Inactivation of the Pta-AckA pathway causes cell death in staphylococcus aureus

Marat R. Sadykov, Vinai Chittezham Thomas, Darrell D. Marshall, Christopher J. Wenstrom, Derek E. Moormeier, Todd J. Widhelm, Austin S Nuxoll, Robert Powers, Kenneth W Bayles

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

During growth under conditions of glucose and oxygen excess, Staphylococcus aureus predominantly accumulates acetate in the culture medium, suggesting that the phosphotransacetylase-acetate kinase (Pta-AckA) pathway plays a crucial role in bacterial fitness. Previous studies demonstrated that these conditions also induce the S. aureus CidR regulon involved in the control of cell death. Interestingly, the CidR regulon is comprised of only two operons, both encoding pyruvate catabolic enzymes, suggesting an intimate relationship between pyruvate metabolism and cell death. To examine this relationship, we introduced ackA and pta mutations in S. aureus and tested their effects on bacterial growth, carbon and energy metabolism, cid expression, and cell death. Inactivation of the Pta-AckA pathway showed a drastic inhibitory effect on growth and caused accumulation of dead cells in both pta and ackA mutants. Surprisingly, inactivation of the Pta-AckA pathway did not lead to a decrease in the energy status of bacteria, as the intracellular concentrations of ATP, NAD+, and NADH were higher in the mutants. However, inactivation of this pathway increased the rate of glucose consumption, led to a metabolic block at the pyruvate node, and enhanced carbon flux through both glycolysis and the tricarboxylic acid (TCA) cycle. Intriguingly, disruption of the Pta-AckA pathway also induced the CidR regulon, suggesting that activation of alternative pyruvate catabolic pathways could be an important survival strategy for the mutants. Collectively, the results of this study demonstrate the indispensable role of the Pta-AckA pathway in S. aureus for maintaining energy and metabolic homeostasis during overflow metabolism.

Original languageEnglish (US)
Pages (from-to)3035-3044
Number of pages10
JournalJournal of bacteriology
Volume195
Issue number13
DOIs
StatePublished - Jul 16 2013

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Phosphate Acetyltransferase
Acetate Kinase
Staphylococcus aureus
Cause of Death
Pyruvic Acid
Cell Death
Regulon
NAD
Growth
Carbon Cycle
Glucose
Citric Acid Cycle
Glycolysis
Operon
Energy Metabolism
Culture Media
Acetates
Homeostasis
Carbon
Adenosine Triphosphate

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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Inactivation of the Pta-AckA pathway causes cell death in staphylococcus aureus. / Sadykov, Marat R.; Chittezham Thomas, Vinai; Marshall, Darrell D.; Wenstrom, Christopher J.; Moormeier, Derek E.; Widhelm, Todd J.; Nuxoll, Austin S; Powers, Robert; Bayles, Kenneth W.

In: Journal of bacteriology, Vol. 195, No. 13, 16.07.2013, p. 3035-3044.

Research output: Contribution to journalArticle

Sadykov, Marat R. ; Chittezham Thomas, Vinai ; Marshall, Darrell D. ; Wenstrom, Christopher J. ; Moormeier, Derek E. ; Widhelm, Todd J. ; Nuxoll, Austin S ; Powers, Robert ; Bayles, Kenneth W. / Inactivation of the Pta-AckA pathway causes cell death in staphylococcus aureus. In: Journal of bacteriology. 2013 ; Vol. 195, No. 13. pp. 3035-3044.
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AU - Marshall, Darrell D.

AU - Wenstrom, Christopher J.

AU - Moormeier, Derek E.

AU - Widhelm, Todd J.

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AU - Powers, Robert

AU - Bayles, Kenneth W

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