The Ktr potassium transport system in Staphylococcus aureus and its role in cell physiology, antimicrobial resistance...

Potassium (K(+) ) plays a vital role in bacterial physiology, including regulation of cytoplasmic pH, turgor pressure and transmembrane electrical potential. Here, we examine the Staphylococcus aureus Ktr system uniquely comprised of two ion-conducting proteins (KtrB and KtrD) and only one regulator (KtrA). Growth of Ktr system mutants was severely inhibited under K(+) limitation, yet detectable after an extended lag phase, indicating the presence of a secondary K(+) transporter. Disruption of both ktrA and the Kdp-ATPase system, important for K(+) uptake in other organisms, eliminated regrowth in 0.1 mM K(+) , demonstrating a compensatory role for Kdp to the Ktr system. Consistent with K(+) transport mutations, S. aureus devoid of the Ktr system became sensitive to hyperosmotic conditions, exhibited a hyperpolarized plasma membrane, and increased susceptibility to aminoglycoside antibiotics and cationic antimicrobials. In contrast to other organisms, the S. aureus Ktr system was shown to be important for low-K(+) growth under alkaline conditions, but played only a minor role in neutral and acidic conditions. In a mouse competitive index model of bacteraemia, the ktrA mutant was significantly outcompeted by the parental strain. Combined, these results demonstrate a primary mechanism of K(+) uptake in S. aureus and a role for this system in pathogenesis.