Data for: Copper ions inhibit pentose phosphate pathway function in Staphylococcus aureus

To gain a better insight of how Cu ions toxify cells, metabolomic analyses
were performed in S. aureus strains that lack the described Cu ion
detoxification systems (ΔcopBL ΔcopAZ; cop-). Exposure of the cop- strain
to Cu(II) resulted in an increase in the concentrations of metabolites
utilized to synthesize phosphoribosyl diphosphate (PRPP). PRPP is created
using the enzyme phosphoribosylpyrophosphate synthetase (Prs) which
catalyzes the interconversion of ATP and ribose 5-phosphate to PRPP and
AMP. Supplementing growth medium with metabolites requiring PRPP for
synthesis improved growth in the presence of Cu(II). A suppressor screen
revealed that a strain with a lesion in the gene coding adenine
phosphoribosyltransferase (apt) was more resistant to Cu. Apt catalyzes
the conversion of adenine with PRPP to AMP. The apt mutant had an
increased pool of adenine suggesting that the PRPP pool was being
redirected. Over-production of apt, or alternate enzymes that utilize
PRPP, increased sensitivity to Cu(II). Increasing or decreasing expression
of prs resulted in decreased and increased sensitivity to growth in the
presence of Cu(II), respectively. We demonstrate that Prs is inhibited by
Cu ions in vivo and in vitro and that treatment of cells with Cu(II)
results in decreased PRPP levels. Lastly, we establish that S. aureus that
lacks the ability to remove Cu ions from the cytosol is defective in
colonizing the airway in a murine model of acute pneumonia, as well as the
skin. The data presented are consistent with a model wherein Cu ions
inhibits pentose phosphate pathway function and are used by the immune
system to prevent S. aureus infections.