Copper Toxicity

Brass Alloys: Copper-Bottomed Solutions against Hospital-Acquired Infections?

“…Also, Zheng et al [ 18 ] reported that CuSO 4 in solution was less effective in killing Candida albicans planktonic or biofilm cells than copper ions released from the surface of coupons, implying that direct contact was instrumental in the killing process [ 18 ]. A few years later, Solioz proposed a 4-step chronological order for contact killing by copper-containing surfaces [ 19 ]. The first and crucial step consists in the dissolution of copper ions from the surface and their accumulation in the small aqueous space between the material surface and bacterial membrane, reaching the mM range [ 19 , 20 ].…”

“…A few years later, Solioz proposed a 4-step chronological order for contact killing by copper-containing surfaces [ 19 ]. The first and crucial step consists in the dissolution of copper ions from the surface and their accumulation in the small aqueous space between the material surface and bacterial membrane, reaching the mM range [ 19 , 20 ]. These copper ions can lead to (i) the generation of reactive oxygen species (ROS) [ 21 ], (ii) the inhibition of the respiratory chain [ 22 ], (iii) lipid peroxidation [ 23 , 24 ] damages to cell membrane [ 24 , 25 , 26 , 27 ], (iv) DNA degradation [ 28 , 29 ], (v) modified protein expression [ 30 ], and (vi) displacement of iron-sulfur clusters and inactivation of metalloproteins [ 31 , 32 ] ( Figure 1 ).…”

Cytosolic Copper Binding by a Bacterial Storage Protein and Interplay with Copper Efflux

“…This is consistent with the sites that can cause toxicity in Δ copA E. coli at 1 mM Cu having Cu(I) affinities tighter than those of Csp3s (average values of (1−2) × 10 17 M −1 have been measured for Csp3s [2]), with the ability of Bs Csp3 to acquire Cu(I) being driven by the large amount of protein present. The locations of all sites that can result in bacterial Cu toxicity remain to be determined, although Fe-S cluster-containing proteins are currently the main target identified [8,9,10,11,12,13], and these would be expected to be able to bind Cu(I) tightly. Some Cu(I) may reside in cytosolic pools bound by a highly-abundant species such as glutathione (GSH) that has been implicated in Cu(I) handling in E. coli [41], although a role in toxicity is currently unclear [8,9].…”

“…The locations of all sites that can result in bacterial Cu toxicity remain to be determined, although Fe-S cluster-containing proteins are currently the main target identified [8,9,10,11,12,13], and these would be expected to be able to bind Cu(I) tightly. Some Cu(I) may reside in cytosolic pools bound by a highly-abundant species such as glutathione (GSH) that has been implicated in Cu(I) handling in E. coli [41], although a role in toxicity is currently unclear [8,9]. The abundance of GSH in E. coli [44,45], along with its affinity for Cu(I) [46], is consistent with a Csp3 being able to compete with it for cuprous ions.…”

“…The safe handling of Cu is particularly problematic in the reducing cytosol as Cu(I) can be highly toxic if not carefully regulated [8,9]. For many years this has been associated with reactive oxygen species formation, but more recently it has become clear that a major mechanism of toxicity is driven by the ability of Cu(I) to readily displace, or bind at locations for, the native cofactor in other metalloproteins, probably driven by its higher affinities for these sites [10].…”