Identification of the main glutamine and glutamate transporters in Staphylococcus aureus and their impact on c-di-AMP production

Merve S. Zeden, Igor Kviatkovski, Christopher F. Schuster, Vinai C. Thomas, Paul D. Fey, Angelika Gründling

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


A Staphylococcus aureus strain deleted for the c-di-AMP cyclase gene dacA is unable to survive in rich medium unless it acquires compensatory mutations. Previously identified mutations were in opuD, encoding the main glycine-betaine transporter, and alsT, encoding a predicted amino acid transporter. Here, we show that inactivation of OpuD restores the cell size of a dacA mutant to near wild-type (WT) size, while inactivation of AlsT does not. AlsT was identified as an efficient glutamine transporter, indicating that preventing glutamine uptake in rich medium rescues the growth of the S. aureus dacA mutant. In addition, GltS was identified as a glutamate transporter. By performing growth curves with WT, alsT and gltS mutant strains in defined medium supplemented with ammonium, glutamine or glutamate, we revealed that ammonium and glutamine, but not glutamate promote the growth of S. aureus. This suggests that besides ammonium also glutamine can serve as a nitrogen source under these conditions. Ammonium and uptake of glutamine via AlsT and hence likely a higher intracellular glutamine concentration inhibited c-di-AMP production, while glutamate uptake had no effect. These findings provide, besides the previously reported link between potassium and osmolyte uptake, a connection between nitrogen metabolism and c-di-AMP signalling in S. aureus.

Original languageEnglish (US)
Pages (from-to)1085-1100
Number of pages16
JournalMolecular Microbiology
Issue number6
StatePublished - Jun 1 2020


  • AlsT
  • GltS
  • OpuD
  • Staphylococcus aureus
  • amino acid transport
  • c-di-AMP
  • glutamate transporter
  • glutamine transporter
  • osmolyte transport

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology


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