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The Antimicrobial
Effect of Metal
By Andre Hsiung
Andre Hsiung is the director
of technical services at
Hardy Diagnostics. He is
responsible for the technical
support team and the
quality control laboratory.
Mr. Hsiung earned his
master’s degree in
microbiology while studying
antimicrobial resistance of
Gram-negative bacteria in
Brazil.
Hardy Diagnostics
T
binding to reactive groups,
resulting in their precipitation
and inactivation. For instance,
silver inactivates enzymes by
reacting with the thiol groups
to form silver sulfides. Silver
also reacts with the amino-,
carboxyl-, phosphate-, and
imidazole-groups and
diminishes the activity of key
enzymes that are necessary
for the metabolic activities of
the bacteria.
Although the exact
mechanism of action is still
not known, bacteria are in
general more affected by this
oligodynamic effect than
viruses. This disparity
suggests that, in general, the
mechanisms exerting the most
influence over toxicity are
interfering with metabolism,
since viruses are not
considered to be metabolically
active outside their host range,
this is the reason they are less
affected by the oligodynamic
effect.
Human Applications
he antimicrobial effect
of metals such as
mercury, silver, copper, iron,
lead, zinc, bismuth, gold, and
aluminum, among others has
been demonstrated since the
late 1800s. It is known as the
oligodynamic effect (Greek:
oligos = few, Greek: dynamis
= force). Several metal ions,
especially heavy metals, show
this effect to various degrees.
In general, metal ions
denature enzymes of the
target cell or organism by
As far as human applications
are concerned, the
oligodynamic effect of metals
can be illustrated with a wide
variety of examples:
Developed by Paul Ehrlich in
Germany in 1909, arsenic was used
as an anti-syphilis drug, known as
Salvarsan, until the 1940s.
Arsenic was the first
antimicrobial used against
syphilis.
Despite its toxicity, mercury
is still used today as a
preservative in vaccines.
Brass is an alloy of copper and
zinc. Copper is known for its
antimicrobial properties and can be
useful for infection control.
Thimerasol, a mercury containing
compound is currently used in
many vaccines to prevent
contamination. It is thought by
some to be a contributing factor to
autism in children.
Brass doorknobs disinfect
themselves in about eight
hours, while stainless steel
and aluminum knobs have
limited activity. Therefore,
unvarnished brass doorknobs
tend to be more sanitary than
stainless or aluminum
doorknobs. This effect is
especially important in
hospitals, and recommended
for any other building.
Silver is capable of rendering
stored drinking water potable
for several months. For this
reason, water tanks on ships
and airplanes are often
"silvered." This practice dates
back to the ancient
Phoenicians.
It used to be a common
practice to place a silver
dollar in a milk bottle to help
keep the milk from spoiling.
In 1884, it became a common
practice to administer drops of
aqueous silver nitrate to a
newborn's eyes to prevent the
transmission of Neisseria
gonorrhoeae from infected
mothers to children during
childbirth.
Although silver nitrate was used
successfully to prevent blindness in
newborns for many years,
erythromycin is now used as a
better choice since it is effective
against chlamydia as well as N.
gonorrhoeae.
Silver compounds such as
silver sulfadiazine are used
externally in wound and burn
treatments. Silver
nanoparticles, obtained by
irradiating a silver nitrate
solution with an electron
beam, are effective
bactericides, destroying gramnegative species immune to
conventional antibacterial
agents.
Silver-coated medical
implants and devices have
been shown to be more
resistant to biofilm formation.
Figure 1: An ionic silver coating is
bonded to titanium alloys on
surgical implants in order to
prevent post-operative infections.
Furunculosis, an infection seen
in farmed salmon, has become
increasingly resistant to
medications.
Silver nitrate has been shown
to be effective in inhibiting
the development of the herpes
simplex type 1 virus, though it
is largely ineffective against
type 2. It has also been used
with success against common
skin warts.
Industrial Applications
To take advantage of the
oligodynamic properties,
addition of metals is common
practice in a wide variety of
industries as antimicrobial or
anti-fouling agents. For
instance, land application of
metal containing fertilizers,
sewage sludge, and liquid
manure is common practice in
agriculture around the world.
Due to those applications
heavy metals such as lead
(Pb), mercury (Hg), cadmium
(Cd), copper (Cu), zinc (Zn),
chromium (Cr), and nickel
(Ni) are transferred to arable
soil. Because of its
bactericidal and fungicidal
properties, Cu-containing
pesticides are applied in
organic and conventional
agriculture. Furthermore,
metals such as iron (Fe),
cobalt (Co), manganese (Mn),
copper (Cu), and zinc (Zn) are
applied as nutritional
additives, antimicrobial, and
anti-fouling agents in animal
feed for livestock farming and
fish production.
Resistance to Heavy Metals
Similar to the development of
antimicrobial resistance to
antibiotics, development of
resistance to high levels of
metal has been widely
described as well. To avoid
cellular damage caused by
metal ions, bacteria evolved
mechanisms of metal
tolerance that can be
attributed to three
mechanisms: (i) biosorption
of toxic metals by cell
membrane, cell wall, and
extracellular polymeric
substance of biofilms making
the bacteria belonging to the
biofilm more tolerant to metal
ions, (ii) detoxification
through reduction of
intracellular enzymes such as
mercury reductase which
reduces Hg2+ to the less toxic
Hg0, and (iii) exclusion of
ions by efflux pump.
Since the 1970s, there has
been great concern of about
heavy metal selecting
indirectly for antibiotic
resistance by co-selection.
This indirect selection process
is due to a coupling of the
resistance mechanisms against
antibiotics and heavy metals.
As an example, Aeromonas
salmonicida subsp.
salmonicida isolated from
Atlantic salmon (Salmo salar)
from aquaculture facilities
was identified carrying
mercury and multiple
antibiotic resistance genes
(McIntosh et al., 2008). This
was the first finding of
plasmid associated resistance
to florfenicol, an antibiotic
commonly used to treat
furunculosis in aquacultures.
In essence, studies
investigating co-selection in
the environment frequently
show the correlation of
increased heavy metal
concentrations with increased
phenotypic or genotypic
antibiotic resistance.
Summary
The purpose of this article is
to highlight commonly
addressed concerns and
measures to counter antibiotic
resistance such as (i)
increased infection control
measures, (ii) judicial use of
antibiotics and metallic
compounds, and (iii) patient
screening and isolation. These
are just a percentage of what
is clearly of much larger
scope.
Andre Hsiung
Santa Maria, CA
This article is a summary of Seiler C., and
Berendonk T., (2012). “Heavy metal driven
co-selection of antibiotic resistance in soil
and water bodies impacted by agriculture
and aquaculture. ”Frontiers in Microbiology.
V3, 1-10.