Response of Gram-positive bacteria to copper stress

Abstract

The Gram-positive bacteria Enterococcus hirae, Lactococcus lactis, and Bacillus subtilis have received wide attention in the study of copper homeostasis. Consequently, copper extrusion by ATPases, gene regulation by copper, and intracellular copper chaperoning are understood in some detail. This has provided profound insight into basic principles of how organisms handle copper. It also emerged that many bacterial species may not require copper for life, making copper homeostatic systems pure defense mechanisms. Structural work on copper homeostatic proteins has given insight into copper coordination and bonding and has started to give molecular insight into copper handling in biological systems. Finally, recent biochemical work has shed new light on the mechanism of copper toxicity, which may not primarily be mediated by reactive oxygen radicals.

Bacterial copper storage proteins

“…A role for these proteins in Cu(I) storage is currently the most logical suggestion for their function, but in many cases what they are storing Cu for remains unknown. The presence of bacterial Cu storage proteins seems consistent with a number of other observations: (1) that bacterial Cu-import systems exist (6,7,17,21,52,56,77,95), including into the cytosol; (2) that endogenous pools of the metal are available in bacteria (11,15,16,18,96); and (3) that E. coli grown in both LB and minimal medium accumulates Cu (97). It also highlights that there are alternative mechanisms to using different cellular compartments to prevent mis-metallation of proteins by Cu (37).…”

“…Copper homeostasis has been extensively investigated in certain Csp3-possessing non-methanotrophs, with probably the best example being Bacillus subtilis (21,28,68,76,77). Therefore, the Csp3 from this model Gram positive bacterium has been studied in vitro (36).…”

“…A well-characterized family of Cu-homeostasis proteins are the Cu-transporting Ptype ATPases, which can remove this metal ion from the cytosol (4)(5)(6)(7)(20)(21)(22)(23)(24). In eukaryotes, these Cu-efflux pumps work with a cytosolic Cu metallochaperone (the well-characterized ATOX1 in humans and Atx1 in yeast) to facilitate import into the trans-Golgi network for secreted Cu enzymes (4,5,19,24,25).…”

Copper-responsive gene regulation in bacteria

“…hirae CopY is the founding member of a copper-responsive repressor family belonging to the superfamily of HTH regulators (Odermatt & Solioz, 1995;Solioz et al, 2010) (Table 1). CopY-type regulators are widespread in Gram-positive bacteria, but apparently absent in Gramnegative species (Liu et al, 2007) (Table 2).…”

Non-enzymic copper reduction by menaquinone enhances copper toxicity in Lactococcus lactis IL1403

“…Inside the cell, specialized proteins are responsible for copper handling, such as insertion into cuproenzymes or delivery to copper-responsive regulators [for recent reviews, see Solioz et al (2010) and Magnani & Solioz (2007)]. To the extent it has been studied, these copper homeostatic proteins bind Cu + and it is generally assumed that Cu + prevails in the reducing environment of the cytoplasm, without the need for a copper reductase (Solioz et al, 2011).…”