TY - JOUR
T1 - The Ktr potassium transport system in Staphylococcus aureus and its role in cell physiology, antimicrobial resistance and pathogenesis
AU - Gries, Casey M.
AU - Bose, Jeffrey L.
AU - Nuxoll, Austin S.
AU - Fey, Paul D.
AU - Bayles, Kenneth W.
PY - 2013/8
Y1 - 2013/8
N2 - 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 aureusKtr 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 0.1mM 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. aureusKtr 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.
AB - 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 aureusKtr 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 0.1mM 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. aureusKtr 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.
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U2 - 10.1111/mmi.12312
DO - 10.1111/mmi.12312
M3 - Article
C2 - 23815639
AN - SCOPUS:84881543908
SN - 0950-382X
VL - 89
SP - 760
EP - 773
JO - Molecular Microbiology
JF - Molecular Microbiology
IS - 4
ER -