and Hg2þ, which are all very toxic to bacterial properties, whereas CuO showed much slower bac-
growing bacteria, are assigned a soft character and exhibit terial killing. Copper ion release from these surfaces
the expected low pKS(MeS) values. Similarly, Cu2þ, which is correlated with the antibacterial potency. This suggests that
classified as “intermediate” on the HSAB scale, has a the release of copper ions from copper oxides is a key pa-
pKS(MeS) of 36.2, and is less toxic to bacteria than Cuþ rameter in contact killing.
with a pKS(MeS) of 47.6. Au, Pd, and Pt are classified as The solvation of metal oxides is expressed by pKS[MeO/
soft, but these metals are “noble” and do not form solute Me(OH)] in Table I, and the metals are ordered by decreasing
ions under ambient aqueous conditions, which is reflected by values. Among the metal oxides for which solubility con-
low solubility constants and high electrochemical standard stants could be found in the literature, AgO and Cu2O are
potentials, E0, of þ0.95 to þ1.49 V. the most soluble oxides, with pKS values of 7.7 and 9,
Overall, the combined consideration of all these parame- respectively. The solubility of CuO, on the other hand, is
ters may allow some predictions of toxicity in culture or in much lower and in the range of that of other metal oxides.

Biointerphases, Vol. 11, No. 1, March 2016

018902-5 Hans et al.: Physicochemical properties of copper important for its antibacterial activity 018902-5

FIG. 4. Pourbaix diagram for silver. The graph shows the speciation of silver
as a function of reduction potential Eh and pH. The upper and lower dashed
lines indicate the reduction potential of water saturated with oxygen or
hydrogen, respectively, at 1 atm, and the hatched area delineates conditions
encountered in the biosphere.

The higher solubility of Cu2O compared to CuO correlates

with its higher antibacterial activity. By this approach, Cd is
predicted to be a metal with good antibacterial activity: it is
soft, does not have a noble character, has a high thiophilicity,
is toxic to bacteria, and its oxide has a relatively high solu-
bility, based on the pKS[MeO/Me(OH)] value of 13.6. To our
knowledge, contact killing by cadmium has never been
tested. Of course its toxicity precludes any practical applica-
tions, but it would be interesting from an academic point of
view to know its contact killing activity.
In comparison to copper, metallic silver surfaces are dra-
matically less effective in contact killing, and to call them
“antibacterial” is not really justified. To observe efficient
contact killing by metallic silver, long exposure times at
elevated temperature in aqueous environments have to be
used, e.g., 24 h at 37  C, as specified by the Japanese test
procedure JIS Z 2801:2000. This procedure was used by
Kawakami et al.67 and lead to the misleading conclusion
that silver is essentially as active in contact killing as cop-
per. But if short exposures (e.g., 1–2 h) at room temperature
are used, silver is essentially ineffective in killing bacteria
or viruses.68–70 Silver is more noble than copper and does
not readily oxidize under ambient conditions, as can be
seen from its Pourbaix diagram (Fig. 4). Only under condi-
tions which promote the formation of silver oxides (e.g.,
FIG. 3. Pourbaix diagrams for copper. The graphs show the speciation of high pH and oxidizing conditions), the antibacterial activity
copper as a function of reduction potential Eh and pH. (a) Copper in of silver surfaces is induced, presumably because the ensu-
water without chloride and carbonate at 25  C. The hatched area delin-
eates conditions encountered in the biosphere (upper part: clean water in
ing AgO has a high solubility, even greater than that of
air, lower part: water with organic matter). (b) Copper in the presence of Cu2O (cf. Table I), and gives off toxic Agþ ions.68 This
0.3 M Cl and carbonate in equilibrium with air. The hatched area delin- also explains the excellent antibacterial activity of silver
eates conditions encountered in the biosphere and the upper and lower oxide nanoparticles. Taken together, for a solid metal sur-
diagonal lines indicates the reduction potential of water saturated with
oxygen or hydrogen, respectively, at 1 atm [Reproduced with permission
face to be antibacterial, it must (1) readily oxidize under
from M. B. McNeil and B. J. Little, J. Am. Inst. Conserv. 31, 355 ambient conditions, and (2) the oxide must be relatively
(1992)] (Ref. 55). soluble to release toxic metal ions.

Biointerphases, Vol. 11, No. 1, March 2016

018902-6 Hans et al.: Physicochemical properties of copper important for its antibacterial activity 018902-6

FIG. 6. Killing of bacteria on iron in the presence of copper. Cells (1–3 

107) of E. hirae wild-type or a DcopAB mutant deficient in copper export
were spread on iron coupons in the absence or presence of 4 mM CuSO4 and
survival was determined at different times. Shown are survival for E. hirae
wild-type without Cu (䊊), E. hirae wild-type plus 4 mM Cu (䊉), a DcopAB
mutant without copper (D), and a DcopAB mutant with 4 mM Cu (䉱).

