Death by Cystine: an Adverse Emergent Property from a Beneficial Series of Reactions

In this issue of the Journal of Bacteriology, Chonoles Imlay et al. (K. R. Chonoles Imlay, S. Korshunov, and J. A. Imlay, J Bacteriol 197:3629-3644, 2015, http://dx.doi.org/10.1128/JB.00277-15) show that oxidative stress kills sulfur-restricted Escherichia coli grown with sublethal H2O2 when challenged with cystine. Killing requires rapid and seemingly unregulated cystine transport and equally rapid cystine reduction to cysteine. Cysteine export completes an energy-depleting futile cycle. Each reaction of the cycle could be beneficial. Together, a cystine-mediated vulnerability emerges during the transition from a sulfur-restricted to a sulfur-replete environment, perhaps because of complexities of sulfur metabolism.