Temporal control of Staphylococcus aureus intracellular pH by sodium and potassium

Adaptation to environmental change during both colonization and infection is essential to the pathogenesis of Staphylococcus aureus. Like other bacterial pathogens that require potassium to fulfill nutritional and chemiosmotic requirements, S. aureus has been shown to utilize potassium transport to modulate virulence gene expression, antimicrobial resistance, and osmotic tolerance. Recent studies examining the role for potassium uptake in mediating S. aureus physiology have also described its contribution in mediating carbon flux within central metabolism and generation of a proton motive force. Here, we utilize a pH-sensitive green fluorescent protein to examine the temporal regulation of S. aureus intracellular pH by potassium and sodium under various environmental conditions, including extracellular pH and antibiotic stress. Our results distinguish unique conditions and transport mechanisms that utilize these ions to modulate cytoplasmic pH homeostasis, and they identify these processes as a novel mechanism of intrinsic ampicillin resistance in S. aureus.