copper coated with a thin silver layer.72 These studies were

conducted in humid environments, where corrosion can take
place. This suggests that electrochemically driven mecha-
nisms can also enhance the release of copper and/or silver
ions, a strategy that could be further exploited to design
more effective antibacterial materials.
Another electrochemically driven phenomenon in contact
killing was demonstrated in a study by Mathews et al.42
Metallic iron surfaces are not antibacterial, which is again
apparent from the Pourbaix diagram: under ambient condi-
FIG. 5. Pourbaix diagram for iron. The graphs shows the speciation of iron
as a function of reduction potential Eh and pH. The hatched areas delineate tions, iron does not form any oxides which are soluble
conditions encountered in the biosphere [upper part: clean water in air, (Fig. 5). However, if a subtoxic concentration of CuSO4 is
lower part: water with organic matter; reproduced with permission from added to the system, rapid killing of bacteria occurs (Fig. 6).
M. B. McNeil and B. J. Little, J. Am. Inst. Conserv. 31, 355 (1992)] (Ref. 55). The effect was shown to be due to the reduction of Cu2þ to
the more toxic Cuþ by the iron surface.42 A mutant deficient
VI. ELECTROCHEMICAL PHENOMENA in Cuþ export was considerably more sensitive to killing than
IN CONTACT KILLING wild-type cells, underlining the importance of copper ions in
It was shown that a copper alloy containing 10% silver the killing process. Cuþ ions could also play a key role in
exhibited enhanced contact killing compared to pure cop- “normal” contact killing by copper, where the dissolution of
per.71 This correlated with increased copper ion release. Jing copper oxides could lead to the generation of Cuþ. This
et al. also demonstrated increased bactericidal activity of would be an interesting aspect to address experimentally.

FIG. 7. Schematic of the key factors required for the antibacterial activity of a metal.

Biointerphases, Vol. 11, No. 1, March 2016

018902-7 Hans et al.: Physicochemical properties of copper important for its antibacterial activity 018902-7

20
VII. SUMMARY AND CONCLUSION G. Borkow, Curr. Chem. Biol. 6, 93 (2012).
21
G. Borkow and J. Gabbay, Curr. Med. Chem. 12, 2163 (2005).
Copper is the only element for which rapid contact killing 22
C. Molteni, H. K. Abicht, and M. Solioz, Appl. Environ. Microbiol. 76,
of bacteria by a solid metallic surface has been demon- 23
4099 (2010).
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Microbiol. 79, 2605 (2013).
three key properties of copper: (1) copper oxidizes under 24
C. Espirito Santo, E. W. Lam, C. G. Elowsky, D. Quaranta, D. W.
ambient conditions, e.g., in air of moderate humidity, (2) the Domaille, C. J. Chang, and G. Grass, Appl. Environ. Microbiol. 77, 794
copper oxides thus formed are soluble in the aqueous phase, 25
(2011).
and (3) the copper ions released by the oxides are toxic to W. X. Tian, S. Yu, M. Ibrahim, A. W. Almonaofy, L. He, Q. Hui, Z. Bo,
B. Li, and G. L. Xie, J. Microbiol. 50, 586 (2012).
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J. O. Noyce, H. Michels, and C. W. Keevil, J. Hosp. Infect. 63, 289
ity. Surface contact or proximity may play an additional role (2006).
27
(Fig. 7). Even in so-called dry exposure of bacteria to cop- S. L. Warnes, S. M. Green, H. T. Michels, and C. W. Keevil, Appl.
per, there will be an aqueous phase surrounding the bacteria, Environ. Microbiol. 76, 5390 (2010).
28
S. L. Warnes and C. W. Keevil, Appl. Environ. Microbiol. 77, 6049
allowing the above processes to take place. Taking these (2011).
concepts into consideration, it should be possible to develop 29
D. Quaranta, T. Krans, C. Espirito Santo, C. G. Elowsky, D. W. Domaille,
alloys in which additional electrochemical effects lead to 30
C. J. Chang, and G. Grass, Appl. Environ. Microbiol. 77, 416 (2011).
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Microbiol. 109, 2200 (2010).
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R. Nandakumar, C. Espirito Santo, N. Madayiputhiya, and G. Grass,
play good contact killing and should be tested for proof-of- Biometals 24, 429 (2011).
32
principle. C. Espırito Santo, D. Quaranta, and G. Grass, MicrobiologyOpen 1, 46
(2012).
33
C. Espirito Santo, N. Taudte, D. H. Nies, and G. Grass, Appl. Environ.
ACKNOWLEDGMENTS Microbiol. 74, 977 (2008).
34
The authors acknowledge supported by a Russian C. Grosse, G. Schleuder, C. Schmole, and D. H. Nies, Appl. Environ.
Microbiol. 80, 7071 (2014).
Federation Government grant to leading scientists (Contract 35
H. K. Abicht, Y. Gonskikh, S. D. Gerber, and M. Solioz, Microbiology
No. 14.Z50.31.0011) and the German Research Foundation 159, 1190 (2013).
36
(Project No. MU959/31). M. Zeiger, M. Solioz, H. Edongue, E. Arzt, and A. S. Schneider,
MicrobiologyOpen 3, 327 (2014).
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