Identification of the main glutamine and glutamate transporters in Staphylococcus aureus and their impact on c-di-AMP production |
| |
Authors: | Merve S Zeden Igor Kviatkovski Christopher F Schuster Vinai C Thomas Paul D Fey Angelika Gründling |
| |
Institution: | 1. Section of Molecular Microbiology, Medical Research Council Centre for Molecular Bacteriology and Infection, Imperial College London, London, UK;2. Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA |
| |
Abstract: | 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. |
| |
Keywords: | AlsT amino acid transport c-di-AMP GltS glutamate transporter glutamine transporter OpuD osmolyte transport Staphylococcus aureus |
|
|