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

Casey M. Gries, Jeffrey L. Bose, Austin S Nuxoll, Paul D Fey, Kenneth W Bayles

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)760-773
Number of pages14
JournalMolecular Microbiology
Volume89
Issue number4
DOIs
StatePublished - Aug 1 2013

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Cell Physiological Phenomena
Staphylococcus aureus
Potassium
Bacterial Physiological Phenomena
Aminoglycosides
Growth
Bacteremia
Staphylococcus
Membrane Potentials
Adenosine Triphosphatases
Cell Membrane
Ions
Anti-Bacterial Agents
Pressure
Mutation
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Microbiology

Cite this

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abstract = "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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AU - Bayles, Kenneth W

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