Gold and copper sensory and detoxification systems in bacteria

ESPARIZ, M.; PÉREZ AUDERO, M. E.; CHECA, S. K.; SONCINI, F. C.

Janelia Farm Research Campus, Ashburn, V.A., EEUU

Congreso; 2006 Meeting of the Howard Hughes Medical Institute International Research Scholars; 2006

Howard Hughes Medical Institute

Bacteria are able to resist a wide variety of transition metals, including harmful non-essential elements, such as Hg, Ag, Cd, Cr, and Pb, and essential nutrients such as Fe, Cu, Zn, Ni, Mo, Mn, and Co, that become toxic at high intracellular concentrations.  Metal-dependent transcriptional regulatory systems are the major cellular mechanism employed to control intracellular homeostasis of essential metal ions, and detoxification of harmful non-essential transition elements.  A subject of increasing interest in the field is to understand how these metalloregulatory systems are able to differentiate between metal ions in order to trigger the proper response without affecting the homeostasis of related transition elements.  Here we characterize a Salmonella-specific metalloregulator, GodS, that stimulates the expression of genes required for gold resistance when traces of AuHCl4 are present in the culture medium.  GodS shares homology with CueR, the enterobacterial copper-resistance regulator.  Both proteins harbor a C-terminal metal-binging motif that defines the +1 ion-binding subclass of the MerR-family of transcriptional regulators.  However, GodS is 53.4 times more sensitive to gold than to copper, in contrast to CueR that shows essentially the same affinity for both ions.  Moreover, we establish that subtle differences within the metal-binding motif account for metal-selectivity.  A GodS chimeric regulator in which this motif is replaced by its CueR-counterpart acquires the CueR-metal responsiveness.  Homology between GodS and CueR is also extended to their target promoter recognition sites, and cross-activation occurs in strains deleted in either regulatory gene, suggesting that differences in nucleotide bases are responsible for the regulator’s promoter discrimination.  Collectively, these results indicate that these systems are evolutionary and functionally linked to endow bacteria with resistance to group-1B transition metals, and suggest that GodS has gained gold-selectivity from a common ancestor.