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Significance Bacteria utilize sensory signal transduction systems to constantly survey and respond to changes in their environment. The human pathogenStaphylococcus aureus uses two-component signaling systems to sense its surroundings and adapt to hostile stresses of the host in part by shifting its metabolism. Here, we sought to understand how theS .aureus SrrAB two-component system senses changes in its environment during an infection. Using biophysical and biochemical approaches and in vivo experiments, we identified a mechanism by which the SrrB sensor histidine kinase detects a shift in its metabolism that occurs during an infection. Our findings provide general insight into the mechanisms by which bacterial histidine kinases sense environmental cues to regulate signal transduction and pathogenicity.

The SrrAB two-component system regulates Staphylococcus aureus pathogenicity through redox sensitive cysteines