Biocidal Mechanisms of Metallic Copper Surfaces - Use of Biocidal Surfaces for Reduction of Healthcare Acquired Infections - page 108

In addition to these chromosome-encoded genes, Gram-negative bacteria pos-
sess plasmid-encoded copper resistances. The best studied is the plasmid-encoded
copper resistance determinant, Pco system of plasmid pRJ1004, isolated from
E. coli present in the gut flora of pigs fed with a diet supplemented with copper
sulphate as a growth promotant [ 5 ]. This plasmid encodes seven genes,
pcoABCDRSE , whose expression is dependent on copper and is accomplished by
PcoRS [ 5 ]: PcoA is a multicopper oxidase related to CueO, PcoC and PcoE are two
periplasmic copper chaperones, and PcoB and PcoD have unknown functions.
Among Gram-positive bacteria, Lactococcus lactis , Bacillus subtilis , and
Enterococcus hirae are the best studied organisms on copper homeostasis with
E. hirae being the model organism for metal handling [ 81 ]. In this organism an
operon of four genes, copYZAB , is responsive to copper stress. Free cytoplasmic
Cu(I) binds to CopY (a copper-responsive repressor) resulting in derepression
of the cop operon. Start of transcription results in increased production of CopY,
copper chaperone CopZ, and the Cu(I)-translocating P 1B -ATPases, CopA and
CopB (Fig. 6.1 )[ 69 ], followed by Cop B-promoted extrusion of excess of copper
and silver from the cytoplasm [ 80 ]. On the other hand, the function of CopA is still
unclear, but it might function as an efflux system for copper incorporation into
enzymes such as cytochrome oxidases [ 2 , 73 ].
The ability of L. lactis to withstand copper released from traditional Swiss
cheese copper vats ignited renewed interest in studying copper homeostasis in
this bacterium. The mechanism of coping with high copper concentrations in
L. lactis is similar to E. hirae and includes a copper-inducible operon, copRZA ,
where CopR is a CopY-type repressor, CopZ is a copper chaperone, and CopA is a
copper export ATPase. CopB is encoded separately and repressed by CopR, but its
copper export function has not been determined yet [ 82 ].
The inability of bacterial cells to expel copper when its concentration rises above
a certain threshold leads to accumulation of free copper in cells, which, in turn,
causes damage to multiple biomolecules. The next section will discuss mechanisms
of copper toxicity.

6.2.4 Ionic Copper Toxicity

Organisms did not develop copper specific resistance mechanisms in vain; excess of
this metal is very toxic to cells. Copper is ranked fifth among the most toxic of
seventeen metals to soil bacteria, preceded by silver, mercury, chromium, and
cadmium [ 20 ]. Furthermore, copper was found to be one of the most toxic metals
to heterotrophic bacteria in aquatic environments [ 1 ], where metal-salt sensitivity
of aqueous microflora was higher when exposed to: Ag Cu, Ni Ba, Cr,

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Hg Zn, Pb, Na, Cd. Copper is capable of forming stable complexes with a wide

variety of ligands regardless of its valence state, thus, it binds easily to biomole-
cules such as proteins, lipids, and nucleic acids [ 32 ].

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