Abstract
Copper is an essential cofactor of various enzymes, but free copper is highly toxic to living cells. To maintain cellular metabolism at different ambient copper concentrations, bacteria have evolved specific copper homeostasis systems that mostly act as defence mechanisms. As well as under free-living conditions, copper defence is critical for virulence in pathogenic bacteria. Most bacteria synthesize P-type copper export ATPases as principal defence determinants when copper concentrations exceed favourable levels. In addition, many bacteria utilize resistance-nodulation-cell division (RND)-type efflux systems and multicopper oxidases to cope with excess copper. This review summarizes our current knowledge on copper-sensing transcriptional regulators, which we assign to nine different classes. Widespread one-component regulators are CueR, CopY and CsoR, which were initially identified in Escherichia coli, Enterococcus hirae and Mycobacterium tuberculosis, respectively. CueR activates homeostasis gene expression at elevated copper concentrations, while CopY and CsoR repress their target genes under copper-limiting conditions. Besides these one-component systems, which sense the cytoplasmic copper status, many Gram-negative bacteria utilize two-component systems, which sense periplasmic copper concentrations. In addition to these well-studied transcriptional factors, copper control mechanisms acting at the post-transcriptional and the post-translational levels will be discussed.
Highlights
Biological evolution started at a time when copper mostly existed in the form of water-insoluble chemical compounds not utilizable for living cells (Rensing & Grass, 2003)
Copper is highly toxic to living cells, as it interacts with free proteinogenic thiol groups, destabilizes iron–sulfur cofactors, competes with other metals for protein binding sites, and possibly leads to formation of reactive oxygen species (Chillappagari et al, 2010; Hiniker et al, 2005; Macomber & Imlay, 2009)
Disturbance of copper homeostasis is thought to lead to human diseases such as Alzheimer’s disease, Parkinson’s disease, Wilson’s disease and Menkes syndrome (Barnham & Bush, 2008; Lenartowicz et al, 2011; Lutsenko, 2010)
Summary
Biologie der Mikroorganismen, Fakultat fur Biologie und Biotechnologie, Ruhr-Universitat Bochum, 44780 Bochum, Germany. To maintain cellular metabolism at different ambient copper concentrations, bacteria have evolved specific copper homeostasis systems that mostly act as defence mechanisms. CueR activates homeostasis gene expression at elevated copper concentrations, while CopY and CsoR repress their target genes under copperlimiting conditions. Besides these one-component systems, which sense the cytoplasmic copper status, many Gram-negative bacteria utilize two-component systems, which sense periplasmic copper concentrations. In addition to these well-studied transcriptional factors, copper control mechanisms acting at the post-transcriptional and the post-translational levels will be discussed
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