Redox Imbalance Underlies the Fitness Defect Associated with Inactivation of the Pta-AckA Pathway in Staphylococcus aureus

Darrell D. Marshall, Marat R. Sadykov, Vinai C. Thomas, Kenneth W. Bayles, Robert Powers

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

The phosphotransacetylase-acetate kinase (Pta-AckA) pathway is thought to be a vital ATP generating pathway for Staphylococcus aureus. Disruption of the Pta-AckA pathway during overflow metabolism causes significant reduction in growth rate and viability, albeit not due to intracellular ATP depletion. Here, we demonstrate that toxicity associated with inactivation of the Pta-AckA pathway resulted from an altered intracellular redox environment. Growth of the pta and ackA mutants under anaerobic conditions partially restored cell viability. NMR metabolomics analyses and 13C6-glucose metabolism tracing experiments revealed the activity of multiple pathways that promote redox (NADH/NAD+) turnover to be enhanced in the pta and ackA mutants during anaerobic growth. Restoration of redox homeostasis in the pta mutant by overexpressing l- lactate dehydrogenase partially restored its viability under aerobic conditions. Together, our findings suggest that during overflow metabolism, the Pta-AckA pathway plays a critical role in preventing cell viability defects by promoting intracellular redox homeostasis.

Original languageEnglish (US)
Pages (from-to)1205-1212
Number of pages8
JournalJournal of proteome research
Volume15
Issue number4
DOIs
StatePublished - Apr 1 2016

Keywords

  • NMR
  • Pta-AckA pathway
  • Staphylococcus aureus
  • metabolomics
  • redox imbalance

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

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