Biocidal Mechanisms of Metallic Copper Surfaces - Use of Biocidal Surfaces for Reduction of Healthcare Acquired Infections - page 127

6.4 Holistic “Systems View” of Biocidal Effect
of Metallic Copper
There are multiple interrelated molecular factors that play a role during bacterial
killing by dry exposure to copper surfaces. When cells get in contact with copper
surfaces, copper ions are dissolved from the surface leading to the first steps of cell
damage [ 25 , 27 , 61 , 72 ]. The presence of copper ions and ROS stress induces
toxicity to the membranes, leading to loss of membrane structure (Esp´rito Santo,
Bleichert and Grass, unpublished results, [ 27 , 28 , 39 , 72 ]). In a recent study by [ 53 ],
it was suggested that the major factor that causes cellular damage is the surface
ability to generate Cu(I). Further cell damage is induced by copper ions and ROS
generation affecting other cellular biomolecules, such as proteins [ 63 ]. After cell
death, genomic and plasmid DNA become degraded [ 27 , 39 ]. This mechanism
supports the view of the chain of events that lead to cell inactivation by copper
surfaces proposed by Grass, Rensing and Solioz [ 35 ] (Fig. 6.17 ).
When cells are applied on a dry metallic copper surface, copper ions are rapidly
released and high quantities are quickly accumulated by cells, as outlined by the
copper quantification assays in the data published by [ 27 , 28 , 72 ]. Simultaneously,
generation of ROS occurs, as evidenced by protective effects of ROS quenchers
[ 25 , 86 ] and by ROS fluorescent indicators [ 72 ]. As a consequence, these two
related events (copper and ROS generation) induce toxicity and damage cellular
components. Indeed, membranes are the first component to be damaged by copper
surface toxicity as observed by the Live/Dead ™ experiments [ 27 , 28 , 72 ]. Present
evidences indicate that membranes are damaged due to lipid peroxidation [ 39 ]. Con-
sequently, when lipid oxidation reaches an overwhelming level, the process
becomes lethal for the cells. Thus, cells become inactivated by the damage inflicted
on the membranes, which then leads to loss of membrane potential [ 72 , 86 ] and
likely release of cytoplasmic contents. Finally, continuous presence of copper leads
to further ROS production which induces further damage to various biomolecules,
Fig. 6.17 Representation of the chain of events in contact killing. (a) Cells enter in contact with
the surface; copper is released causing cellular damage. (b) Cell membrane becomes permeable
due to copper and other stress, leading to loss of membrane potential and cytoplasmic content.
(c) Generation of reactive oxygen species is provoked by copper ions, which cause further cell
damage. (d) cellular DNA becomes degraded [ 35 ]